title: Glial cell-derived neurotrophic factor attenuates neuropathic pain in a mouse model of chronic constriction injury: possible involvement of E-cadherin/p120ctn signaling.
abstract: Treating neuropathic pain is a major clinical challenge, and several key molecules associated with nociception have been suggested as potential targets for novel analgesics. Many studies have reported the anti-nociceptive effects of glial cell-derived neurotrophic factor (GDNF), but the underlying mechanism remains largely unknown. The present study was performed to assess the effects of GDNF in a mouse model of chronic constriction injury (CCI)-induced neuropathic pain. We also determined the potential role of E-cadherin/p120 catenin (p120ctn) signaling in these effects. Mice received an intrathecal acute injection of PBS, GDNF, and DECMA-1 (an E-cadherin functional blocking antibody) or a combination of DECMA-1 with GDNF on the testing days. Our results demonstrated that CCI caused a rapid decrease in E-cadherin and membrane-associated p120ctn in the spinal dorsal horn. Together, these data demonstrated that E-cadherin-associated p120ctn was upregulated by GDNF and that this upregulation was inhibited by pre-treatment with DECMA-1. Moreover, DECMA-1 significantly inhibited the effect of GDNF on thermal hyperalgesia. These data suggest that GDNF might have a therapeutic potential for the treatment of CCI-induced neuropathic pain and that the E-cadherin/p120ctn might play a role in GDNF-induced attenuation of thermal hyperalgesia.
authors.affiliation: Jiangsu Province Key Laboratory of Anesthesiology, Xuzhou Medical College, Xuzhou, Jiangsu, 221004, China.
authors.forename: Cunjin
authors.initials: C
authors.lastname: Wang
authors.forename: Hongjun
authors.initials: H
authors.lastname: Wang
authors.forename: Jun
authors.initials: J
authors.lastname: Pang
authors.forename: Li
authors.initials: L
authors.lastname: Li
authors.forename: Suming
authors.initials: S
authors.lastname: Zhang
authors.forename: Ge
authors.initials: G
authors.lastname: Song
authors.forename: Na
authors.initials: N
authors.lastname: Li
authors.forename: Junping
authors.initials: J
authors.lastname: Cao
authors.forename: Licai
authors.initials: L
authors.lastname: Zhang
mesh_terms: D000818:Animals; D015820:Cadherins / Q000235:genetics / Q000378:metabolism*; D051177:Catenins / Q000235:genetics / Q000378:metabolism*; D051100:Glial Cell Line-Derived Neurotrophic Factor / Q000235:genetics / Q000378:metabolism*; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D009437:Neuralgia / Q000209:etiology / Q000378:metabolism*; D012584:Sciatic Nerve / Q000293:injuries; D015398:Signal Transduction; D066148:Spinal Cord Dorsal Horn / Q000378:metabolism / Q000503:physiopathology; D015854:Up-Regulation; D000095002:Delta Catenin
chemical_list: D015820:Cadherins; D051177:Catenins; D051100:Glial Cell Line-Derived Neurotrophic Factor; D000095002:Delta Catenin; C000722349:Ctnnd1 protein, mouse