Publisher Summary This chapter discusses the changes in expression of the orphan G-protein coupled receptor GPR7 in human painful peripheral neuropathies. Genomics has generated thousands of potential targets. Among these targets are the orphan 7 transmembrane receptors (GPCRs). GPCRs are already well established as a class of fruitful drug targets. The chapter presents a strategy to validate new targets expressed in the peripheral nervous system after injury, as candidate pain and nerve repair targets involved in the pathogenesis or the progression of human painful inflammatory peripheral neuropathies. The peripheral neuropathies that are accompanied by neuropathic pain sensations are usually thought to include cases of trauma (for example causalgia and phantom pain), postherpetic neuralgia, and painful diabetic neuropathy. Overexpression of GPR7 in Schwann cells from patients with inflammatory peripheral neuropathies and from animal models of inflammatory peripheral neuropathies is described. The expression of GPR7 into Schwann cells may represent the sum of two competing influences in inflammatory neuropathy: the generation of new axon signals after injury and stimulatory cytokines or other factors secreted by macrophages that may induce the expression of GPR7 in Schwann cells. Tumor necrosis factor alpha (TNFalpha) plays a key role in promoting changes in gene expression after tissue damage due to trauma or disease.