Prior voluntary wheel running attenuates neuropathic pain.
Prior voluntary wheel running attenuates neuropathic pain.
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DOI：
10.1097/j.pain.0000000000000607
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发表时间：
2016-09
期刊：
影响因子：
7.4
通讯作者：
Watkins LR
中科院分区：
文献类型：
--
作者：
Grace PM;Fabisiak TJ;Green-Fulgham SM;Anderson ND;Strand KA;Kwilasz AJ;Galer EL;Walker FR;Greenwood BN;Maier SF;Fleshner M;Watkins LR
众所周知，运动可以产生全身性抗炎作用，但其作用是否足以防止随后的神经性疼痛尚不清楚。我们报告，在慢性压迫性损伤（CCI）前终止6周的自愿轮跑，可防止损伤持续3个月的异常性疼痛的全面发展。在CCI后3天和14天评估神经免疫信号。先前的运动使同侧脊髓背侧神经兴奋性白细胞介素（IL）-1b的表达和伴随的谷氨酸转运蛋白GLT-1的减少以及去抑制性P2 X4 R-BDNF轴的表达正常化。巨噬细胞标志物Iba 1和趋化因子CCL 2（MCP-1），和神经元损伤标志物（激活转录因子3）的表达，衰减之前运行在同侧腰背根神经节。先前的运动抑制了巨噬细胞浸润和/或损伤部位增殖，因为巨噬细胞标志物Iba 1、iNOS（M1）和Arg-1（M2;表达呈时间依赖性）的存在减少。慢性缩窄性损伤驱动的血清促炎趋化因子的增加被先前的跑步抑制，而IL-10增加。外周血单核细胞也刺激脂多糖离体，其中CCI诱导的IL-1b，亚硝酸盐，和IL-10的增加被抑制先前的运动。最后，不受限制的自愿轮运行，无论是当天开始，或2周后，CCI，逐步扭转神经性疼痛。这项研究是第一个调查的行为和神经免疫的后果，定期运动终止前神经损伤。这项研究表明，慢性疼痛应该被认为是“身体不活动的疾病体”的一个组成部分，积极的生活方式可以预防神经性疼痛。
Exercise is known to exert a systemic anti-inflammatory influence, but whether its effects are sufficient to protect against subsequent neuropathic pain is underinvestigated. We report that 6 weeks of voluntary wheel running terminating before chronic constriction injury (CCI) prevented the full development of allodynia for the; 3-month duration of the injury. Neuroimmune signaling was assessed at 3 and 14 days after CCI. Prior exercise normalized ipsilateral dorsal spinal cord expression of neuroexcitatory interleukin (IL)-1b production and the attendant glutamate transporter GLT-1 decrease, as well as expression of the disinhibitory P2X4R-BDNF axis. The expression of the macrophage marker Iba1 and the chemokine CCL2 (MCP-1), and a neuronal injury marker (activating transcription factor 3), was attenuated by prior running in the ipsilateral lumbar dorsal root ganglia. Prior exercise suppressed macrophage infiltration and/or injury site proliferation, given decreased presence of macrophage markers Iba1, iNOS (M1), and Arg-1 (M2; expression was time dependent). Chronic constriction injury–driven increases in serum proinflammatory chemokines were suppressed by prior running, whereas IL-10 was increased. Peripheral blood mononuclear cells were also stimulated with lipopolysaccharide ex vivo, wherein CCI-induced increases in IL-1b, nitrite, and IL-10 were suppressed by prior exercise. Last, unrestricted voluntary wheel running, beginning either the day of, or 2 weeks after, CCI, progressively reversed neuropathic pain. This study is the first to investigate the behavioral and neuroimmune consequences of regular exercise terminating before nerve injury. This study suggests that chronic pain should be considered a component of “the diseasome of physical inactivity,” and that an active lifestyle may prevent neuropathic pain.