Methods and compositions for treatment of pain using capsaicin

Abstract

The invention provides methods and compositions for treatment of pain, such as joint pain, using capsaicin in a procedure that attenuates transient burning sensation experienced by patients due to capsaicin administration. The methods desirably provide relief from joint pain, such as osteoarthritic knee joint pain, for an extended duration, such as at least about 3 months, 6 months, 9 months, or 1 year. To attenuate the adverse side effect of a transient burning sensation caused by capsaicin-induced neuronal excitation, the methods utilize a cooling article, such as a material wrap cooled via a circulating fluid, to reduce the temperature of tissue to be exposed to capsaicin to within a certain range for certain durations of time, optionally in combination with administering a local anesthetic agent, resulting in the substantial reduction or even elimination of transient burning sensation caused by capsaicin.

1 . A method of ameliorating osteoarthritic knee joint pain in a human patient, comprising:
 a. applying for a duration of about 15 minutes a cooling article to an exterior surface of a human patient's knee presenting with osteoarthritic knee joint pain, wherein the cooling article has an exterior surface temperature in the range of from about 5° C. to about 15° C. for application to the exterior surface of said knee; then   b. administering by injection into the intra-articular space of the joint of said knee a pharmaceutical composition comprising a single pain-relief agent selected from the group consisting of lidocaine and a pharmaceutically acceptable salt thereof, in order to deliver a dose of lidocaine in an amount ranging from about 0.1 g to about 0.5 g; then   c. applying for a duration of about 30 minutes a cooling article to an exterior surface of said knee, wherein the cooling article has an exterior surface temperature in the range of from about 5° C. to about 15° C. for application to the exterior surface of said knee; then   d. administering by injection into the intra-articular space of the joint of said knee a pharmaceutical composition comprising capsaicin in order to deliver a dose of capsaicin in an amount of about 1 mg; and then   e. applying a cooling article to an exterior surface of said knee for a duration of at least about 30 minutes, wherein the cooling article has an exterior surface temperature in the range of from about 5° C. to about 15° C. for application to the exterior surface of said knee;
 to thereby ameliorate osteoarthritic knee joint pain in the human patient. 
   
     
     
         2 . A method of attenuating transient burning sensation due to injection of capsaicin into a human osteoarthritic knee joint, comprising:
 a. applying for a duration of about 15 minutes a cooling article to an exterior surface of a human patient's knee presenting with osteoarthritic knee joint pain, wherein the cooling article has an exterior surface temperature in the range of from about 5° C. to about 15° C. for application to the exterior surface of said knee; then   b. administering by injection into the intra-articular space of the joint of said knee a pharmaceutical composition comprising a single pain-relief agent selected from the group consisting of lidocaine and a pharmaceutically acceptable salt thereof, in order to deliver a dose of lidocaine in an amount ranging from about 0.1 g to about 0.5 g; then   c. applying for a duration of about 30 minutes a cooling article to an exterior surface of said knee, wherein the cooling article has an exterior surface temperature in the range of from about 5° C. to about 15° C. for application to the exterior surface of said knee; then   d. administering by injection into the intra-articular space of the joint of said knee a pharmaceutical composition comprising capsaicin in order to deliver a dose of capsaicin in an amount of about 1 mg; and then   e. applying a cooling article to an exterior surface of said knee for a duration of at least about 30 minutes, wherein the cooling article has an exterior surface temperature in the range of from about 5° C. to about 15° C. for application to the exterior surface of said knee;
 to thereby attenuate transient burning sensation due to injection of capsaicin. 
   
     
     
         3 . The method of  claim 1  or  2 , wherein after administration of the pharmaceutical composition comprising capsaicin in step (d) but prior to step (e) said knee is flexed. 
     
     
         4 . The method of  claim 1  or  2 , wherein after administration of the pharmaceutical composition comprising capsaicin in step (d) but prior to step (e) said knee is flexed about 5 times. 
     
     
         5 . The method of any one of  claims 1 - 4 , wherein the cooling article has an exterior surface temperature in the range of from about 6° C. to about 13° C. for application to the exterior surface of said knee. 
     
     
         6 . The method of any one of  claims 1 - 4 , wherein the cooling article has an exterior surface temperature in the range of from about 7° C. to about 13° C. for application to the exterior surface of said knee. 
     
     
         7 . The method of any one of  claims 1 - 4 , wherein the cooling article has an exterior surface temperature in the range of from about 7° C. to about 10° C. for application to the exterior surface of said knee. 
     
     
         8 . The method of any one of  claims 1 - 4 , wherein the cooling article has an exterior surface temperature in the range of from about 5° C. to about 10° C. for application to the exterior surface of said knee. 
     
     
         9 . The method of any one of  claims 1 - 4 , wherein the cooling article has an exterior surface temperature in the range of from about 8° C. to about 10° C. for application to the exterior surface of said knee 
     
     
         10 . The method of any one of  claims 1 - 4 , wherein the cooling article has an exterior surface temperature in the range of from about 6° C. to about 8° C. for application to the exterior surface of said knee. 
     
     
         11 . The method of any one of  claims 1 - 4 , wherein the cooling article has an exterior surface temperature in the range of from about 5° C. to about 8° C. for application to the exterior surface of said knee. 
     
     
         12 . The method of any one of  claims 1 - 4 , wherein the cooling article has an exterior surface temperature in the range of from about 5° C. to about 7° C. for application to the exterior surface of said knee. 
     
     
         13 . The method of any one of  claims 1 - 4 , wherein the cooling article has an exterior surface temperature of about 12° C. for application to the exterior surface of said knee. 
     
     
         14 . The method of any one of  claims 1 - 4 , wherein the cooling article has an exterior surface temperature of about 11° C. for application to the exterior surface of said knee. 
     
     
         15 . The method of any one of  claims 1 - 4 , wherein the cooling article has an exterior surface temperature of about 10° C. for application to the exterior surface of said knee. 
     
     
         16 . The method of any one of  claims 1 - 4 , wherein the cooling article has an exterior surface temperature of about 9° C. for application to the exterior surface of said knee. 
     
     
         17 . The method of any one of  claims 1 - 4 , wherein the cooling article has an exterior surface temperature of about 8° C. for application to the exterior surface of said knee. 
     
     
         18 . The method of any one of  claims 1 - 4 , wherein the cooling article has an exterior surface temperature of about 7° C. for application to the exterior surface of said knee. 
     
     
         19 . The method of any one of  claims 1 - 4 , wherein the cooling article has an exterior surface temperature of about 6° C. for application to the exterior surface of said knee. 
     
     
         20 . The method of any one of  claims 1 - 4  wherein the cooling article has an exterior surface temperature of about 5° C. for application to the exterior surface of said knee. 
     
     
         21 . The method of any one of  claims 1 - 20 , wherein in step (b) the dose of lidocaine is about 0.3 g. 
     
     
         22 . The method of any one of  claims 1 - 20 , wherein in step (b) the dose of lidocaine is 0.3 g. 
     
     
         23 . The method of any one of  claims 1 - 22 , wherein the pharmaceutical composition comprising a single pain-relief agent is an aqueous mixture that contains lidocaine at a concentration of about 2% w/w. 
     
     
         24 . The method of any one of  claims 1 - 23 , wherein the pharmaceutical composition comprising a single pain-relief agent further comprises sodium chloride. 
     
     
         25 . The method of any one of  claims 1 - 23 , wherein the pharmaceutical composition comprising a single pain-relief agent further comprises sodium chloride at a concentration ranging from about 4 mg/mL to about 8 mg/mL. 
     
     
         26 . The method of any one of  claims 1 - 25 , wherein the pharmaceutical composition comprising a single pain-relief agent has a volume in the range of from about 13 mL to about 17 mL. 
     
     
         27 . The method of any one of  claims 1 - 25 , wherein the pharmaceutical composition comprising a single pain-relief agent has a volume of about 15 mL. 
     
     
         28 . The method of any one of  claims 1 - 27 , wherein the pharmaceutical composition comprising capsaicin is an aqueous mixture containing capsaicin. 
     
     
         29 . The method of any one of  claims 1 - 28 , wherein the pharmaceutical composition comprising capsaicin has a volume of about 4 mL. 
     
     
         30 . The method of any one of  claims 1 - 28 , wherein the pharmaceutical composition comprising capsaicin has a volume of about 2 mL. 
     
     
         31 . The method of any one of  claims 1 - 30 , wherein the duration in step (e) is from about 30 minutes to about 90 minutes. 
     
     
         32 . The method of any one of  claims 1 - 30 , wherein the duration in step (e) is from about 30 minutes to about 60 minutes. 
     
     
         33 . The method of any one of  claims 1 - 32 , wherein the dose of capsaicin is 1 mg. 
     
     
         34 . A method of ameliorating osteoarthritic knee joint pain in a human patient, comprising:
 a. applying a cooling article to an exterior surface of a human patient's knee presenting with osteoarthritic knee joint pain; then   b. administering by injection into the intra-articular space of the joint of said knee a pharmaceutical composition comprising a single pain-relief agent selected from the group consisting of lidocaine and a pharmaceutically acceptable salt thereof, in order to deliver a dose of lidocaine in an amount of about 0.1 g to about 0.5 g; then   c. applying a cooling article to an exterior surface of said knee to achieve a temperature in the range of from about 26° C. to about 33° C. for fluid in the intra-articular space of the joint of said knee; then   d. administering by injection into the intra-articular space of the joint of said knee a pharmaceutical composition comprising capsaicin in order to deliver a dose of capsaicin in an amount of about 1 mg; and then   e. applying a cooling article to an exterior surface of said knee;
 to thereby ameliorate osteoarthritic knee joint pain in the human patient. 
   
     
     
         35 . A method of attenuating transient burning sensation due to injection of capsaicin into a human osteoarthritic knee joint, comprising:
 a. applying a cooling article to an exterior surface of a human patient's knee presenting with osteoarthritic knee joint pain; then   b. administering by injection into the intra-articular space of the joint of said knee a pharmaceutical composition comprising a single pain-relief agent selected from the group consisting of lidocaine and a pharmaceutically acceptable salt thereof, in order to deliver a dose of lidocaine in an amount of ranging from about 0.1 g to about 0.5 g; then   c. applying a cooling article to an exterior surface of said knee to achieve a temperature in the range of from about 26° C. to about 33° C. for fluid in the intra-articular space of the joint of said knee; then   d. administering by injection into the intra-articular space of the joint of said knee a pharmaceutical composition comprising capsaicin in order to deliver a dose of capsaicin in an amount of about 1 mg; and then   e. applying a cooling article to an exterior surface of said knee;
 to thereby attenuate transient burning sensation due to injection of capsaicin. 
   
     
     
         36 . The method of  claim 34  or  35 , wherein after administration of the pharmaceutical composition comprising capsaicin in step (d) but prior to step (e) said knee is flexed. 
     
     
         37 . The method of  claim 34  or  35 , wherein after administration of the pharmaceutical composition comprising capsaicin in step (d) but prior to step (e) said knee is flexed about 5 times. 
     
     
         38 . The method of any one of  claims 34 - 37 , wherein in step (e) fluid in the intra-articular space of the joint of said knee is maintained at a temperature in the range of from 26° C. to about 33° C. for a duration of at least 30 minutes. 
     
     
         39 . The method of any one of  claims 34 - 37 , wherein in step (e) fluid in the intra-articular space of the joint of said knee is maintained at a temperature in the range of from 26° C. to about 33° C. for a duration of from about 30 minutes to about 90 minutes. 
     
