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

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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.

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Authors and Affiliations

  1. Department of Anesthesiology, Xiangya Hospital of Central South University, 87 Xiangya Road, Changsha, 410008, Hunan, People’s Republic of China

    Lili Hou, Yanfeng Zhang, Yong Yang, Kai Xiang & Qulian Guo

  2. Department of Anesthesiology, The Third Affiliated Hospital of Nanfang Medicine University, Guangzhou, 510063, Guangdong, People’s Republic of China

    Qindong Tan

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  1. Lili Hou
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  2. Yanfeng Zhang
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  3. Yong Yang
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  4. Kai Xiang
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  5. Qindong Tan
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  6. Qulian Guo
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Correspondence to Qulian Guo.

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Hou, L., Zhang, Y., Yang, Y. et al. Intrathecal siRNA Against GPNMB Attenuates Nociception in a Rat Model of Neuropathic Pain. J Mol Neurosci 55, 533–540 (2015). https://doi.org/10.1007/s12031-014-0379-3

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  • DOI: https://doi.org/10.1007/s12031-014-0379-3

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