PDF(Pubmed)
Abstract：
Activated G-protein-coupled receptor 39 (GPR39) has been shown to attenuate inflammation by interacting with sirtuin 1 (SIRT1) and peroxisome proliferator-activated receptor-γ coactivator 1α (PGC-1α). However, whether GPR39 attenuates neuropathic pain remains unclear. In this study, we established a Sprague-Dawley rat model of spared nerve injury-induced neuropathic pain and found that GPR39 expression was significantly decreased in neurons and microglia in the spinal dorsal horn compared with sham-operated rats. Intrathecal injection of TC-G 1008, a specific agonist of GPR39, significantly alleviated mechanical allodynia in the rats with spared nerve injury, improved spinal cord mitochondrial biogenesis, and alleviated neuroinflammation. These changes were abolished by GPR39 small interfering RNA (siRNA), Ex-527 (SIRT1 inhibitor), and PGC-1α siRNA. Taken together, these findings show that GPR39 activation ameliorates mechanical allodynia by activating the SIRT1/PGC-1α pathway in rats with spared nerve injury.
摘要：
已显示激活的G蛋白偶联受体39（GPR39）通过与沉默调节蛋白1（SIRT1）和过氧化物酶体增殖物激活受体-γ共激活因子1α（PGC-1α）相互作用来减轻炎症。然而,GPR39是否减轻神经性疼痛尚不清楚.在这项研究中,我们建立了Sprague-Dawley大鼠幸免神经损伤诱导的神经病理性疼痛模型,发现与假手术大鼠相比,脊髓背角神经元和小胶质细胞中GPR39的表达显著降低.鞘内注射GPR39的特异性激动剂TC-G1008可明显减轻保留神经损伤大鼠的机械性异常疼痛。改善脊髓线粒体生物发生，减轻神经炎症.这些变化被GPR39小干扰RNA（siRNA）消除，Ex-527(SIRT1抑制剂),和PGC-1αsiRNA。一起来看,这些发现表明，GPR39激活通过激活SIRT1/PGC-1α通路改善了保留神经损伤大鼠的机械性异常疼痛。
