title: The c-kit signaling pathway is involved in the development of persistent pain.
abstract: Protein kinase signal transduction pathways play critical roles in regulating nociception. Here we show that c-kit, a tyrosine kinase receptor, is expressed in lamina I and II layer of the dorsal horn. Moreover, the superficial c-kit(+) fibers originate from the dorsal root ganglion, and c-kit in lamina II inner layer comes from intrinsic expression of the spinal cord. Kit(W-v) mice, which contain a hypomorphic mutation, exhibited normal acute pain in most pain behavior tests. In the formalin test, the first phase was not affected, whereas the second phase pain response of Kit(W-v) mice was significantly reduced relative to wild-type littermates. Kit(W-v) mice also showed abnormal neuropathic pain, notably in the contralateral side of nerve injury. The expression and release of CGRP and substance P were not altered by the c-kit mutation. Together, these results implicate c-kit-mediated signal transduction in the development of persistent pain.
authors.affiliation: Washington University Pain Center and Department of Anesthesiology, Washington University School of Medicine, St. Louis, MO 63110, USA.
authors.forename: Yan-Gang
authors.initials: YG
authors.lastname: Sun
authors.forename: Neilia G
authors.initials: NG
authors.lastname: Gracias
authors.forename: Julie Kosto
authors.initials: JK
authors.lastname: Drobish
authors.forename: Michael R
authors.initials: MR
authors.lastname: Vasko
authors.forename: Robert W
authors.initials: RW
authors.lastname: Gereau
authors.forename: Zhou-Feng
authors.initials: ZF
authors.lastname: Chen
mesh_terms: D000704:Analysis of Variance; D000818:Animals; D015740:Calcitonin Gene-Related Peptide / Q000235:genetics / Q000378:metabolism; D003251:Constriction, Pathologic / Q000150:complications; D005260:Female; D005727:Ganglia, Spinal / Q000166:cytology; D006930:Hyperalgesia / Q000145:classification / Q000235:genetics / Q000503:physiopathology*; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D009474:Neurons / Q000378:metabolism; D010146:Pain / Q000209:etiology* / Q000235:genetics / Q000378:metabolism* / Q000473:pathology; D010147:Pain Measurement / Q000379:methods; D010812:Physical Stimulation / Q000379:methods; D017354:Point Mutation / Q000235:genetics; D019009:Proto-Oncogene Proteins c-kit / Q000235:genetics / Q000378:metabolism*; D011863:Radioimmunoassay / Q000379:methods; D019051:Rhizotomy / Q000009:adverse effects; D015398:Signal Transduction / Q000502:physiology*; D013116:Spinal Cord / Q000378:metabolism; D013373:Substance P / Q000235:genetics / Q000378:metabolism
chemical_list: D013373:Substance P; D019009:Proto-Oncogene Proteins c-kit; D015740:Calcitonin Gene-Related Peptide