Systems, compositions, and methods for local imaging and treatment of pain

Abstract

Pain factors are labeled with targeted agents or markers delivered into the body. The labeled pain factors are imaged with appropriate imaging tools in a manner allowing selective identification and localization of areas of pain source or transmission. The labeled pain factors allow spatial differentiation in the imaging sufficient to specify the location of the pain so as to drive therapeutic decisions and techniques in order to treat the pain. Pain factors labeled and imaged in this manner may include one or more of nerve factors, blood vessel factors, cellular factors, and inflammation factors. Labeled markers may include for example radioactive materials (e.g. tritiated or iodinated molecules) or other materials such as metal (e.g. gold) nanoparticles. Intermediary binding materials may be used, such as for example bi-specific antibodies.

1 . (canceled) 
     
     
         2 . A method for conducting a medical procedure on an intervertebral disc of a spine in a body of a discogenic back pain patient, comprising:
 providing a substantially targeted agent that is adapted to differentially bind to a pain factor;   conjugating the targeted agent with an imaging contrast label to thereby form a targeted label configured to label the pain factor via the bound pain factor-label conjugate;   locally injecting into a first disc, using a local injection assembly, the targeted label in a manner that is adapted to differentially bind to and label the pain factor in a first region of tissue at a first location in the first disc;   locally injecting into a second said disc, using a local injection assembly, the targeted label in a manner that is adapted to differentially bind to and label the pain factor in a second region of tissue at a second location in the second disc;   binding the pain factor at the first and second locations with the injected targeted label, thereby artificially labeling the pain factor with the targeted label at the first and second locations in a manner substantially increasing the ability to image the pain factor with an imaging tool;   imaging the first and second discs with the imaging tool in a manner sufficient to selectively differentiate a first relative concentration of the labeled pain factor at the first location relative to a second relative concentration of the labeled pain factor in the second region of tissue at the second location;   wherein imaging the labeled pain factor comprises using the imaging tool to image the label coupled to the pain factor via the bound targeted agent, and the first and second relative concentrations are a function of relative amounts of the label at the first and second locations;   wherein the pain factor located in the first or second regions comprises a cyclooxygenase-2 (COX-2) factor comprising a COX-2 molecule or an analog, derivative, precursor, binding agent, or antibody thereof;   wherein the targeted agent comprises a COX-2 factor binding agent or antibody, or a binding agent or antibody of a COX-2 factor binding agent or antibody located in the first or second respective regions; and   diagnosing the first and second locations as relatively painful versus non-painful by comparing the selectively differentiated first and second relative concentrations.   
     
     
         3 . The method of  claim 2 , wherein the pain factor comprises an NF-κβ pathway factor. 
     
     
         4 . The method of  claim 2 , wherein the pain factor comprises a prostaglandin pathway factor. 
     
     
         5 . The method of  claim 2 , wherein the pain factor comprises a nitric oxide factor comprising a nitric oxide molecule or an analog, derivative, precursor, or binding agent thereof. 
     
     
         6 . The method of  claim 5 , wherein the pain factor comprises an interleukin that comprises IL-1, or an analog or derivative or precursor thereof, and the targeted label comprises a binding agent or antibody thereof. 
     
     
         7 . The method of  claim 5 , wherein the pain factor comprises TNF-alpha and the targeted label comprises a binding agent or antibody thereof. 
     
     
         8 . The method of  claim 2 , wherein the targeted label comprises a radioactive material. 
     
     
         9 . The method of  claim 8 , wherein the targeted label comprises a radio-labeled COX-2 factor antibody or an analog or derivative thereof, or radiolabeled iodine. 
     
     
         10 . The method of  claim 8 , wherein the targeted label comprises a radiolabeled iodine that comprises I-125. 
     
     
         11 . The method of  claim 2 , further comprising imaging the labeled pain factor using an imaging tool that comprises a phosphor imaging plate. 
     
     
         12 . The method of  claim 2 , further comprising:
 prior to the step of injecting the targeted agent into the region of tissue at the location, delivering a first binding agent, which comprises a binding agent or antibody of the COX-2 factor or of an analog or derivative or precursor of the COX-2 factor, into the patient's body in a manner that is adapted to bind to the COX-2 factor or analog or derivative or precursor thereof, and allowing the first binding agent to bind to the COX-2 factor or analog or derivative or precursor thereof at the first location; and   wherein the targeted agent is adapted to bind to a site located on the bound combination of the first binding agent and the COX-2 factor or analog or derivative or precursor thereof.   
     
     
         13 . The method of  claim 12 , wherein:
 the first binding agent comprises a bi-specific antibody with a first binding site adapted to bind to the COX-2 factor and a second binding site adapted to bind to the targeted agent comprising the targeted label.   
     
     
         14 . The method of  claim 2 , wherein:
 the targeted label comprises a cell bound to an antibody or binding agent having an exposed binding site that is adapted to bind to the COX-2 factor.   
     
     
         15 . The method of  claim 2 , further comprising:
 conducting a therapeutic procedure in a substantially localized manner to the location where the targeted labeled pain factor is locally imaged.   
     
     
         16 . The method of  claim 15 , wherein the therapeutic procedure is adapted to substantially alleviate generation or transmission of pain at the first location. 
     
     
         17 . The method of  claim 15 , wherein the therapeutic procedure is adapted to substantially ablate at least one nerve at the first location. 
     
     
         18 . The method of  claim 15 , wherein the therapeutic procedure comprises delivering at least one therapeutic chemical in a substantially localized manner to the location. 
     
     
         19 . The method of  claim 15 , wherein the therapeutic procedure comprises:
 delivering a therapeutic dose of energy in a substantially localized manner to the first location.   
     