     
         40 . The method of any one of  claims 34 - 37 , wherein in step (e) fluid in the intra-articular space of the joint of said knee is maintained at a temperature in the range of from 26° C. to about 28° C. for a duration of at least 30 minutes. 
     
     
         41 . The method of any one of  claims 34 - 37 , wherein in step (e) fluid in the intra-articular space of the joint of said knee is maintained at a temperature in the range of from 26° C. to about 28° C. for a duration of from about 30 minutes to about 90 minutes. 
     
     
         42 . The method of any one of  claims 34 - 37 , wherein in step (e) fluid in the intra-articular space of the joint of said knee is maintained at a temperature in the range of from 28° C. to about 30° C. for a duration of at least 30 minutes. 
     
     
         43 . The method of any one of  claims 34 - 37 , wherein in step (e) fluid in the intra-articular space of the joint of said knee is maintained at a temperature in the range of from 28° C. to about 30° C. for a duration of from about 30 minutes to about 90 minutes. 
     
     
         44 . The method of any one of  claims 34 - 37 , wherein in step (e) fluid in the intra-articular space of the joint of said knee is maintained at a temperature in the range of from 30° C. to about 32° C. for a duration of at least 30 minutes. 
     
     
         45 . The method of any one of  claims 34 - 37 , wherein in step (e) fluid in the intra-articular space of the joint of said knee is maintained at a temperature in the range of from 30° C. to about 32° C. for a duration of from about 30 minutes to about 90 minutes. 
     
     
         46 . The method of any one of  claims 34 - 37 , wherein in step (e) fluid in the intra-articular space of the joint of said knee is maintained at a temperature of about 26° C. for a duration of at least 30 minutes. 
     
     
         47 . The method of any one of  claims 34 - 37 , wherein in step (e) fluid in the intra-articular space of the joint of said knee is maintained at a temperature of about 26° C. for a duration of from about 30 minutes to about 90 minutes. 
     
     
         48 . The method of any one of  claims 34 - 37 , wherein in step (e) fluid in the intra-articular space of the joint of said knee is maintained at a temperature of about 27° C. for a duration of at least 30 minutes. 
     
     
         49 . The method of any one of  claims 34 - 37 , wherein in step (e) fluid in the intra-articular space of the joint of said knee is maintained at a temperature of about 27° C. for a duration of from about 30 minutes to about 90 minutes. 
     
     
         50 . The method of any one of  claims 34 - 37 , wherein in step (e) fluid in the intra-articular space of the joint of said knee is maintained at a temperature of about 28° C. for a duration of at least 30 minutes. 
     
     
         51 . The method of any one of  claims 34 - 37 , wherein in step (e) fluid in the intra-articular space of the joint of said knee is maintained at a temperature of about 28° C. for a duration of from about 30 minutes to about 90 minutes. 
     
     
         52 . The method of any one of  claims 34 - 37 , wherein in step (e) fluid in the intra-articular space of the joint of said knee is maintained at a temperature of about 29° C. for a duration of at least 30 minutes. 
     
     
         53 . The method of any one of  claims 34 - 37 , wherein in step (e) fluid in the intra-articular space of the joint of said knee is maintained at a temperature of about 29° C. for a duration of from about 30 minutes to about 90 minutes. 
     
     
         54 . The method of any one of  claims 34 - 37 , wherein in step (e) fluid in the intra-articular space of the joint of said knee is maintained at a temperature of about 30° C. for a duration of at least 30 minutes. 
     
     
         55 . The method of any one of  claims 34 - 37 , wherein in step (e) fluid in the intra-articular space of the joint of said knee is maintained at a temperature of about 30° C. for a duration of from about 30 minutes to about 90 minutes. 
     
     
         56 . The method of any one of  claims 34 - 37 , wherein in step (e) fluid in the intra-articular space of the joint of said knee is maintained at a temperature of about 31° C. for a duration of at least 30 minutes. 
     
     
         57 . The method of any one of  claims 34 - 37 , wherein in step (e) fluid in the intra-articular space of the joint of said knee is maintained at a temperature of about 31° C. for a duration of from about 30 minutes to about 90 minutes. 
     
     
         58 . The method of any one of  claims 34 - 37 , wherein in step (e) fluid in the intra-articular space of the joint of said knee is maintained at a temperature of about 32° C. for a duration of at least 30 minutes. 
     
     
         59 . The method of any one of  claims 34 - 37 , wherein in step (e) fluid in the intra-articular space of the joint of said knee is maintained at a temperature of about 32° C. for a duration of from about 30 minutes to about 90 minutes. 
     
     
         60 . The method of any one of  claims 34 - 37 , wherein in step (e) fluid in the intra-articular space of the joint of said knee is maintained at a temperature of about 33° C. for a duration of at least 30 minutes. 
     
     
         61 . The method of any one of  claims 34 - 37 , wherein in step (e) fluid in the intra-articular space of the joint of said knee is maintained at a temperature of about 33° C. for a duration of from about 30 minutes to about 90 minutes. 
     
     
         62 . The method of any one of  claims 34 - 61 , wherein step (c) comprises applying a cooling article to an exterior surface of the knee to achieve a temperature in the range of from about 26° C. to about 28° C. for fluid in the intra-articular space of the joint of said knee. 
     
     
         63 . The method of any one of  claims 34 - 61 , wherein step (c) comprises applying a cooling article to an exterior surface of the knee to achieve a temperature in the range of from about 28° C. to about 30° C. for fluid in the intra-articular space of the joint of said knee. 
     
     
         64 . The method of any one of  claims 34 - 61 , wherein step (c) comprises applying a cooling article to an exterior surface of the knee to achieve a temperature in the range of from about 30° C. to about 32° C. for fluid in the intra-articular space of the joint of said knee. 
     
     
         65 . The method of any one of  claims 34 - 61 , wherein step (c) comprises applying a cooling article to an exterior surface of the knee to achieve a temperature of about 26° C. for fluid in the intra-articular space of the joint of said knee. 
     
     
         66 . The method of any one of  claims 34 - 61 , wherein step (c) comprises applying a cooling article to an exterior surface of the knee to achieve a temperature of about 27° C. for fluid in the intra-articular space of the joint of said knee. 
     
     
         67 . The method of any one of  claims 34 - 61 , wherein step (c) comprises applying a cooling article to an exterior surface of the knee to achieve a temperature of about 28° C. for fluid in the intra-articular space of the joint of said knee. 
     
     
         68 . The method of any one of  claims 34 - 61 , wherein step (c) comprises applying a cooling article to an exterior surface of the knee to achieve a temperature of about 29° C. for fluid in the intra-articular space of the joint of said knee. 
     
     
         69 . The method of any one of  claims 34 - 61 , wherein step (c) comprises applying a cooling article to an exterior surface of the knee to achieve a temperature of about 30° C. for fluid in the intra-articular space of the joint of said knee. 
     
     
         70 . The method of any one of  claims 34 - 61 , wherein step (c) comprises applying a cooling article to an exterior surface of the knee to achieve a temperature of about 31° C. for fluid in the intra-articular space of the joint of said knee. 
     
     
         71 . The method of any one of  claims 34 - 61 , wherein step (c) comprises applying a cooling article to an exterior surface of the knee to achieve a temperature of about 32° C. for fluid in the intra-articular space of the joint of said knee. 
     
     
         72 . The method of any one of  claims 34 - 61 , wherein step (c) comprises applying a cooling article to an exterior surface of the knee to achieve a temperature of about 33° C. for fluid in the intra-articular space of the joint of said knee. 
     
     
         73 . The method of any one of  claims 34 - 61 , wherein step (c) comprises applying a cooling article to an exterior surface of the knee to achieve a temperature in the range of from about 28° C. to about 30° C. for fluid in the intra-articular space of the joint of said knee. 
     
     
         74 . The method of any one of  claims 34 - 73 , wherein in step (a) the cooling article is applied for a duration of about 15 minutes to the exterior surface of the patient's knee presenting with osteoarthritic knee joint pain. 
     
     
         75 . The method of any one of  claims 34 - 74 , wherein in step (b) the dose of lidocaine is about 0.3 g. 
     
     
         76 . The method of any one of  claims 34 - 75 , wherein in step (b) the dose of lidocaine is 0.3 g. 
     
     
         77 . The method of any one of  claims 34 - 76 , wherein the pharmaceutical composition comprising a single pain-relief agent is an aqueous mixture containing lidocaine at a concentration of about 2% w/w. 
     
     
         78 . The method of any one of  claims 34 - 77 , wherein the pharmaceutical composition comprising a single pain-relief agent further comprises sodium chloride. 
     
     
         79 . The method of any one of  claims 34 - 77 , wherein the pharmaceutical composition comprising a single pain-relief agent further comprises sodium chloride at a concentration ranging from about 4 mg/mL to about 8 mg/mL. 
     
     
         80 . The method of any one of  claims 34 - 79 , wherein the pharmaceutical composition comprising a single pain-relief agent has a volume in the range of from about 13 mL to about 17 mL. 
     
     
         81 . The method of any one of  claims 34 - 79 , wherein the pharmaceutical composition comprising a single pain-relief agent has a volume of about 15 mL. 
     
     
         82 . The method of any one of  claims 34 - 81 , wherein the pharmaceutical composition comprising capsaicin is an aqueous mixture containing capsaicin. 
     
     
         83 . The method of any one of  claims 34 - 82 , wherein the pharmaceutical composition comprising capsaicin has a volume of about 4 mL. 
     
     
         84 . The method of any one of  claims 34 - 82 , wherein the pharmaceutical composition comprising capsaicin has a volume of about 2 mL. 
     
     
         85 . The method of any one of  claims 34 - 84 , wherein the cooling article has an exterior surface temperature in the range of from about 6° C. to about 13° C. for application to the exterior surface of said knee. 
     
     
         86 . The method of any one of  claims 34 - 84 , wherein the cooling article has an exterior surface temperature in the range of from about 7° C. to about 13° C. for application to the exterior surface of said knee. 
     
     
         87 . The method of any one of  claims 34 - 84 , wherein the cooling article has an exterior surface temperature in the range of from about 7° C. to about 10° C. for application to the exterior surface of said knee. 
     
     
         88 . The method of any one of  claims 34 - 84 , wherein the cooling article has an exterior surface temperature in the range of from about 5° C. to about 10° C. for application to the exterior surface of said knee. 
     
     
         89 . The method of any one of  claims 34 - 84 , wherein the cooling article has an exterior surface temperature in the range of from about 8° C. to about 10° C. for application to the exterior surface of said knee. 
     
     
         90 . The method of any one of  claims 34 - 84 , wherein the cooling article has an exterior surface temperature in the range of from about 6° C. to about 8° C. for application to the exterior surface of said knee. 
     
     
         91 . The method of any one of  claims 34 - 84 , wherein the cooling article has an exterior surface temperature in the range of from about 5° C. to about 8° C. for application to the exterior surface of said knee. 
     
     
         92 . The method of any one of  claims 34 - 84 , wherein the cooling article has an exterior surface temperature in the range of from about 5° C. to about 7° C. for application to the exterior surface of said knee. 
     
     
         93 . The method of any one of  claims 34 - 84 , wherein the cooling article has an exterior surface temperature of about 12° C. for application to the exterior surface of said knee. 
     
     
         94 . The method of any one of  claims 34 - 84 , wherein the cooling article has an exterior surface temperature of about 11° C. for application to the exterior surface of said knee. 
     
