Methods and kits for treating pain

Abstract

The present disclosure provides methods and kits for treating pain. More particularly, the present disclosure relates to methods of using PD-L1/PD-1-associated compounds to treat pain and/or bone destruction from bone cancer, and associated kits. The present disclosure also provides methods to assess the efficacy of compounds to suppress PD-1-associated nociceptive neuron activity.

1 . A method of treating a subject suffering from pain, the method comprising administering to the subject a therapeutically effective amount of a compound capable of suppressing PD-1-associated nociceptive neuron activity such that the pain is treated, wherein the compound comprises one or more of a small molecular activator of PD-1 and a SHP-1 phosphatase activator. 
     
     
         2 - 3 . (canceled) 
     
     
         4 . The method according to  claim 1 , wherein the compound is administered to the subject's dorsal root ganglia, skin, muscle, joint or cerebral spinal fluid (CSF). 
     
     
         5 . The method according to  claim 1 , further comprising administering to the subject a pain reliever simultaneously or serially. 
     
     
         6 . The method according to  claim 5 , wherein the pain reliever is morphine. 
     
     
         7 . A method of determining the efficacy of PD-1-associated nociceptive neuron activity suppression in a subject, the method comprising:
 a. administering to the subject a therapeutically effective amount of a compound capable of suppressing PD-1-associated nociceptive neuron activity, wherein the compound comprises one or more of a small molecular activator of PD-1 and a SHP-1 phosphatase activator; and   b. conducting one or more quantitative sensory test(s) on the subject, wherein the one or more quantitative sensory test(s) is administered immediately after administration of the compound, and at one or more time points after administration of the compound, wherein a rapid change in mechanical pain sensitivity after administration of the compound indicates target engagement and efficacy of the therapy.   
     
     
         8 . (canceled) 
     
     
         9 . The method according to  claim 7 , wherein the one or more time points after administration of said compound is 30 minutes, 45 minutes, 1 hour, 2 hours, 3 hours, 6 hours and/or 12 hours after administration of said compound. 
     
     
         10 - 11 . (canceled) 
     
     
         13 . A kit for the treatment of pain in a subject, the kit comprising:
 a. a therapeutically effective amount of a compound capable of suppressing PD-1-associated nociceptive neuron activity, wherein the compound comprises one or more of a small molecular activator of PD-1 and a SHP-1 phosphatase activator;   b. an apparatus for administering said compound; and   c. instructions for use.   
     
     
         14 . (canceled) 
     
     
         15 . The method according to  claim 1 , wherein the subject is a human. 
     
     
         16 . The method according to  claim 7 , wherein the subject is a human. 
     
     
         17 . The kit according to  claim 13 , wherein the subject is a human. 
     
     
         18 . The method according to  claim 1 , further comprising administering to the subject a PD-L1 protein. 
     
     
         19 . The method according to  claim 7 , further comprising administering to the subject a PD-L1 protein. 
     
     
         20 . The kit according to  claim 13 , wherein the compound further comprises a PD-L1 protein.