title: Role of Nectin-1/c-Src Signaling in the Analgesic Effect of GDNF on a Rat Model of Chronic Constrictive Injury.
abstract: Neuropathic pain results from nerve injury and is one of the most refractory disorders. Recently, many studies reported that glial cell-derived neurotrophic factor (GDNF) exhibited potent analgesic effects, but the underlying mechanisms still remain unknown. In addition to the classical GDNF-GFRα1-Ret pathway, GDNF can bind to adhesion proteins such as E-cadherin and NCAM via GFRα1 in a Ret-independent way. In this study, we aimed to examine whether the adhesion protein nectin-1 and its downstream protein c-Src are involved in neuropathic pain. We found that nectin-1 was expressed in the superficial dorsal horn of the spinal cord and that it was increased after chronic constrictive injury (CCI). Intrathecal administration of nectin-1 siRNA attenuated neuropathic pain induced by CCI via interference of the expression of nectin-1. Furthermore, we found that GDNF can downregulate the phosphorylation level of nectin-1-associated c-Src without changing the expression level of nectin-1. In summary, these data suggest that nectin-1 is involved in neuropathic pain, and that GDNF exerts analgesic effects by directly or indirectly regulating nectin-1/c-Src signaling. These findings may lead to a new target for the treatment of neuropathic pain.
authors.affiliation: Jiangsu Province Key Laboratory of Anesthesiology, Xuzhou Medical College, Xuzhou, Jiangsu, 221004, China.|Jiangsu Province Key Laboratory of Anesthesia and Analgesia Application Technology, Xuzhou Medical College, No.209 Tongshan Road, Xuzhou, Jiangsu, 221004, China.
authors.forename: Yuan-Yuan
authors.initials: YY
authors.lastname: Gao
authors.affiliation: Jiangsu Province Key Laboratory of Anesthesiology, Xuzhou Medical College, Xuzhou, Jiangsu, 221004, China.|Jiangsu Province Key Laboratory of Anesthesia and Analgesia Application Technology, Xuzhou Medical College, No.209 Tongshan Road, Xuzhou, Jiangsu, 221004, China.
authors.forename: Xiao-Ya
authors.initials: XY
authors.lastname: Hong
authors.affiliation: Jiangsu Province Key Laboratory of Anesthesiology, Xuzhou Medical College, Xuzhou, Jiangsu, 221004, China. wanghon0490@sina.com.|Jiangsu Province Key Laboratory of Anesthesia and Analgesia Application Technology, Xuzhou Medical College, No.209 Tongshan Road, Xuzhou, Jiangsu, 221004, China. wanghon0490@sina.com.
authors.forename: Hong-Jun
authors.initials: HJ
authors.lastname: Wang
mesh_terms: D000700:Analgesics / Q000494:pharmacology* / Q000627:therapeutic use; D000818:Animals; D015815:Cell Adhesion Molecules / Q000235:genetics / Q000378:metabolism*; D051100:Glial Cell Line-Derived Neurotrophic Factor / Q000494:pharmacology* / Q000627:therapeutic use; D008297:Male; D000075983:Nectins; D009437:Neuralgia / Q000188:drug therapy / Q000209:etiology / Q000378:metabolism*; D059348:Peripheral Nerve Injuries / Q000150:complications / Q000378:metabolism*; D051381:Rats; D017207:Rats, Sprague-Dawley; D012584:Sciatic Nerve / Q000187:drug effects / Q000293:injuries / Q000378:metabolism*; D015398:Signal Transduction; D019061:src-Family Kinases / Q000378:metabolism
chemical_list: D000700:Analgesics; D015815:Cell Adhesion Molecules; D051100:Glial Cell Line-Derived Neurotrophic Factor; D000075983:Nectins; D019061:src-Family Kinases
keywords: C-Src; Chronic constrictive injury; Glial cell-derived neurotrophic factor (GDNF); Nectin-1; Neuropathic pain