     
         95 . The method of any one of  claims 34 - 84 , wherein the cooling article has an exterior surface temperature of about 10° C. for application to the exterior surface of said knee. 
     
     
         96 . The method of any one of  claims 34 - 84 , wherein the cooling article has an exterior surface temperature of about 9° C. for application to the exterior surface of said knee. 
     
     
         97 . The method of any one of  claims 34 - 84 , wherein the cooling article has an exterior surface temperature of about 8° C. for application to the exterior surface of said knee. 
     
     
         98 . The method of any one of  claims 34 - 84 , wherein the cooling article has an exterior surface temperature of about 7° C. for application to the exterior surface of said knee. 
     
     
         99 . The method of any one of  claims 34 - 84 , wherein the cooling article has an exterior surface temperature of about 6° C. for application to the exterior surface of said knee. 
     
     
         100 . The method of any one of  claims 34 - 84 , wherein the cooling article has an exterior surface temperature of about 5° C. for application to the exterior surface of said knee. 
     
     
         101 . The method of any one of  claims 34 - 100 , wherein in step (a) the cooling article is applied for a duration of from about 5 minutes to about 20 minutes to the exterior surface of said knee. 
     
     
         102 . The method of any one of  claims 34 - 100 , wherein in step (a) the cooling article is applied for a duration of about 10 minutes to the exterior surface of said knee. 
     
     
         103 . The method of any one of  claims 34 - 102 , wherein in step (c) the cooling article is applied for a duration of from about 15 minutes to about 45 minutes to the exterior surface of said knee. 
     
     
         104 . The method of any one of  claims 34 - 102 , wherein in step (c) the cooling article is applied for a duration of about 30 minutes to the exterior surface of said knee. 
     
     
         105 . The method of any one of  claims 34 - 104 , wherein in step (e) the cooling article is applied for a duration of from about 15 minutes to about 90 minutes to the exterior surface of said knee. 
     
     
         106 . The method of any one of  claims 34 - 104 , wherein in step (e) the cooling article is applied for a duration of from about 30 minutes to about 90 minutes to the exterior surface of said knee. 
     
     
         107 . The method of any one of  claims 34 - 104 , wherein in step (e) the cooling article is applied for a duration of from about 30 minutes to about 60 minutes to the exterior surface of said knee. 
     
     
         108 . The method of any one of  claims 34 - 104 , wherein in step (e) the cooling article is applied for a duration of from about 60 minutes to about 90 minutes to the exterior surface of said knee. 
     
     
         109 . The method of any one of  claims 1 - 108 , wherein other than the procedures set forth in steps (a), (b), (c), (d), (e), and optionally flexing said knee, the method does not contain any procedure that reduces transient burning sensation experienced by the patient due to administration of capsaicin. 
     
     
         110 . The method of any one of  claims 1 - 109 , wherein other than the procedures set forth in steps (a), (b), (c), (d), (e), and optionally flexing said knee, the method does not contain any procedure that reduces osteoarthritic knee joint pain. 
     
     
         111 . The method of any one of  claims 1 - 108 , wherein other administration of (i) the pharmaceutical composition comprising lidocaine and (ii) the pharmaceutical composition comprising capsaicin, the patient does not receive any other pain-relief medicine. 
     
     
         112 . The method of any one of  claims 1 - 111 , wherein the patient experiences transient burning sensation no greater than level one on a visual analog scale ranging from zero to four, due to administering the pharmaceutical composition comprising capsaicin. 
     
     
         113 . The method of any one of  claims 1 - 111 , wherein the patient experiences transient burning sensation no greater than level two on a visual analog scale ranging from zero to four, due to administering the pharmaceutical composition comprising capsaicin. 
     
     
         114 . The method of  claim 112  or  113 , wherein transient burning sensation is evaluated at about 10 minutes after administration of the pharmaceutical composition comprising capsaicin. 
     
     
         115 . The method of  claim 112  or  113 , wherein transient burning sensation is evaluated at about 30 minutes after administration of the pharmaceutical composition comprising capsaicin. 
     
     
         116 . The method of  claim 112  or  113 , wherein transient burning sensation is evaluated at about 60 minutes after administration of the pharmaceutical composition comprising capsaicin. 
     
     
         117 . The method of any one of  claims 1 - 116 , wherein the method is characterized by achieving a reduction in osteoarthritic knee joint pain for a duration of at least 3 months. 
     
     
         118 . The method of any one of  claims 1 - 116 , wherein the method is characterized by achieving a reduction in osteoarthritic knee joint pain for a duration of at least 4 months. 
     
     
         119 . The method of any one of  claims 1 - 116 , wherein the method is characterized by achieving a reduction in osteoarthritic knee joint pain for a duration of at least 5 months. 
     
     
         120 . The method of any one of  claims 1 - 116 , wherein the method is characterized by achieving a reduction in osteoarthritic knee joint pain for a duration of at least 6 months. 
     
     
         121 . The method of any one of  claims 1 - 116 , wherein the method is characterized by achieving a reduction in osteoarthritic knee joint pain for a duration of at least 7 months. 
     
     
         122 . The method of any one of  claims 1 - 116  wherein the method is characterized by achieving a reduction in osteoarthritic knee joint pain for a duration of at least 8 months. 
     
     
         123 . The method of any one of  claims 1 - 116 , wherein the method is characterized by achieving a reduction in osteoarthritic knee joint pain for a duration of at least 9 months. 
     
     
         124 . The method of any one of  claims 1 - 116 , wherein the method is characterized by achieving a reduction in osteoarthritic knee joint pain for a duration of at least 10 months. 
     
     
         125 . The method of any one of  claims 1 - 116 , wherein the method is characterized by achieving a reduction in osteoarthritic knee joint pain for a duration of at least 11 months. 
     
     
         126 . The method of any one of  claims 1 - 116 , wherein the method is characterized by achieving a reduction in osteoarthritic knee joint pain for a duration of at least 12 months. 
     
     
         127 . The method of any one of  claims 1 - 116 , wherein the method is characterized by achieving a reduction in osteoarthritic knee joint pain for a duration of 4 months to 6 months. 
     
     
         128 . The method of any one of  claims 1 - 116 , wherein the method is characterized by achieving a reduction in osteoarthritic knee joint pain for a duration of 6 months to 9 months. 
     
     
         129 . The method of any one of  claims 1 - 116 , wherein the method is characterized by achieving a reduction in osteoarthritic knee joint pain for a duration of 6 months to 12 months. 
     
     
         130 . The method of any one of  claims 1 - 116 , wherein the method is characterized by achieving a reduction in osteoarthritic knee joint pain for a duration of 9 months to 12 months. 
     
     
         131 . The method of any one of  claims 1 - 130 , wherein the cooling article is a material wrap cooled via a circulating fluid. 
     
     
         132 . The method of any one of  claims 1 - 130 , wherein the cooling article is a textile wrap cooled via a circulating fluid. 
     
     
         133 . The method of any one of  claims 1 - 132 , wherein the cooling article covers at least 70% of the external surface of said patient's knee. 
     
     
         134 . The method of any one of  claims 1 - 132 , wherein the cooling article covers at least 80% of the external surface of said patient's knee. 
     
     
         135 . The method of any one of  claims 1 - 132 , wherein the cooling article covers at least 90% of the external surface of said patient's knee. 
     
     
         136 . The method of any one of  claims 1 - 132 , wherein the cooling article covers at least 95% of the external surface of said patient's knee. 
     
     
         137 . A method of ameliorating joint pain in a human patient, comprising:
 a. optionally applying a cooling article to a human patient's skin in proximity to a joint in need of pain relief therapy; then   b. optionally administering a local anesthetic agent into said joint; then   c. applying for a duration of at least about 10 minutes a cooling article to the patient's skin in proximity to said joint, wherein the cooling article has an exterior surface temperature in the range of from about 1° C. to about 15° C. for application to the human patient's skin in proximity to said joint; then   d. administering by injection into said joint a pharmaceutical composition comprising capsaicin in order to deliver a dose of capsaicin in an amount of from about 0.01 mg to about 4 mg; and then   e. optionally applying for a duration of at least about 10 minutes a cooling article to the patient's skin in proximity to said joint, wherein the cooling article has an exterior surface temperature in the range of from about 1° C. to about 15° C. for application to the human patient's skin in proximity to said joint;
 to thereby ameliorate joint pain in the human patient. 
   
     
     
         138 . A method of attenuating transient burning sensation due to injection of capsaicin into a joint in a human patient, comprising:
 a. optionally applying a cooling article to a human patient's skin in proximity to a joint in need of pain relief therapy;   b. optionally administering a local anesthetic agent into said joint;   c. applying for a duration of at least about 10 minutes a cooling article to the patient's skin in proximity to said joint, wherein the cooling article has an exterior surface temperature in the range of from about 1° C. to about 15° C. for application to the human patient's skin in proximity to said joint; then   d. administering by injection into said joint a pharmaceutical composition comprising capsaicin in order to deliver a dose of capsaicin in an amount of from about 0.01 mg to about 4 mg; and then   e. optionally applying for a duration of at least about 10 minutes a cooling article to the patient's skin in proximity to said joint, wherein the cooling article has an exterior surface temperature in the range of from about 1° C. to about 15° C. for application to the human patient's skin in proximity to said joint;
 to thereby attenuate transient burning sensation due to injection of capsaicin. 
   
     
     
         139 . A method of ameliorating joint pain in a human patient, comprising:
 a. optionally applying a cooling article to a human patient's skin in proximity to a joint in need of pain relief therapy; then   b. optionally administering a local anesthetic agent into said joint; then   c. applying a cooling article to the patient's skin in proximity to said joint to achieve a temperature in the range of from about 20° C. to about 33° C. for tissue or fluid in the interior of the joint; then   d. administering by injection into said joint a pharmaceutical composition comprising capsaicin in order to deliver a dose of capsaicin in an amount of from about 0.01 mg to about 4 mg; and then   e. optionally applying a cooling article to the patient's skin in proximity to said joint;
 to thereby ameliorate joint pain in the human patient. 
   
     
     
         140 . A method of attenuating transient burning sensation due to injection of capsaicin into a joint in a human patient, comprising:
 a. optionally applying a cooling article to a human patient's skin in proximity to a joint in need of pain relief therapy;   b. optionally administering a local anesthetic agent into said joint;   c. applying a cooling article to the patient's skin in proximity to said joint to achieve a temperature in the range of from about 20° C. to about 33° C. for tissue or fluid in the interior of the joint; then   d. administering by injection into said joint a pharmaceutical composition comprising capsaicin in order to deliver a dose of capsaicin in an amount of from about 0.01 mg to about 4 mg; and then   e. optionally applying a cooling article to the patient's skin in proximity to said joint;
 to thereby attenuate transient burning sensation due to injection of capsaicin. 
   
     
     
         141 . The method of  claim 139  or  140 , wherein step (c) comprises applying a cooling article to the patient's skin in proximity to the joint to achieve a temperature in the range of from about 20° C. to about 22° C. for tissue or fluid in the interior of the joint. 
     
     
         142 . The method of  claim 139  or  140 , wherein step (c) comprises applying a cooling article to the patient's skin in proximity to the joint to achieve a temperature in the range of from about 22° C. to about 24° C. for tissue or fluid in the interior of the joint. 
     
