title: Neurotrophin-3 attenuates galanin expression in the chronic constriction injury model of neuropathic pain.
abstract: We have recently shown that exogenous neurotrophin-3 (NT-3) acts antagonistically to nerve growth factor (NGF) in regulation of nociceptor phenotype in intact neurons and suppresses thermal hyperalgesia and expression of molecules complicit in this behavioral response induced by chronic constriction injury (CCI) of the sciatic nerve. The present study examines whether there is a global influence of NT-3 in mitigating alterations in peptide and NGF receptor expression; molecules believed to also contribute to CCI-associated pain. Thus, the influence of NT-3 on phenotypic changes in dorsal root ganglion (DRG) neurons in rats coincident with CCI was examined using in situ hybridization. Seven days following injury, the incidence of expression of the neuropeptides galanin and pituitary adenylate cyclase-activating polypeptide (PACAP) was increased in L5 sensory neurons ipsilateral to the injury from 12% to 60% and 16% to 37% respectively, in addition to an increased level of expression. In contrast, there was no consistent significant change in tropomyosin-related kinase A (trkA) expression following CCI. Intrathecal infusion of NT-3 globally mitigated both the increased incidence and elevated levels of galanin messenger RNA (mRNA) expression observed following CCI, reducing the former from 60% to 39%. NT-3 infusion resulted in a limited reduction in the incidence and level of neuronal PACAP in medium to large size, but not small size, DRG neurons. NT-3 had no significant net effect on CCI-induced alterations in trkA mRNA expression.
authors.affiliation: Department of Anatomy and Cell Biology, Cameco MS Neuroscience Research Center, University of Saskatchewan, 701 Queen Street, Saskatoon, Saskatchewan, Canada S7N 5E5.
authors.forename: T D
authors.initials: TD
authors.lastname: Wilson-Gerwing
authors.forename: V M K
authors.initials: VM
authors.lastname: Verge
mesh_terms: D000818:Animals; D003250:Constriction; D004195:Disease Models, Animal; D019004:Galanin / Q000235:genetics / Q000378:metabolism*; D005786:Gene Expression Regulation / Q000187:drug effects*; D017403:In Situ Hybridization / Q000379:methods; D008297:Male; D020933:Neurotrophin 3 / Q000494:pharmacology*; D051219:Pituitary Adenylate Cyclase-Activating Polypeptide / Q000235:genetics / Q000378:metabolism; D012333:RNA, Messenger / Q000378:metabolism; D051381:Rats; D017208:Rats, Wistar; D020917:Receptor, trkA / Q000235:genetics / Q000378:metabolism; D012585:Sciatica / Q000188:drug therapy / Q000378:metabolism* / Q000473:pathology
chemical_list: D020933:Neurotrophin 3; D051219:Pituitary Adenylate Cyclase-Activating Polypeptide; D012333:RNA, Messenger; D019004:Galanin; D020917:Receptor, trkA