Methods and Materials for Determining Pain Sensitivity and Predicting and Treating Related Disorders

Abstract

Methods of treating somatosensory disorders and modulating production of proinflammatory cytokines by administering to a subject an effective amount of a COMT modulator, ADRB2 modulator, ADRB3 modulator or combinations thereof are provided. Methods of predicting effective pharmacological therapies for a subject afflicted with a somatosensory disorder by determining a genotype of the subject with regard to a gene selected from the group consisting of COMT, ADRB2, ADRB3, and combinations thereof are further provided. Methods of determining pain responses or pain perception and predicting susceptibility of a subject to develop related disorders, such as somatosensory disorders and somatization, by determining a genotype of the subject with regard to a gene selected from the group consisting of COMT, ADRB2, ADRB3, and combinations thereof are further provided.

1 - 29 . (canceled) 
     
     
         30 . A method of selecting a therapy for a human subject having a somatosensory disorder, comprising: (a) obtaining a DNA sample from the subject; (b) determining from the DNA sample a genotype of the subject with respect to a COMT gene, wherein the COMT genotype comprises a low pain sensitive haplotype (LPS), average pain sensitive haplotype (APS), high pain sensitive haplotype (HPS), or a combination thereof; and (c) selecting a β 2 -adrenergic receptor (ADRB2) antagonist therapy and/or β 3 -adrenergic receptor (ADRB3) antagonist therapy for the subject based on the determined COMT genotype of the subject. 
     
     
         31 . The method of  claim 30 , wherein the method further comprises determining from the DNA sample an ADRB2 genotype, wherein the ADRB2 genotype comprises Haplotype 1, Haplotype 2, Haplotype 3, Uncommon, or a combination thereof. 
     
     
         32 . The method of  claim 30 , wherein the method further comprises determining from the DNA sample an ADRB3 genotype, wherein the ADRB3 genotype comprises Haplotype 1, Haplotype 2, Haplotype 3, and Uncommon, or a combination thereof. 
     
     
         33 - 34 . (canceled) 
     
     
         35 . The method of  claim 31 , wherein the determined genotype of the subject with respect to ADRB2 comprises two copies of Haplotype 2, two copies of Haplotype 3, or one copy of both Haplotype 2 and Haplotype 3. 
     
     
         36 . The method of  claim 32 , wherein the determined genotype of the subject with respect to ADRB3 comprises two copies of Haplotype 1. 
     
     
         37 . The method of  claim 31 , wherein the determined genotype of the subject with respect to COMT comprises two copies of APS, two copies of HPS, or one copy of both APS and HPS. 
     
     
         38 - 39 . (canceled) 
     
     
         40 . The method of  claim 30 , wherein the somatosensory disorder is selected from the group consisting of chronic pain conditions, fibromyalgia syndrome, tension headache, migraine headache, phantom limb sensations, irritable bowel syndrome, chronic lower back pain, chronic fatigue, multiple chemical sensitivities, temporomandibular joint disorder, post-traumatic stress disorder, chronic idiopathic pelvic pain, Gulf War Syndrome, vulvar vestibulitis, osteoarthritis, rheumatoid arthritis, and angina pectoris. 
     
     
         41 - 78 . (canceled) 
     
     
         79 . The method of  claim 30 , wherein the somatosensory disorder is temporomandibular joint disorder. 
     
     
         80 . The method of  claim 30 , wherein determining the COMT genotype comprises determining an allele present at single nucleotide polymorphism (SNP) rs6269, SNP rs4633, SNP rs4818 and SNP rs4680. 
     
     
         81 . The method of  claim 30 , wherein the ADRB2 antagonist therapy comprises propranolol, sotalol, timolol, carteolol, carvedilol, nadolol, penbutolol, labetalol, pindolol, butoxamine, H35/25 or estrogen. 
     
     
         82 . The method of  claim 30 , wherein the ADRB3 antagonist therapy comprises L 748337, CL 316234 or SR 59230A.