Kida Kotaro, Marutani Eizo, Nguyen Rebecca K, Ichinose Fumito
Department of Anesthesia, Critical Care and Pain Medicine, Massachusetts General Hospital and Harvard Medical School, Boston, MA, USA.
Department of Anesthesia, Critical Care and Pain Medicine, Massachusetts General Hospital and Harvard Medical School, Boston, MA, USA.
Nitric Oxide. 2015 Apr 30;46:87-92. doi: 10.1016/j.niox.2014.11.014. Epub 2014 Nov 24.
Increasing evidence suggests that the pathogenesis of neuropathic pain is mediated through activation of microglia in the spinal cord. Hydrogen sulfide attenuates microglial activation and central nervous system inflammation; however, the role of hydrogen sulfide in neuropathic pain is unclear. In this study, we examined the effects of hydrogen sulfide breathing on neuropathic pain in mice. C57BL/6J mice were subjected to chronic constriction injury (CCI) of the sciatic nerve. After CCI, mice breathed air alone or air mixed with hydrogen sulfide at 40 ppm for 8 h on 7 consecutive days. The expression levels of inflammatory cytokines including interleukin 6 (IL-6) were measured in the spinal cord. Effects of hydrogen sulfide on IL-6-induced activation of microglia were examined in primary rat microglia. Mice that breathed air alone exhibited the neuropathic pain behavior including mechanical allodynia and thermal hyperalgesia and increased mRNA levels of IL-6 and chemokine CC motif ligand 2 (CCL2) after CCI. Inhaled hydrogen sulfide prevented the neuropathic pain behavior and attenuated the upregulation of inflammatory cytokines. Sodium sulfide inhibited IL-6-induced activation of primary microglia. These results suggest that inhaled hydrogen sulfide prevents the development of neuropathic pain in mice possibly via inhibition of the activation of microglia in the spinal cord.
越来越多的证据表明，神经性疼痛的发病机制是通过脊髓中小胶质细胞的激活介导的。硫化氢可减弱小胶质细胞的激活和中枢神经系统炎症；然而，硫化氢在神经性疼痛中的作用尚不清楚。在本研究中，我们研究了吸入硫化氢对小鼠神经性疼痛的影响。将C57BL/6J小鼠坐骨神经进行慢性缩窄损伤（CCI）。CCI后，小鼠连续7天每天单独呼吸空气或呼吸含40 ppm硫化氢的混合空气8小时。检测脊髓中包括白细胞介素6（IL-6）在内的炎性细胞因子的表达水平。在原代大鼠小胶质细胞中检测硫化氢对IL-6诱导的小胶质细胞激活的影响。单独呼吸空气的小鼠在CCI后表现出神经性疼痛行为，包括机械性异常性疼痛和热痛觉过敏，且IL-6和趋化因子CC基序配体2（CCL2）的mRNA水平升高。吸入硫化氢可预防神经性疼痛行为，并减弱炎性细胞因子的上调。硫化钠抑制IL-6诱导的原代小胶质细胞激活。这些结果表明，吸入硫化氢可能通过抑制脊髓中小胶质细胞的激活来预防小鼠神经性疼痛的发展。