     
         143 . The method of  claim 139  or  140 , wherein step (c) comprises applying a cooling article to the patient's skin in proximity to the joint to achieve a temperature in the range of from about 24° C. to about 26° C. for tissue or fluid in the interior of the joint. 
     
     
         144 . The method of  claim 139  or  140 , wherein step (c) comprises applying a cooling article to the patient's skin in proximity to the joint to achieve a temperature in the range of from about 26° C. to about 28° C. for tissue or fluid in the interior of the joint. 
     
     
         145 . The method of  claim 139  or  140 , wherein step (c) comprises applying a cooling article to the patient's skin in proximity to the joint to achieve a temperature in the range of from about 28° C. to about 30° C. for tissue or fluid in the interior of the joint. 
     
     
         146 . The method of  claim 139  or  140 , wherein step (c) comprises applying a cooling article to the patient's skin in proximity to the joint to achieve a temperature in the range of from about 30° C. to about 32° C. for tissue or fluid in the interior of the joint. 
     
     
         147 . The method of  claim 139  or  140 , wherein step (c) comprises applying a cooling article to the patient's skin in proximity to the joint to achieve a temperature of about 20° C. for tissue or fluid in the interior of the joint. 
     
     
         148 . The method of  claim 139  or  140 , wherein step (c) comprises applying a cooling article to the patient's skin in proximity to the joint to achieve a temperature of about 21° C. for tissue or fluid in the interior of the joint. 
     
     
         149 . The method of  claim 139  or  140 , wherein step (c) comprises applying a cooling article to the patient's skin in proximity to the joint to achieve a temperature of about 22° C. for tissue or fluid in the interior of the joint. 
     
     
         150 . The method of  claim 139  or  140 , wherein step (c) comprises applying a cooling article to the patient's skin in proximity to the joint to achieve a temperature of about 23° C. for tissue or fluid in the interior of the joint. 
     
     
         151 . The method of  claim 139  or  140 , wherein step (c) comprises applying a cooling article to the patient's skin in proximity to the joint to achieve a temperature of about 24° C. for tissue or fluid in the interior of the joint. 
     
     
         152 . The method of  claim 139  or  140 , wherein step (c) comprises applying a cooling article to the patient's skin in proximity to the joint to achieve a temperature of about 25° C. for tissue or fluid in the interior of the joint. 
     
     
         153 . The method of  claim 139  or  140 , wherein step (c) comprises applying a cooling article to the patient's skin in proximity to the joint to achieve a temperature of about 26° C. for tissue or fluid in the interior of the joint. 
     
     
         154 . The method of  claim 139  or  140 , wherein step (c) comprises applying a cooling article to the patient's skin in proximity to the joint to achieve a temperature of about 27° C. for tissue or fluid in the interior of the joint. 
     
     
         155 . The method of  claim 139  or  140 , wherein step (c) comprises applying a cooling article to the patient's skin in proximity to the joint to achieve a temperature of about 28° C. for tissue or fluid in the interior of the joint. 
     
     
         156 . The method of  claim 139  or  140 , wherein step (c) comprises applying a cooling article to the patient's skin in proximity to the joint to achieve a temperature of about 29° C. for tissue or fluid in the interior of the joint. 
     
     
         157 . The method of  claim 139  or  140 , wherein step (c) comprises applying a cooling article to the patient's skin in proximity to the joint to achieve a temperature of about 30° C. for tissue or fluid in the interior of the joint. 
     
     
         158 . The method of  claim 139  or  140 , wherein step (c) comprises applying a cooling article to the patient's skin in proximity to the joint to achieve a temperature of about 31° C. for tissue or fluid in the interior of the joint. 
     
     
         159 . The method of  claim 139  or  140 , wherein step (c) comprises applying a cooling article to the patient's skin in proximity to the joint to achieve a temperature of about 32° C. for tissue or fluid in the interior of the joint. 
     
     
         160 . The method of  claim 139  or  140 , wherein step (c) comprises applying a cooling article to the patient's skin in proximity to the joint to achieve a temperature of about 33° C. for tissue or fluid in the interior of the joint. 
     
     
         161 . The method of any one of  claims 137 - 160 , wherein the method comprises step (e) in which a cooling article is applied for a duration of at least about 10 minutes to the patient's skin in proximity to said joint, wherein the cooling article has an exterior surface temperature in the range of from about 1° C. to about 15° C. for application to the exterior surface of the human patient's skin in proximity to said joint. 
     
     
         162 . The method of any one of  claims 137 - 160 , wherein the method comprises step (e) in which a cooling article is applied to the patient's skin in proximity to the joint to achieve a temperature in the range of from about 20° C. to about 22° C. for tissue or fluid in the interior of the joint for a duration of at least 15 minutes. 
     
     
         163 . The method of any one of  claims 137 - 160 , wherein the method comprises step (e) in which a cooling article is applied to the patient's skin in proximity to the joint to achieve a temperature in the range of from about 22° C. to about 24° C. for tissue or fluid in the interior of the joint for a duration of at least 15 minutes. 
     
     
         164 . The method of any one of  claims 137 - 160 , wherein the method comprises step (e) in which a cooling article is applied to the patient's skin in proximity to the joint to achieve a temperature in the range of from about 24° C. to about 26° C. for tissue or fluid in the interior of the joint for a duration of at least 15 minutes. 
     
     
         165 . The method of any one of  claims 137 - 160 , wherein the method comprises step (e) in which a cooling article is applied to the patient's skin in proximity to the joint to achieve a temperature in the range of from about 26° C. to about 28° C. for tissue or fluid in the interior of the joint for a duration of at least 15 minutes. 
     
     
         166 . The method of any one of  claims 137 - 160 , wherein the method comprises step (e) in which a cooling article is applied to the patient's skin in proximity to the joint to achieve a temperature in the range of from about 28° C. to about 30° C. for tissue or fluid in the interior of the joint for a duration of at least 15 minutes. 
     
     
         167 . The method of any one of  claims 137 - 160 , wherein the method comprises step (e) in which a cooling article is applied to the patient's skin in proximity to the joint to achieve a temperature in the range of from about 30° C. to about 32° C. for tissue or fluid in the interior of the joint for a duration of at least 15 minutes. 
     
     
         168 . The method of any one of  claims 162 - 167 , wherein said duration in step (e) is at least 30 minutes. 
     
     
         169 . The method of any one of  claims 162 - 167 , wherein said duration in step (e) is from about 30 minutes to about 90 minutes. 
     
     
         170 . The method of any one of  claims 162 - 167 , wherein said duration in step (e) is from about 30 minutes to about 60 minutes. 
     
     
         171 . The method of any one of  claims 162 - 167 , wherein said duration in step (e) is from about 60 minutes to about 90 minutes. 
     
     
         172 . The method of any one of  claims 137 - 171 , wherein the method comprises step (a) in which a cooling article is applied to a human patient's skin in proximity to a joint in need of pain relief therapy 
     
     
         173 . The method of any one of  claims 137 - 171 , wherein the method comprises step (a) in which for a duration of from about 5 minutes to about 30 minutes a cooling article is applied to a human patient's skin in proximity to a joint in need of pain relief therapy. 
     
     
         174 . The method of any one of  claims 137 - 173 , wherein the method comprises step (b) of administering a local anesthetic agent into said joint. 
     
     
         175 . The method of  claim 174 , wherein the local anesthetic agent is a caine analagesic. 
     
     
         176 . The method of  claim 174  wherein the local anesthetic agent is lidocaine or a pharmaceutically acceptable salt thereof. 
     
     
         177 . The method of  claim 174 , wherein the local anesthetic agent is lidocaine hydrochloride. 
     
     
         178 . The method of any one of  claims 137 - 173 , wherein the method comprises step (b) of administering by injection into the joint a pharmaceutical composition comprising lidocaine in order to deliver a dose of lidocaine in an amount of about 0.1 g to about 0.5 g; 
     
     
         179 . The method of  claim 178 , wherein the dose of lidocaine is about 0.3 g. 
     
     
         180 . The method of  claim 178  or  179 , wherein the pharmaceutical composition comprising lidocaine is an aqueous mixture containing lidocaine at a concentration of about 2% w/w. 
     
     
         181 . The method of any one of  claims 137 - 180 , wherein after administration of the pharmaceutical composition comprising capsaicin in step (d) but prior to step (e) said joint is flexed. 
     
     
         182 . The method of any one of  claims 137 - 180 , wherein after administration of the pharmaceutical composition comprising capsaicin in step (d) but prior to step (e) said joint is flexed about 5 times. 
     
     
         183 . The method of any one of  claims 137 - 182 , wherein the pharmaceutical composition comprising capsaicin is an aqueous mixture containing capsaicin. 
     
     
         184 . The method of any one of  claims 137 - 183 , wherein the joint pain is arthritic joint pain. 
     
     
         185 . The method of any one of  claims 137 - 183 , wherein the joint pain is osteoarthritic joint pain. 
     
     
         186 . The method of any one of  claims 137 - 185 , wherein the joint is a knee joint, hip joint, shoulder joint, elbow joint, ankle joint, carpal joint, tarsal joint, or metatarsal joint. 
     
     
         187 . The method of any one of  claims 137 - 185 , wherein the joint is a knee joint. 
     
     
         188 . The method of any one of  claims 137 - 185 , wherein the joint is a thumb joint. 
     
     
         189 . The method of any one of  claims 137 - 188 , wherein the pharmaceutical composition comprising capsaicin has a volume of about 4 mL. 
     
     
         190 . The method of any one of  claims 137 - 188 , wherein the pharmaceutical composition comprising capsaicin has a volume of about 2 mL. 
     
     
         191 . The method of any one of  claims 137 - 188 , wherein the pharmaceutical composition comprising capsaicin has a volume of about 1 mL. 
     
     
         192 . The method of any one of  claims 137 - 188 , wherein the pharmaceutical composition comprising capsaicin has a volume of about 0.5 mL. 
     
     
         193 . The method of any one of  claims 137 - 192 , wherein the cooling article has an exterior surface temperature in the range of from about 1° C. to about 3° C. for application to the human patient's skin in proximity to said joint. 
     
     
         194 . The method of any one of  claims 137 - 192 , wherein the cooling article has an exterior surface temperature in the range of from about 3° C. to about 5° C. for application to the human patient's skin in proximity to said joint. 
     
     
         195 . The method of any one of  claims 137 - 192 , wherein the cooling article has an exterior surface temperature in the range of from about 5° C. to about 7° C. for application to the human patient's skin in proximity to said joint. 
     
     
         196 . The method of any one of  claims 137 - 192 , wherein the cooling article has an exterior surface temperature in the range of from about 7° C. to about 9° C. for application to the human patient's skin in proximity to said joint. 
     
     
         197 . The method of any one of  claims 137 - 192 , wherein the cooling article has an exterior surface temperature in the range of from about 9° C. to about 11° C. for application to the human patient's skin in proximity to said joint. 
     
     
         198 . The method of any one of  claims 137 - 192 , wherein the cooling article has an exterior surface temperature in the range of from about 11° C. to about 13° C. for application to the human patient's skin in proximity to said joint. 
     
     
         199 . The method of any one of  claims 137 - 192 , wherein the cooling article has an exterior surface temperature in the range of from about 13° C. to about 15° C. for application to the human patient's skin in proximity to said joint. 
     
     
         200 . The method of any one of  claims 137 - 192 , wherein the cooling article has an exterior surface temperature of about 1° C. for application to the human patient's skin in proximity to said joint. 
     
