Wang Dongmei, Xue Yaping, Chen Yajuan, Ruan Liqin, Hong Yanguo
College of Life Sciences and Provincial Key Laboratory of Developmental Biology and Neuroscience, Fujian Normal University Fuzhou, Fujian 350108, People's Republic of China.
College of Life Sciences and Provincial Key Laboratory of Developmental Biology and Neuroscience, Fujian Normal University Fuzhou, Fujian 350108, People's Republic of China.
Neurosci Lett. 2016 Apr 8;618:115-121. doi: 10.1016/j.neulet.2016.03.004. Epub 2016 Mar 4.
Mas-related gene (Mrg) C receptors are exclusively expressed in the trigeminal and dorsal root ganglia (DRG). However, their functional roles are poorly understood. This study was aimed to determine the effect of MrgC receptors on pain hypersensitivity in the early phase of neuropathic pain and its underlying mechanisms. Intrathecal (i.t.) administration of the selective MrgC receptor agonist bovine adrenal medulla 8-22 (BAM8-22) at 1 or 10nmol attenuated mechanical allodynia one day after L5 spinal nerve ligation (SNL) surgery. I.t. BAM8-22 (10 nmol) inhibited SNL-induced microglia activation in the spinal dorsal horn on day 2 post-SNL. The BAM8-22 treatment also abolished SNL-induced upregulation of neuronal nitric oxide synthesis (nNOS) in the dorsal root ganglia (DRG). On the other hand, SNL, but not sham, surgery reduced the expression of MrgC receptor mRNA in the injured L5 DRG without changing thier levels in the adjacent uninjured L4 or L6 DRG on day 2 following the surgery. These results suggest that the activation of MrgC receptors can relieve pain hypersensitivity by the inhibition of nNOS increase in DRG neurons and microglia activation in the spinal dorsal horn in the early time following peripheral nerve injury. This study provides evidence that MrgC receptors could be targeted as a novel therapy for neuropathic pain with limited unwanted effects.
Mas相关基因（Mrg）C受体仅在三叉神经节和背根神经节（DRG）中表达。然而，它们的功能作用尚不清楚。本研究旨在确定MrgC受体在神经性疼痛早期对疼痛超敏反应的影响及其潜在机制。在L5脊神经结扎（SNL）手术后一天，鞘内（i.t.）注射1或10 nmol的选择性MrgC受体激动剂牛肾上腺髓质8-22（BAM8-22）可减轻机械性异常性疼痛。i.t.注射BAM8-22（10 nmol）可在SNL后第2天抑制脊髓背角中SNL诱导的小胶质细胞激活。BAM8-22治疗还消除了SNL诱导的背根神经节（DRG）中神经元型一氧化氮合酶（nNOS）的上调。另一方面，SNL手术（而非假手术）在术后第2天降低了损伤的L5 DRG中MrgC受体mRNA的表达，而未改变相邻未损伤的L4或L6 DRG中的水平。这些结果表明，在周围神经损伤后的早期，MrgC受体的激活可通过抑制DRG神经元中nNOS的增加和脊髓背角中小胶质细胞的激活来缓解疼痛超敏反应。本研究提供了证据表明，MrgC受体可作为一种副作用有限的新型神经性疼痛治疗靶点。
