title: Intrathecal siRNA against GPNMB attenuates nociception in a rat model of neuropathic pain.
abstract: Neuropathic pain is characterized by hyperalgesia, allodynia, and spontaneous pain. Recent studies have shown that glycoprotein nonmetastatic melanoma B (GPNMB) plays a pivotal role in neuronal survival and neuroprotection. However, the role of GPNMB in neuropathic pain remains unknown. The aim of the present study was to assess the role of GPNMB in neuropathic pain. In cultured spinal cord neurons, we used two small interfering RNAs (siRNAs) targeting the complementary DNA (cDNA) sequence of rat GPNMB that had potent inhibitory effects on GPNMB, and siRNA1-GPNMB was selected for further in vivo study as it had the higher inhibitory effect. After sciatic nerve injury in rats, the endogenous level of GPNMB was increased in a time-dependent manner in the spinal cord. Furthermore, the intrathecal injection of siRNA1-GPNMB inhibited the expression of GPNMB and pro-inflammatory factors (TNF-α, IL-1β, and IL-6) and alleviated mechanical allodynia and thermal hyperalgesia in the chronic constriction injury (CCI) model of rats. Taken together, our findings suggest that siRNA against GPNMB can alleviate the chronic neuropathic pain caused by CCI, and this effect may be mediated by attenuated expression of TNF-α, IL-1β, and IL-6 in the spinal cord of CCI rats. Therefore, inhibition of GPNMB may provide a novel strategy for the treatment of neuropathic pain.
authors.affiliation: Department of Anesthesiology, Xiangya Hospital of Central South University, 87 Xiangya Road, Changsha, 410008, Hunan, People's Republic of China.
authors.forename: Lili
authors.initials: L
authors.lastname: Hou
authors.forename: Yanfeng
authors.initials: Y
authors.lastname: Zhang
authors.forename: Yong
authors.initials: Y
authors.lastname: Yang
authors.forename: Kai
authors.initials: K
authors.lastname: Xiang
authors.forename: Qindong
authors.initials: Q
authors.lastname: Tan
authors.forename: Qulian
authors.initials: Q
authors.lastname: Guo
mesh_terms: D000818:Animals; D015316:Genetic Therapy; D007278:Injections, Spinal; D053583:Interleukin-1beta / Q000235:genetics / Q000378:metabolism; D015850:Interleukin-6 / Q000235:genetics / Q000378:metabolism; D008297:Male; D008562:Membrane Glycoproteins / Q000235:genetics* / Q000378:metabolism; D009437:Neuralgia / Q000235:genetics / Q000378:metabolism* / Q000628:therapy; D059225:Nociception; D034741:RNA, Small Interfering / Q000235:genetics*; D051381:Rats; D017207:Rats, Sprague-Dawley; D013116:Spinal Cord / Q000378:metabolism / Q000503:physiopathology; D014409:Tumor Necrosis Factor-alpha / Q000235:genetics / Q000378:metabolism
chemical_list: C503043:Gpnmb protein, rat; D053583:Interleukin-1beta; D015850:Interleukin-6; D008562:Membrane Glycoproteins; D034741:RNA, Small Interfering; D014409:Tumor Necrosis Factor-alpha