     
         201 . The method of any one of  claims 137 - 192 , wherein the cooling article has an exterior surface temperature of about 2° C. for application to the human patient's skin in proximity to said joint. 
     
     
         202 . The method of any one of  claims 137 - 192 , wherein the cooling article has an exterior surface temperature of about 3° C. for application to the human patient's skin in proximity to said joint. 
     
     
         203 . The method of any one of  claims 137 - 192 , wherein the cooling article has an exterior surface temperature of about 4° C. for application to the human patient's skin in proximity to said joint. 
     
     
         204 . The method of any one of  claims 137 - 192 , wherein the cooling article has an exterior surface temperature of about 5° C. for application to the human patient's skin in proximity to said joint. 
     
     
         205 . The method of any one of  claims 137 - 192 , wherein the cooling article has an exterior surface temperature of about 6° C. for application to the human patient's skin in proximity to said joint. 
     
     
         206 . The method of any one of  claims 137 - 192 , wherein the cooling article has an exterior surface temperature of about 7° C. for application to the human patient's skin in proximity to said joint. 
     
     
         207 . The method of any one of  claims 137 - 192 , wherein the cooling article has an exterior surface temperature of about 8° C. for application to the human patient's skin in proximity to said joint. 
     
     
         208 . The method of any one of  claims 137 - 192 , wherein the cooling article has an exterior surface temperature of about 9° C. for application to the human patient's skin in proximity to said joint. 
     
     
         209 . The method of any one of  claims 137 - 192 , wherein the cooling article has an exterior surface temperature of about 10° C. for application to the human patient's skin in proximity to said joint. 
     
     
         210 . The method of any one of  claims 137 - 192 , wherein the cooling article has an exterior surface temperature of about 11° C. for application to the human patient's skin in proximity to said joint. 
     
     
         211 . The method of any one of  claims 137 - 192 , wherein the cooling article has an exterior surface temperature of about 12° C. for application to the human patient's skin in proximity to said joint. 
     
     
         212 . The method of any one of  claims 137 - 192 , wherein the cooling article has an exterior surface temperature of about 13° C. for application to the human patient's skin in proximity to said joint. 
     
     
         213 . The method of any one of  claims 137 - 192 , wherein the cooling article has an exterior surface temperature of about 14° C. for application to the human patient's skin in proximity to said joint. 
     
     
         214 . The method of any one of  claims 137 - 192 , wherein the cooling article has an exterior surface temperature of about 15° C. for application to the human patient's skin in proximity to said joint. 
     
     
         215 . The method of any one of  claims 137 - 214 , wherein the dose of capsaicin is from about 0.01 mg to about 0.1 mg. 
     
     
         216 . The method of any one of  claims 137 - 214 , wherein the dose of capsaicin is from about 0.1 mg to about 0.5 mg. 
     
     
         217 . The method of any one of  claims 137 - 214 , wherein the dose of capsaicin is from about 0.5 mg to about 1.0 mg. 
     
     
         218 . The method of any one of  claims 137 - 214 , wherein the dose of capsaicin is from about 1 mg to about 1.5 mg. 
     
     
         219 . The method of any one of  claims 137 - 214 , wherein the dose of capsaicin is from about 1.5 mg to about 2.0 mg. 
     
     
         220 . The method of any one of  claims 137 - 214 , wherein the dose of capsaicin is from about 2.0 mg to about 4.0 mg. 
     
     
         221 . The method of any one of  claims 137 - 214 , wherein the dose of capsaicin is about 1 mg. 
     
     
         222 . The method of any one of  claims 137 - 214 , wherein the dose of capsaicin is 1 mg. 
     
     
         223 . The method of any one of  claims 137 - 222 , wherein other than the procedures set forth in steps (a), (b), (c), (d), (e), and optionally flexing said joint, the method does not contain any procedure that reduces transient burning sensation experienced by the patient due to administration of capsaicin. 
     
     
         224 . The method of any one of  claims 137 - 223 , wherein other than the procedures set forth in steps (a), (b), (c), (d), (e), and optionally flexing said joint, the method does not contain any procedure that reduces joint pain. 
     
     
         225 . The method of any one of  claims 137 - 223 , wherein other than administration of (i) the local anesthetic agent and (ii) the pharmaceutical composition comprising capsaicin, the patient does not receive any other pain-relief medicine. 
     
     
         226 . A method of ameliorating joint pain in a human patient, comprising:
 a. optionally applying a cooling article to a human patient's skin in proximity to a joint in need of pain relief therapy; then   b. optionally administering a local anesthetic agent into said joint; then   c. applying for a duration of at least about 10 minutes a cooling article to the patient's skin in proximity to said joint, wherein the cooling article has an exterior surface temperature in the range of from about 1° C. to about 15° C. for application to the human patient's skin in proximity to said joint; then   d. administering by injection into said joint a pharmaceutical composition comprising capsaicin in order to deliver a dose of capsaicin in an amount of about 1 mg; and then   e. optionally applying for a duration of at least about 10 minutes a cooling article to the patient's skin in proximity to said joint, wherein the cooling article has an exterior surface temperature in the range of from about 1° C. to about 15° C. for application to the human patient's skin in proximity to said joint;
 to thereby ameliorate joint pain in the human patient, wherein the joint pain is osteoarthritic joint pain, and the joint is a knee joint. 
   
     
     
         227 . A method of attenuating transient burning sensation due to injection of capsaicin into a joint in a human patient, comprising:
 a. optionally applying a cooling article to a human patient's skin in proximity to a joint in need of pain relief therapy;   b. optionally administering a local anesthetic agent into said joint;   c. applying for a duration of at least about 10 minutes a cooling article to the patient's skin in proximity to said joint, wherein the cooling article has an exterior surface temperature in the range of from about 1° C. to about 15° C. for application to the human patient's skin in proximity to said joint; then   d. administering by injection into said joint a pharmaceutical composition comprising capsaicin in order to deliver a dose of capsaicin in an amount of about 1 mg; and then   e. optionally applying for a duration of at least about 10 minutes a cooling article to the patient's skin in proximity to said joint, wherein the cooling article has an exterior surface temperature in the range of from about 1° C. to about 15° C. for application to the human patient's skin in proximity to said joint;
 to thereby attenuate transient burning sensation due to injection of capsaicin, wherein the joint pain is osteoarthritic joint pain, and the joint is a knee joint. 
   
     
     
         228 . A method of ameliorating joint pain in a human patient, comprising:
 a. optionally applying a cooling article to a human patient's skin in proximity to a joint in need of pain relief therapy; then   b. optionally administering a local anesthetic agent into said joint; then   c. applying a cooling article to the patient's skin in proximity to said joint to achieve a temperature in the range of from about 20° C. to about 33° C. for tissue or fluid in the interior of the joint; then   d. administering by injection into said joint a pharmaceutical composition comprising capsaicin in order to deliver a dose of capsaicin in an amount of about 1 mg; and then   e. optionally applying a cooling article to the patient's skin in proximity to said joint;
 to thereby ameliorate joint pain in the human patient, wherein the joint pain is osteoarthritic joint pain, and the joint is a knee joint. 
   
     
     
         229 . A method of attenuating transient burning sensation due to injection of capsaicin into a joint in a human patient, comprising:
 a. optionally applying a cooling article to a human patient's skin in proximity to a joint in need of pain relief therapy;   b. optionally administering a local anesthetic agent into said joint;   c. applying a cooling article to the patient's skin in proximity to said joint to achieve a temperature in the range of from about 20° C. to about 33° C. for tissue or fluid in the interior of the joint; then   d. administering by injection into said joint a pharmaceutical composition comprising capsaicin in order to deliver a dose of capsaicin in an amount of about 1 mg; and then   e. optionally applying a cooling article to the patient's skin in proximity to said joint;
 to thereby attenuate transient burning sensation due to injection of capsaicin, wherein the joint pain is osteoarthritic joint pain, and the joint is a knee joint. 
   
     
     
         230 . The method of  claim 228  or  229 , wherein step (c) comprises applying a cooling article to the patient's skin in proximity to the joint to achieve a temperature in the range of from about 24° C. to about 26° C. for tissue or fluid in the interior of the joint. 
     
     
         231 . The method of  claim 228  or  229 , wherein step (c) comprises applying a cooling article to the patient's skin in proximity to the joint to achieve a temperature in the range of from about 26° C. to about 28° C. for tissue or fluid in the interior of the joint. 
     
     
         232 . The method of  claim 228  or  229 , wherein step (c) comprises applying a cooling article to the patient's skin in proximity to the joint to achieve a temperature in the range of from about 28° C. to about 30° C. for tissue or fluid in the interior of the joint. 
     
     
         233 . The method of  claim 228  or  229 , wherein step (c) comprises applying a cooling article to the patient's skin in proximity to the joint to achieve a temperature in the range of from about 30° C. to about 32° C. for tissue or fluid in the interior of the joint. 
     
     
         234 . The method of  claim 228  or  229 , wherein step (c) comprises applying a cooling article to the patient's skin in proximity to the joint to achieve a temperature of about 27° C. for tissue or fluid in the interior of the joint. 
     
     
         235 . The method of  claim 228  or  229 , wherein step (c) comprises applying a cooling article to the patient's skin in proximity to the joint to achieve a temperature of about 28° C. for tissue or fluid in the interior of the joint. 
     
     
         236 . The method of  claim 228  or  229 , wherein step (c) comprises applying a cooling article to the patient's skin in proximity to the joint to achieve a temperature of about 29° C. for tissue or fluid in the interior of the joint. 
     
     
         237 . The method of  claim 228  or  229 , wherein step (c) comprises applying a cooling article to the patient's skin in proximity to the joint to achieve a temperature of about 30° C. for tissue or fluid in the interior of the joint. 
     
     
         238 . The method of  claim 228  or  229 , wherein step (c) comprises applying a cooling article to the patient's skin in proximity to the joint to achieve a temperature of about 31° C. for tissue or fluid in the interior of the joint. 
     
     
         239 . The method of  claim 228  or  229 , wherein step (c) comprises applying a cooling article to the patient's skin in proximity to the joint to achieve a temperature of about 32° C. for tissue or fluid in the interior of the joint. 
     
     
         240 . The method of any one of  claims 226 - 239 , wherein the method comprises step (e) in which a cooling article is applied for a duration of at least about 10 minutes to the patient's skin in proximity to said joint, wherein the cooling article has an exterior surface temperature in the range of from about 1° C. to about 15° C. for application to the exterior surface of the human patient's skin in proximity to said joint. 
     
     
         241 . The method of any one of  claims 226 - 240 , wherein the method comprises step (e) in which a cooling article is applied to the patient's skin in proximity to the joint to achieve a temperature in the range of from about 24° C. to about 26° C. for tissue or fluid in the interior of the joint for a duration of at least 15 minutes. 
     
     
         242 . The method of any one of  claims 226 - 240 , wherein the method comprises step (e) in which a cooling article is applied to the patient's skin in proximity to the joint to achieve a temperature in the range of from about 26° C. to about 28° C. for tissue or fluid in the interior of the joint for a duration of at least 15 minutes. 
     
     
         243 . The method of any one of  claims 226 - 240 , wherein the method comprises step (e) in which a cooling article is applied to the patient's skin in proximity to the joint to achieve a temperature in the range of from about 28° C. to about 30° C. for tissue or fluid in the interior of the joint for a duration of at least 15 minutes. 
     