     
         20 . The method of  claim 19 , wherein the therapeutic procedure further comprises:
 ablating at least one nerve at the first location with the therapeutic dose of energy.   
     
     
         21 . The method of  claim 19 , wherein the therapeutic dose delivery of energy in the substantially localized manner to the first location further comprises:
 delivering ultrasound energy to the first location.   
     
     
         22 . The method of  claim 21 , wherein the ultrasound energy delivery further comprises:
 delivering the ultrasound energy in a directed manner locally into the first location from a delivery location.   
     
     
         23 . The method of  claim 22 , wherein:
 the delivery location is outside of the patient; and   the ultrasound energy is delivered via high intensity focused ultrasound (HIFU) that is adapted to focus the ultrasound energy to the location.   
     
     
         24 . The method of  claim 22 , wherein:
 the delivery location is adjacent to the first location within the patient; and   the ultrasound energy is delivered via a directional ultrasound probe.   
     
     
         25 . The method of  claim 24 , wherein:
 the delivery location is adjacent to an intervertebral disc and the first location receiving the directional ultrasound therapy is within the intervertebral disc.   
     
     
         26 . The method of  claim 19 , wherein the therapeutic dose of energy comprises thermal energy. 
     
     
         27 . The method of  claim 26 , further comprising delivering the therapeutic dose of electrical energy via a radiofrequency (RF) probe. 
     
     
         28 . The method of  claim 2 , wherein the first region of tissue comprises only a portion that is less than all of the intervertebral disc. 
     
     
         29 . The method of  claim 28 , wherein the portion is less than or equal to about one-half of the intervertebral disc. 
     
     
         30 . The method of  claim 29 , wherein the portion is located within less than or equal to an about one-hundred eighty degree angular circumferential region of the disc in a transverse plane relative to the spine. 
     
     
         31 . The method of  claim 29 , wherein the portion is less than or equal to about one-quarter of the intervertebral disc. 
     
     
         32 . The method of  claim 31 , wherein the portion is located within less than or equal to an about ninety degree angular circumferential region of the disc in a transverse plane relative to the spine. 
     
     
         33 . The method of  claim 2 , wherein the location comprises an end-plate associated with a vertebral body. 
     
     
         34 . The method of  claim 2 , further comprising:
 using a local injection assembly to inject the targeted agent into a third intervertebral disc in the spine of the patient and which comprises a third region of tissue at a third location;   binding the pain factor at the third location with the targeted agent injected into the third disc, thereby artificially labeling the pain factor with the targeted label at the third location in a manner substantially increasing the ability to image the pain factor at the third location with the imaging tool; and   wherein the labeled pain factor imaging step further comprises imaging the third intervertebral disc to thereby image a third concentration in the third region of tissue at the third location.   
     
     
         35 . The method of  claim 34 , further comprising:
 conducting at least one therapeutic procedure in a substantially localized manner to each of the first and third locations where the targeted labeled pain factor is locally and selectively imaged.   
     
     
         36 . The method of  claim 2 , wherein the targeted label comprises a nanoparticle. 
     
     
         37 . The method of  claim 2 , wherein the targeted label comprises at least one of gold or iron oxide. 
     
     
         38 . The method of  claim 2 , wherein the targeted label comprises an MRI contrast agent. 
     
     
         39 . The method of  claim 38 , wherein the MRI contrast agent comprises gadolinium. 
     
     
         40 . The method of  claim 38 , further comprising MRI imaging an area of increased concentration of the MRI contrast agent bound to the pain factor via the targeted agent. 
     
     
         41 . The method of  claim 2  wherein the targeted label comprises an ultrasound contrast agent. 
     
     
         42 . The method of  claim 41 , further comprising ultrasonically imaging an area of increased concentration of the ultrasound contrast agent bound to the pain factor via the targeted agent. 
     
     
         43 . The method of  claim 2 , wherein the targeted label comprises a radiographic contrast agent. 
     
     
         44 . The method of  claim 43 , further comprising imaging an area of increased concentration of the radiographic contrast agent bound to the pain factor via the targeted agent using X-ray. 
     
     
         45 . The method of  claim 2 , further comprising imaging the first and second locations of the conjugated targeted agent bound to the pain factor in a manner that enhances the directed delivery of localized therapy to the first location. 
     
     
         46 . The method of  claim 2 , further comprising delivering the targeted agent into the patient via the patient's respiratory system. 
     
     
         47 . The method of  claim 2 , wherein the imaging contrast label used to conjugate the targeted agent comprises a nanoparticle. 
     
     
         48 . The method of  claim 2 , wherein the imaging contrast label used to conjugate the targeted agent comprises at least one of gold or iron oxide. 
     
     
         49 . The method of  claim 48 , wherein imaging contrast label used to conjugate the targeted agent comprises a magnetic resonance imaging (MRI) contrast agent. 
     
     
         50 . The method of  claim 49 , wherein the MRI contrast agent comprises gadolinium. 
     
     
         51 . The method of  claim 49 , wherein imaging the labeled pain factor comprises:
 using an MRI scanner to image the MRI contrast agent coupled to the pain factor via the bound targeted agent.   
     
     
         52 . The method of  claim 2 , wherein the imaging contrast label comprises an ultrasound contrast agent. 
     
     
         53 . The method of  claim 52 , wherein imaging the labeled pain factor comprises:
 ultrasonically imaging the ultrasound contrast agent label coupled to the pain factor via the targeted agent.   
     
     
         54 . The method of  claim 2 , wherein the imaging contrast label used to conjugate the targeted agent comprises a radiographic contrast agent. 
     
     
         55 . The method of  claim 54 , wherein imaging the labeled pain factor comprises:
 X-ray imaging the radiographic contrast agent coupled to the pain factor via the bound targeted agent.