Journal of Molecular Neuroscience

, Volume 55, Issue 2, pp 533–540 | Cite as

Intrathecal siRNA Against GPNMB Attenuates Nociception in a Rat Model of Neuropathic Pain

  • Lili Hou
  • Yanfeng Zhang
  • Yong Yang
  • Kai Xiang
  • Qindong Tan
  • Qulian Guo
Article

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.

Keywords

GPNMB RNA interference Neuropathic pain 

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Copyright information

© Springer Science+Business Media New York 2014

Authors and Affiliations

  • Lili Hou
    • 1
  • Yanfeng Zhang
    • 1
  • Yong Yang
    • 1
  • Kai Xiang
    • 1
  • Qindong Tan
    • 2
  • Qulian Guo
    • 1
  1. 1.Department of AnesthesiologyXiangya Hospital of Central South UniversityChangshaPeople’s Republic of China
  2. 2.Department of AnesthesiologyThe Third Affiliated Hospital of Nanfang Medicine UniversityGuangzhouPeople’s Republic of China

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