     
         244 . The method of any one of  claims 226 - 240 , wherein the method comprises step (e) in which a cooling article is applied to the patient's skin in proximity to the joint to achieve a temperature in the range of from about 30° C. to about 32° C. for tissue or fluid in the interior of the joint for a duration of at least 15 minutes. 
     
     
         245 . The method of any one of  claims 240 - 244 , wherein said duration in step (e) is at least 20 minutes. 
     
     
         246 . The method of any one of  claims 240 - 244 , wherein said duration in step (e) is at least 30 minutes. 
     
     
         247 . The method of any one of  claims 240 - 244 , wherein said duration is step (e) from about 30 minutes to about 90 minutes. 
     
     
         248 . The method of any one of  claims 240 - 244 , wherein said duration is step (e) from about 30 minutes to about 60 minutes. 
     
     
         249 . The method of any one of  claims 226 - 248 , wherein the method comprises step (a) in which for a duration of from about 5 minutes to about 30 minutes a cooling article is applied to a human patient's skin in proximity to a joint in need of pain relief therapy. 
     
     
         250 . The method of any one of  claims 226 - 248 , wherein the method comprises step (a) in which for a duration of about 15 minutes a cooling article is applied to a human patient's skin in proximity to a joint in need of pain relief therapy. 
     
     
         251 . The method of any one of  claims 226 - 248 , wherein the method does not contain step (a). 
     
     
         252 . The method of any one of  claims 226 - 251 , wherein the method comprises step (b) of administering by injection into the joint a pharmaceutical composition comprising lidocaine in order to deliver a dose of lidocaine in an amount of about 0.1 g to about 0.5 g. 
     
     
         253 . The method of any one of  claims 226 - 251 , wherein the method comprises step (b) of administering by injection into the joint a pharmaceutical composition comprising a single pain-relief agent selected from the group consisting of lidocaine and a pharmaceutically acceptable salt thereof, in order to deliver a dose of lidocaine in an amount ranging from about 0.1 g to about 0.5 g. 
     
     
         254 . The method of any one of  claims 226 - 251 , wherein the method comprises the following additional step that is performed between steps (c) and (d): administering into said joint a pharmaceutical composition comprising a single pain-relief agent selected from the group consisting of lidocaine and a pharmaceutically acceptable salt thereof, in order to deliver a dose of lidocaine in an amount ranging from about 0.1 g to about 0.5 g. 
     
     
         255 . The method of  claim 254 , wherein the method does not contain step (b). 
     
     
         256 . The method of any one of  claims 252 - 255 , wherein the dose of lidocaine is about 0.3 g. 
     
     
         257 . The method of any one of  claims 252 - 255 , wherein the dose of lidocaine is about 0.15 g. 
     
     
         258 . The method of any one of  claims 252 - 256 , wherein the pharmaceutical composition comprising lidocaine is an aqueous mixture containing lidocaine at a concentration of about 2% w/w. 
     
     
         259 . The method of any one of  claim 252 - 255  or  257 , wherein the pharmaceutical composition comprising lidocaine is an aqueous mixture containing lidocaine at a concentration of about 1% w/w. 
     
     
         260 . The method of any one of  claims 252 - 259 , wherein the pharmaceutical composition comprising lidocaine has a volume in the range of from about 13 mL to about 17 mL. 
     
     
         261 . The method of any one of  claims 252 - 259 , wherein the pharmaceutical composition comprising lidocaine has a volume of about 15 mL. 
     
     
         262 . The method of any one of  claims 226 - 261 , wherein step (c) comprises applying for a duration of about 20 minutes the cooling article to an exterior surface of said knee. 
     
     
         263 . The method of any one of  claims 226 - 261 , wherein step (c) comprises applying for a duration of about 30 minutes the cooling article to an exterior surface of said knee. 
     
     
         264 . The method of any one of  claims 226 - 263 , wherein after administration of the pharmaceutical composition comprising capsaicin in step (d) but prior to step (e) said joint is flexed. 
     
     
         265 . The method of any one of  claims 226 - 263 , wherein after administration of the pharmaceutical composition comprising capsaicin in step (d) but prior to step (e) said joint is flexed about 5 times. 
     
     
         266 . The method of any one of  claims 226 - 265 , wherein the pharmaceutical composition comprising capsaicin is an aqueous mixture containing capsaicin. 
     
     
         267 . The method of any one of  claims 226 - 266 , wherein the pharmaceutical composition comprising capsaicin has a volume of about 2 mL. 
     
     
         268 . The method of any one of  claims 226 - 266 , wherein the pharmaceutical composition comprising capsaicin has a volume of about 1 mL. 
     
     
         269 . The method of any one of  claims 226 - 268 , wherein the cooling article has an exterior surface temperature in the range of from about 5° C. to about 15° C. for application to the human patient's skin in proximity to said joint. 
     
     
         270 . The method of any one of  claims 226 - 268 , wherein the cooling article has an exterior surface temperature in the range of from about 7° C. to about 13° C. for application to the human patient's skin in proximity to said joint. 
     
     
         271 . The method of any one of  claims 226 - 268 , wherein the cooling article has an exterior surface temperature in the range of from about 8° C. to about 10° C. for application to the human patient's skin in proximity to said joint. 
     
     
         272 . The method of any one of  claims 226 - 268 , wherein the cooling article has an exterior surface temperature in the range of from about 5° C. to about 7° C. for application to the human patient's skin in proximity to said joint. 
     
     
         273 . The method of any one of  claims 226 - 268 , wherein the cooling article has an exterior surface temperature in the range of from about 7° C. to about 9° C. for application to the human patient's skin in proximity to said joint. 
     
     
         274 . The method of any one of  claims 226 - 268 , wherein the cooling article has an exterior surface temperature in the range of from about 9° C. to about 11° C. for application to the human patient's skin in proximity to said joint. 
     
     
         275 . The method of any one of  claims 226 - 268 , wherein the cooling article has an exterior surface temperature in the range of from about 11° C. to about 13° C. for application to the human patient's skin in proximity to said joint. 
     
     
         276 . The method of any one of  claims 226 - 268 , wherein the cooling article has an exterior surface temperature in the range of from about 13° C. to about 15° C. for application to the human patient's skin in proximity to said joint. 
     
     
         277 . The method of any one of  claims 226 - 268 , wherein the cooling article has an exterior surface temperature of about 8° C. for application to the human patient's skin in proximity to said joint. 
     
     
         278 . The method of any one of  claims 226 - 268 , wherein the cooling article has an exterior surface temperature of about 9° C. for application to the human patient's skin in proximity to said joint. 
     
     
         279 . The method of any one of  claims 226 - 268 , wherein the cooling article has an exterior surface temperature of about 10° C. for application to the human patient's skin in proximity to said joint. 
     
     
         280 . The method of any one of  claims 226 - 268 , wherein the cooling article has an exterior surface temperature of about 11° C. for application to the human patient's skin in proximity to said joint. 
     
     
         281 . The method of any one of  claims 226 - 268 , wherein the cooling article has an exterior surface temperature of about 12° C. for application to the human patient's skin in proximity to said joint. 
     
     
         282 . The method of any one of  claims 226 - 281 , wherein other than administration of (i) the local anesthetic agent and (ii) the pharmaceutical composition comprising capsaicin, the patient does not receive any other pain-relief medicine. 
     
     
         283 . The method of any one of  claims 137 - 282 , wherein the patient experiences transient burning sensation no greater than level one on a visual analog scale ranging from zero to four, due to administering the pharmaceutical composition comprising capsaicin. 
     
     
         284 . The method of any one of  claims 137 - 282 , wherein the patient experiences transient burning sensation no greater than level two on a visual analog scale ranging from zero to four, due to administering the pharmaceutical composition comprising capsaicin. 
     
     
         285 . The method of  claim 283  or  284 , wherein transient burning sensation is evaluated at about 10 minutes after administration of the pharmaceutical composition comprising capsaicin. 
     
     
         286 . The method of  claim 283  or  284 , wherein transient burning sensation is evaluated at about 30 minutes after administration of the pharmaceutical composition comprising capsaicin. 
     
     
         287 . The method of  claim 283  or  284 , wherein transient burning sensation is evaluated at about 60 minutes after administration of the pharmaceutical composition comprising capsaicin. 
     
     
         288 . The method of any one of  claims 137 - 287 , wherein the method is characterized by achieving a reduction in joint pain for a duration of at least 3 months. 
     
     
         289 . The method of any one of  claims 137 - 287 , wherein the method is characterized by achieving a reduction in joint pain for a duration of at least 4 months. 
     
     
         290 . The method of any one of  claims 137 - 287 , wherein the method is characterized by achieving a reduction in joint pain for a duration of at least 5 months. 
     
     
         291 . The method of any one of  claims 137 - 287 , wherein the method is characterized by achieving a reduction in joint pain for a duration of at least 6 months. 
     
     
         292 . The method of any one of  claims 137 - 287 , wherein the method is characterized by achieving a reduction in joint pain for a duration of at least 7 months. 
     
     
         293 . The method of any one of  claims 137 - 287 , wherein the method is characterized by achieving a reduction in joint pain for a duration of at least 8 months. 
     
     
         294 . The method of any one of  claims 137 - 287 , wherein the method is characterized by achieving a reduction in joint pain for a duration of at least 9 months. 
     
     
         295 . The method of any one of  claims 137 - 287 , wherein the method is characterized by achieving a reduction in joint pain for a duration of at least 10 months. 
     
     
         296 . The method of any one of  claims 137 - 287 , wherein the method is characterized by achieving a reduction in joint pain for a duration of at least 11 months. 
     
     
         297 . The method of any one of  claims 137 - 287 , wherein the method is characterized by achieving a reduction in joint pain for a duration of at least 12 months. 
     
     
         298 . The method of any one of  claims 137 - 287 , wherein the method is characterized by achieving a reduction in joint pain for a duration of 4 months to 6 months. 
     
     
         299 . The method of any one of  claims 137 - 287 , wherein the method is characterized by achieving a reduction in joint pain for a duration of 6 months to 9 months. 
     
     
         300 . The method of any one of  claims 137 - 287 , wherein the method is characterized by achieving a reduction in joint pain for a duration of 6 months to 12 months. 
     
     
         301 . The method of any one of  claims 137 - 287 , wherein the method is characterized by achieving a reduction in joint pain for a duration of 9 months to 12 months. 
     
     
         302 . The method of any one of  claims 137 - 301 , wherein the cooling article is a material wrap cooled via a circulating fluid. 
     
     
         303 . The method of any one of  claims 137 - 301 , wherein the cooling article is a textile wrap cooled via a circulating fluid. 
     
     
         304 . The method of any one of  claims 137 - 301 , wherein the cooling article is an at least partially frozen gel pack. 
     
     
         305 . The method of any one of  claims 137 - 304 , wherein the cooling article covers at least 70% of the external surface of said joint. 
     
     
         306 . The method of any one of  claims 137 - 304 , wherein the cooling article covers at least 80% of the external surface of said joint. 
     
     
         307 . The method of any one of  claims 137 - 304 , wherein the cooling article covers at least 90% of the external surface of said joint. 
     
     
         308 . The method of any one of  claims 137 - 304 , wherein the cooling article covers at least 95% of the external surface of said joint. 
     
     
         309 . The method of any one of  claims 1 - 308 , wherein the capsaicin is a mixture of cis-capsaicin and trans-capsaicin that contains at least 98% by weight trans-capsaicin. 
     
     
         310 . The method of any one of  claims 1 - 308 , wherein the capsaicin is a mixture of cis-capsaicin and trans-capsaicin that contains at least 99% by weight trans-capsaicin. 
     
