Interleukin-4 mediates the analgesia produced by low-intensity exercise in mice with neuropathic pain.
Interleukin-4 mediates the analgesia produced by low-intensity exercise in mice with neuropathic pain.
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DOI：
10.1097/j.pain.0000000000001109
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发表时间：
2018-03
期刊：
影响因子：
7.4
通讯作者：
Santos ARS
中科院分区：
文献类型：
--
作者：
Bobinski F;Teixeira JM;Sluka KA;Santos ARS
周围神经损伤（PNI）激活免疫系统，导致损伤部位和脊髓背角的促炎细胞因子增加。运动调节免疫系统，促进未受伤肌肉中巨噬细胞的抗炎表型，并且抗炎细胞因子的增加可以促进愈合和镇痛。我们认为PNI会减少损伤部位和脊髓中抗炎细胞因子的释放，而跑步机运动会增加。我们发现两周的跑步机运动改善了小鼠的神经性疼痛行为：机械性痛觉过敏、逃避/回避行为和自发运动活动。PNI降低神经损伤部位和脊髓背角的抗炎细胞因子（IL-4、IL-1 ra、IL-5），而运动使IL-4、IL-1 ra、IL-5浓度恢复至损伤前水平。IL-4-/-小鼠和用IL-4抗体处理的小鼠没有对跑步机运动产生镇痛作用。使用坐骨神经的免疫组织化学染色，与久坐小鼠相比，跑步机运动增加了M2-巨噬细胞（分泌抗炎细胞因子）的百分比，并减少了M1-巨噬细胞（分泌促炎细胞因子）。运动小鼠中M2巨噬细胞的增加和M1巨噬细胞的减少在IL-4−/−小鼠中没有发生。在脊髓中，PNI增加胶质细胞活化，BDNF和β-NGF水平，降低IL-4和IL-1 ra水平，而跑台运动抑制胶质细胞活化（GFAP和Iba 1免疫反应性），降低BDNF和β-NGF，增加IL-4，IL-1 ra，IL-5。我们的研究结果表明，IL-4介导的低强度运动产生的镇痛通过调节外周和中枢神经免疫反应在神经病理性疼痛小鼠。
Peripheral nerve injury (PNI) activates the immune system resulting in increased pro-inflammatory cytokines at the site of injury and in the spinal cord dorsal horn. Exercise modulates the immune system promoting an anti-inflammatory phenotype of macrophages in uninjured muscle, and increases in anti-inflammatory cytokines can promote healing and analgesia. We proposed that PNI will decrease, and treadmill exercise will increase, release of anti-inflammatory cytokines at the site of injury and in the spinal cord. We show two weeks of treadmill exercise improves neuropathic pain behaviors in mice: mechanical hyperalgesia, escape/avoidance behavior, and spontaneous locomotor activity. PNI reduced anti-inflammatory cytokines (IL-4, IL-1ra, IL-5) at the site of nerve injury and in the spinal dorsal horn while exercise restored IL-4, IL-1ra, IL-5 concentrations to pre-injury levels. IL4−/− mice, and mice treated with IL-4 antibody did not develop analgesia to treadmill exercise. Using immunohistochemical staining of the sciatic nerve, treadmill exercise increased the percentage of M2-macrophages (secretes anti-inflammatory cytokines), and decreased M1-macrophages (secretes pro-inflammatory cytokines) when compared to sedentary mice. The increased M2 and decreased M1 macrophages in exercised mice did not occur in IL-4−/− mice. In the spinal cord, PNI increased glial cell activation, BDNF and β-NGF levels, and decreased IL-4 and IL-1ra levels while treadmill exercise suppressed glial cells activation (GFAP and Iba1 immunoreactivity), reduced BDNF and β-NGF, and increased IL-4, IL-1ra, IL-5. Our results suggest IL-4 mediates the analgesia produced by low-intensity exercise by modulating peripheral and central neuroimmune responses in mice with neuropathic pain.
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DOI：
10.1016/j.berh.2015.04.022
发表时间：
2015-02
期刊：
Best practice & research. Clinical rheumatology
影响因子：
--
作者：
Ambrose KR;Golightly YM
通讯作者：
Golightly YM
影响因子：
3.3
作者：
Bobinski, F.;Martins, D. F.;Santos, A. R. S.
通讯作者：
Santos, A. R. S.
影响因子：
7.3
作者：
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通讯作者：
Ferreira, SH
影响因子：
5.7
作者：
Chen, Yu-Wen;Li, Yung-Tsung;Hung, Ching-Hsia
通讯作者：
Hung, Ching-Hsia
影响因子：
5.3
作者：
Dobson JL;McMillan J;Li L
通讯作者：
Li L