     
         311 . The method of any one of  claims 1 - 310 , wherein the patient does not expose area receiving a capsaicin dose to heat for a duration of at least 12 hours after administration of capsaicin. 
     
     
         312 . A method of ameliorating nerve pain in a human patient, comprising:
 a. applying for a duration of about 15 minutes a cooling article to a human patient's skin in proximity to an intermetatarsal neuroma in need of pain relief therapy, wherein the cooling article has an exterior surface temperature in the range of from about 5° C. to about 15° C. for application to the patient's foot; then   b. administering by injection into tissue adjacent to the intermetatarsal neuroma a pharmaceutical composition comprising a single pain-relief agent selected from the group consisting of lidocaine and a pharmaceutically acceptable salt thereof, in order to deliver a dose of lidocaine in an amount ranging from about 1 mg to about 50 mg;   c. applying for a duration of about 30 minutes a cooling article to the human patient's skin in proximity to the intermetatarsal neuroma in need of pain relief therapy, wherein the cooling article has an exterior surface temperature in the range of from about 5° C. to about 15° C. for application to the patient's foot; then   d. administering by injection into tissue adjacent to the intermetatarsal neuroma capsaicin in an amount of from about 100 μg to 300 μg; and then   e. applying for a duration of at least about 30 minutes a cooling article to the patient's skin in proximity to the intermetatarsal neuroma, wherein the cooling article has an exterior surface temperature in the range of from about 5° C. to about 15° C. for application to the patient's foot;
 to thereby ameliorate nerve pain in the human patient. 
   
     
     
         313 . A method of attenuating transient burning sensation due to injection of capsaicin into tissue adjacent to an intermetatarsal neuroma, comprising:
 a. applying for a duration of about 15 minutes a cooling article to a human patient's skin in proximity to an intermetatarsal neuroma in need of pain relief therapy, wherein the cooling article has an exterior surface temperature in the range of from about 5° C. to about 15° C. for application to the patient's foot; then   b. administering by injection into tissue adjacent to the intermetatarsal neuroma a pharmaceutical composition comprising a single pain-relief agent selected from the group consisting of lidocaine and a pharmaceutically acceptable salt thereof, in order to deliver a dose of lidocaine in an amount ranging from about 1 mg to about 50 mg;   c. applying for a duration of about 30 minutes a cooling article to the human patient's skin in proximity to the intermetatarsal neuroma in need of pain relief therapy, wherein the cooling article has an exterior surface temperature in the range of from about 5° C. to about 15° C. for application to the patient's foot; then   d. administering by injection into tissue adjacent to the intermetatarsal neuroma capsaicin in an amount of from about 100 μs to 300 μg; and then   e. applying for a duration of at least about 30 minutes a cooling article to the patient's skin in proximity to the intermetatarsal neuroma, wherein the cooling article has an exterior surface temperature in the range of from about 5° C. to about 15° C. for application to the patient's foot;
 to thereby ameliorate nerve pain in the human patient. 
   
     
     
         314 . A method of ameliorating nerve pain in a human patient, comprising:
 a. applying a cooling article to a human patient's skin in proximity to an intermetatarsal neuroma in need of pain relief therapy; then   b. administering by injection into tissue adjacent to the intermetatarsal neuroma a pharmaceutical composition comprising a single pain-relief agent selected from the group consisting of lidocaine and a pharmaceutically acceptable salt thereof, in order to deliver a dose of lidocaine in an amount ranging from about 1 mg to about 50 mg;   c. applying a cooling article to a human patient's skin in proximity to an intermetatarsal neuroma in need of pain relief therapy to achieve a temperature in the range of from about 26° C. to about 33° C. for tissue in proximity to the intermetatarsal neuroma;   d. administering by injection into tissue adjacent to the intermetatarsal neuroma capsaicin in an amount of from about 100 μg to 300 μg; and then   e. applying a cooling article to the human patient's skin in proximity to the intermetatarsal neuroma in need of pain relief therapy;
 to thereby ameliorate nerve pain in the human patient. 
   
     
     
         315 . A method of attenuating transient burning sensation due to injection of capsaicin into tissue adjacent to an intermetatarsal neuroma, comprising:
 a. applying a cooling article to a human patient's skin in proximity to an intermetatarsal neuroma in need of pain relief therapy; then   b. administering by injection into tissue adjacent to the intermetatarsal neuroma a pharmaceutical composition comprising a single pain-relief agent selected from the group consisting of lidocaine and a pharmaceutically acceptable salt thereof, in order to deliver a dose of lidocaine in an amount ranging from about 1 mg to about 50 mg;   c. applying a cooling article to a human patient's skin in proximity to an intermetatarsal neuroma in need of pain relief therapy to achieve a temperature in the range of from about 26° C. to about 33° C. for tissue in proximity to the intermetatarsal neuroma;   d. administering by injection into tissue adjacent to the intermetatarsal neuroma capsaicin in an amount of from about 100 μg to 300 μg; and then   e. applying a cooling article to the human patient's skin in proximity to the intermetatarsal neuroma in need of pain relief therapy;
 to thereby attenuate transient burning sensation due to injection of capsaicin into tissue in proximity to an intermetatarsal neuroma. 
   
     
     
         316 . The method of any one of  claims 312 - 315 , wherein the capsaicin is administered in the form of a pharmaceutical composition comprising capsaicin formulated for injection. 
     
     
         317 . The method of any one of  claim 1 - 311  or  316 , wherein the pharmaceutical composition comprising capsaicin further comprises water and a poly(ethylene glycol). 
     
     
         318 . The method of any one of  claim 1 - 311  or  316 , wherein the pharmaceutical composition comprising capsaicin consists essentially of water, capsaicin, and a poly(ethylene glycol). 
     
     
         319 . The method of  claim 317  or  318 , wherein the poly(ethylene glycol) has a number-average molecular weight of about 300 g/mol. 
     
     
         320 . The method of any one of  claims 317 - 319 , wherein the poly(ethylene glycol) is present in an amount of about 30% by weight of the pharmaceutical formulation. 
     
     
         321 . The method of any one of  claim 1 - 311  or  316 , wherein the pharmaceutical composition comprising capsaicin is an aqueous injectable formulation that comprises:
 a. about 0.03% (w/w) to about 0.3% (w/w) of capsaicin; 
 b. about 0.1% (w/w) to about 3% (w/w) of a solubilizing agent, wherein the solubilizing agent comprises (i) a polyethylene glycol ester of a (C 15 -C 25 ) hydroxyalkanoic acid, (ii) a polyethylene glycol ester of a (C 15 -C 25 ) hydroxyalkenoic acid, or (iii) a polyethylene glycol ester of a (C 15 -C 25 ) alkanoic acid substituted by a —OC(O)(C 14 -C 24 ) hydroxyalkyl group; 
 c. about 0.001% (w/w) to about 2% (w/w) of an antioxidant; and 
 d. at least 92% (w/w) water. 
 
     
     
         322 . The method of  claim 321 , wherein the formulation comprises about 0.5% (w/w) to about 1.5% (w/w) of the solubilizing agent. 
     
     
         323 . The method of  claim 321 , wherein the formulation comprises about 0.8% (w/w) to about 1.2% (w/w) of the solubilizing agent. 
     
     
         324 . The method of  claim 321 , wherein the formulation comprises about 1% (w/w) of the solubilizing agent. 
     
     
         325 . The method of  claim 321 , wherein the formulation comprises about 1.5% (w/w) to about 2.5% (w/w) of the solubilizing agent. 
     
     
         326 . The method of  claim 321 , wherein the formulation comprises about 2% (w/w) of the solubilizing agent. 
     
     
         327 . The method of any one of  claims 321 - 326 , wherein the solubilizing agent comprises a (C 14 -C 24 )hydroxyalkyl-CO 2 -(polyethylene glycolyl)-H and (C 14 -C 24 )hydroxyalkyl-CO 2 —(C 14 -C 24 )alkylene-CO 2 -(polyethylene glycolyl)-H. 
     
     
         328 . The method of any one of  claims 321 - 326 , wherein the solubilizing agent comprises a (C 14 -C 24 )hydroxyalkyl-CO 2 -(polyethylene glycolyl)-H, (C 14 -C 24 )hydroxyalkyl-CO 2 -(C 14 -C 24 )alkylene-CO 2 -(polyethylene glycolyl)-H, and polyethylene glycol. 
     
     
         329 . The method of any one of  claims 321 - 326 , wherein the solubilizing agent comprises (a) from about 60% (w/w) to about 80% (w/w) of a mixture of (C 14 -C 24 )hydroxyalkyl-CO 2 -(polyethylene glycolyl)-H and (C 14 -C 24 )hydroxyalkyl-CO 2 —(C 14 -C 24 )alkylene-CO 2 -(polyethylene glycolyl)-H, and (b) from about 20% (w/w) to about 40% (w/w) polyethylene glycol. 
     
     
         330 . The method of any one of  claims 321 - 326 , wherein the solubilizing agent comprises (a) about 70% (w/w) of a mixture of (C 14 -C 24 )hydroxyalkyl-CO 2 -(polyethylene glycolyl)-H and (C 14 -C 24 )hydroxyalkyl-CO 2 —(C 14 -C 24 )alkylene-CO 2 -(polyethylene glycolyl)-H, and (b) about 30% (w/w) polyethylene glycol. 
     
     
         331 . The method of any one of  claims 321 - 326 , wherein the solubilizing agent comprises (C 17 )hydroxyalkyl-CO 2 -(polyethylene glycolyl)-H and (C 17 )hydroxyalkyl-CO 2 —(C 17 )alkylene-CO 2 -(polyethylene glycolyl)-H. 
     
     
         332 . The method of any one of  claims 321 - 326 , wherein the solubilizing agent comprises (C 17 )hydroxyalkyl-CO 2 -(polyethylene glycolyl)-H, (Cr)hydroxyalkyl-CO 2 —(C 17 )alkylene-CO 2 -(polyethylene glycolyl)-H, and polyethylene glycol. 
     
     
         333 . The method of any one of  claims 321 - 326 , wherein the solubilizing agent comprises (a) from about 60% (w/w) to about 80% (w/w) of a mixture of (C 17 )hydroxyalkyl-CO 2 -(polyethylene glycolyl)-H and (C 17 )hydroxyalkyl-CO 2 —(C 17 )alkylene-CO 2 -(polyethylene glycolyl)-H, and (b) from about 20% (w/w) to about 40% (w/w) polyethylene glycol. 
     
     
         334 . The method of any one of  claims 321 - 326 , wherein the solubilizing agent comprises (a) about 70% (w/w) of a mixture of (Cr)hydroxyalkyl-CO 2 -(polyethylene glycolyl)-H and (C 17 )hydroxyalkyl-CO 2 —(C 17 )alkylene-CO 2 -(polyethylene glycolyl)-H, and (b) about 30% (w/w) polyethylene glycol. 
     
     
         335 . The method of any one of  claims 321 - 326 , wherein the solubilizing agent comprises 
       
         
           
           
               
               
           
         
       
     
     
         336 . The method of any one of  claims 321 - 326 , wherein the solubilizing agent is a mixture of 
       
         
           
           
               
               
           
         
       
       and polyethylene glycol. 
     
     
         337 . The method of any one of  claims 321 - 326 , wherein the solubilizing agent comprises (a) about 70% (w/w) of a mixture of 
       
         
           
           
               
               
           
         
       
       and (b) about 30% (w/w) polyethylene glycol. 
     
     
         338 . The method of any one of  claims 321 - 337 , wherein any polyethylene glycol or polyethylene glycolyl each independently have a weight-average molecular weight in the range of about 100 g/mol to about 3000 g/mol. 
     
     
         339 . The method of any one of  claims 321 - 337 , wherein any polyethylene glycol or polyethylene glycolyl each independently have a weight-average molecular weight in the range of about 200 g/mol to about 1000 g/mol. 
     
     
         340 . The method of any one of  claims 321 - 337 , wherein any polyethylene glycol or polyethylene glycolyl each independently have a weight-average molecular weight in the range of about 300 g/mol to about 900 g/mol. 
     
     
         341 . The method of any one of  claims 321 - 337 , wherein any polyethylene glycol or polyethylene glycolyl each independently have a weight-average molecular weight in the range of about 500 g/mol to about 800 g/mol. 
     
     
         342 . The method of any one of  claims 321 - 337 , wherein any polyethylene glycol or polyethylene glycolyl each independently have a weight-average molecular weight in the range of about 600 g/mol to about 750 g/mol. 
     
     
         343 . The method of any one of  claims 321 - 342 , wherein the formulation comprises about 0.005% (w/w) to about 0.1% (w/w) of the antioxidant. 
     
     
         344 . The method of any one of  claims 321 - 342 , wherein the formulation comprises about 0.01% (w/w) of the antioxidant. 
     
     
         345 . The method of any one of  claims 321 - 344 , wherein the antioxidant is an organic compound. 
     
     
         346 . The method of any one of  claims 321 - 344 , wherein the antioxidant is dibutylhydroxytoluene. 
     
     
         347 . The method of any one of  claims 321 - 346 , further comprising a chelating agent. 
     
     
         348 . The method of any one of  claims 321 - 346 , further comprising about 0.001% (w/w) to about 0.5% (w/w) of a chelating agent. 
     
     
         349 . The method of any one of  claims 321 - 346 , further comprising about 0.01% (w/w) to about 0.05% (w/w) of a chelating agent. 
     
     
         350 . The method of any one of  claims 321 - 346 , further comprising about 0.025% (w/w) of a chelating agent. 
     
     
         351 . The method of any one of  claims 347 - 350 , wherein the chelating agent is an aliphatic amine compound containing at least two carboxylic acid groups. 
     
     
         352 . The method of any one of  claims 347 - 350 , wherein the chelating agent is ethylenediaminetetraacetic acid or a salt thereof. 
     
     
         353 . The method of any one of  claims 321 - 352 , further comprising a buffer. 
     
     
         354 . The method of  claim 353 , wherein the buffer comprises a carboxylic acid compound having a molecular weight less than 500 g/mol, a salt thereof, or a mixture thereof. 
     
     
         355 . The method of  claim 353 , wherein the buffer comprises a C 1 -C 6  alkanoic acid, a salt thereof, or a mixture thereof. 
     
     
         356 . The method of  claim 353 , wherein the buffer comprises acetic acid, a salt of acetic acid, or a mixture thereof. 
     
     
         357 . The method of any one of  claims 321 - 356 , further comprising a tonicity modifier. 
     
     
         358 . The method of any one of  claims 321 - 356 , further comprising about 0.01% (w/w) to about 5% (w/w) of a tonicity modifier. 
     
     
         359 . The method of any one of  claims 321 - 356 , further comprising about 0.1% (w/w) to about 2% (w/w) of a tonicity modifier. 
     
     
         360 . The method of any one of  claims 321 - 356 , further comprising about 0.3% (w/w) to about 0.9% (w/w) of a tonicity modifier. 
     
     
         361 . The method of any one of  claims 357 - 360 , wherein the tonicity modifier is an alkali metal salt. 
     
     
         362 . T The method of any one of  claims 357 - 360 , wherein the tonicity modifier is sodium chloride. 
     
     
         363 . The method of any one of  claims 357 - 360 , wherein the tonicity modifier is a monosaccharide. 
     
     
         364 . The method of any one of  claims 357 - 360 , wherein the tonicity modifier is dextrose. 
     
     
         365 . The method of any one of  claims 321 - 364 , wherein the formulation comprises at least 95% (w/w) water. 
     
     
         366 . The method of any one of  claims 321 - 364 , wherein the formulation comprises from about 95% (w/w) to about 99% (w/w) water. 
     
     
         367 . The method of any one of  claims 321 - 364 , wherein the formulation comprises from about 97% (w/w) to about 98% (w/w) water. 
     
     
         368 . The method of any one of  claims 321 - 364 , wherein the formulation has a pH in the range of about 4 to about 7. 
     
     
         369 . The method of any one of  claims 321 - 364 , wherein the formulation has a pH in the range of about 5 to about 6. 
     
     
         370 . The method of any one of  claims 321 - 364 , wherein the formulation has a pH of about 5.5. 
     
     
         371 . The method of any one of  claims 321 - 370 , wherein the formulation comprises from about 0.03% (w/w) to about 0.15% (w/w) of capsaicin. 
     
     
         372 . The method of any one of  claims 321 - 370 , wherein the formulation comprises from about 0.03% (w/w) to about 0.07% (w/w) of capsaicin. 
     
     
         373 . The method of any one of  claims 321 - 370 , wherein the formulation comprises about 0.05% (w/w) of capsaicin. 
     
     
         374 . The method of any one of  claims 321 - 370 , wherein the formulation comprises from about 0.08% (w/w) to about 0.12% (w/w) of capsaicin. 
     
     
         375 . The method of any one of  claims 321 - 370 , wherein the formulation comprises about 0.1% (w/w) of capsaicin. 
     
     
         376 . The method of  claim 321 , wherein the aqueous injectable formulation comprises:
 a. about 0.04% (w/w) to about 0.06% (w/w) of capsaicin;   b. about 0.5% (w/w) to about 1.5% (w/w) of a solubilizing agent, wherein the solubilizing agent comprises   
       
         
           
           
               
               
           
         
       
       and polyethylene glycol;
 c. about 0.005% (w/w) to about 0.015% (w/w) of an antioxidant; 
 d. about 0.2% (w/w) to about 1% (w/w) of an alkali metal acetate; 
 e. about 0.01% (w/w) to about 0.05% (w/w) of a chelating agent; 
 f about 0.3% (w/w) to about 0.9% (w/w) of a tonicity modifier; 
 g. at least 96% (w/w) water; and 
 having a pH in the range of about 5 to about 6. 
 
     
     
         377 . The method of  claim 321 , wherein the aqueous injectable formulation comprises:
 a. about 0.04% (w/w) to about 0.06% (w/w) of capsaicin;   b. about 0.8% (w/w) to about 1.2% (w/w) of a solubilizing agent, wherein the solubilizing agent comprises   
       
         
           
           
               
               
           
         
       
       and polyethylene glycol;
 c. about 0.005% (w/w) to about 0.015% (w/w) of dibutylhydroxytoluene; 
 d. about 0.2% (w/w) to about 1% (w/w) of sodium acetate; 
 e. about 0.01% (w/w) to about 0.05% (w/w) of ethylenediaminetetraacetic acid or a salt thereof; 
 f about 0.3% (w/w) to about 0.9% (w/w) of sodium chloride; 
 g. at least 96% (w/w) water; and 
 having a pH in the range of about 5 to about 6. 
 
     
     
         378 . The method of  claim 321 , wherein the aqueous injectable formulation comprises:
 a. about 0.04% (w/w) to about 0.06% (w/w) of capsaicin;   b. about 0.8% (w/w) to about 1.2% (w/w) of a solubilizing agent, wherein the solubilizing agent comprises (a) about 70% (w/w) of a mixture of   
       
         
           
           
               
               
           
         
       
       and (b) about 30% (w/w) polyethylene glycol;
 c. about 0.005% (w/w) to about 0.015% (w/w) of dibutylhydroxytoluene; 
 d. about 0.2% (w/w) to about 1% (w/w) of sodium acetate; 
 e. about 0.01% (w/w) to about 0.05% (w/w) of ethylenediaminetetraacetic acid or a salt thereof; 
 f about 0.3% (w/w) to about 0.9% (w/w) of sodium chloride; 
 g. at least 96% (w/w) water; and 
 having a pH in the range of about 5 to about 6. 
 
     
     
         379 . The method of  claim 321 , wherein the aqueous injectable formulation comprises:
 a. about 0.05% (w/w) of capsaicin;   b. about 1% (w/w) of a solubilizing agent, wherein the solubilizing agent comprises   
       
         
           
           
               
               
           
         
       
       and polyethylene glycol;
 c. about 0.005% (w/w) to about 0.015% (w/w) of dibutylhydroxytoluene; 
 d. about 0.2% (w/w) to about 1% (w/w) of sodium acetate; 
 e. about 0.01% (w/w) to about 0.05% (w/w) of ethylenediaminetetraacetic acid or a salt thereof; 
 f about 0.3% (w/w) to about 0.9% (w/w) of sodium chloride; 
 g. at least 96% (w/w) water; and 
 having a pH of about 5.5. 
 
     
     
         380 . The method of any one of  claims 376 - 379 , wherein the solubilizing agent comprises (a) from 68% (w/w) to 72% (w/w) of a mixture of 
       
         
           
           
               
               
           
         
       
       and (b) from 28% (w/w) to 32% (w/w) polyethylene glycol. 
     
     
         381 . The method of any one of  claims 376 - 379 , wherein any polyethylene glycol or polyethylene glycolyl each independently have a weight-average molecular weight in the range of about 300 g/mol to about 900 g/mol. 
     
     
         382 . The method of any one of  claims 376 - 379 , wherein any polyethylene glycol or polyethylene glycolyl each independently have a weight-average molecular weight in the range of about 500 g/mol to about 800 g/mol. 
     
     
         383 . The method of any one of  claims 376 - 379 , wherein any polyethylene glycol or polyethylene glycolyl each independently have a weight-average molecular weight in the range of about 600 g/mol to about 750 g/mol. 
     
     
         384 . The method of any one of  claims 321 - 380 , wherein any polyethylene glycolyl has a weight-average molecular weight of about 660 g/mol. 
     
     
         385 . The method of any one of  claims 1 - 384 , wherein the capsaicin is a mixture of cis and trans isomers that contains at least 97% by weight trans-capsaicin. 
     
     
         386 . The method of any one of  claims 1 - 384 , the capsaicin is a mixture of cis-capsaicin and trans-capsaicin that contains at least 99% by weight trans-capsaicin. 
     
     
         387 . The method of any one of  claims 1 - 384 , wherein the capsaicin consists essentially of the trans isomer. 
     
     
         388 . The method of any one of  claims 1 - 387 , wherein the patient has an age in the range of about 20 to about 30 years old, about 30 to about 40 years old, about 40 to about 50 years old, about 50 to about 60 years old, or about 60 to about 70 years old, or an age greater than 70 years old. 
     
     
         389 . The method of any one of  claims 1 - 387 , wherein the patient is an adult human male, or an adult human female. 
     
     
         390 . The method of any one of  claims 1 - 387 , wherein the patient is an pediatric human. 
     
     
         391 . The method of any one of  claims 1 - 390 , wherein the patient has a body mass index less than or equal to 45 kg/m 2 . 
     
     
         392 . The method of any one of  claims 1 - 390 , wherein the patient has a body mass index in the range of from about 18 kg/m 2  to about 32 kg/m 2 .