Analgesic Effect of Exercise on Neuropathic Pain via Regulating the Complement Component 3 of Reactive Astrocytes.

IF 4.6 2区 医学 Q1 ANESTHESIOLOGY Anesthesia and analgesia Pub Date : 2024-10-01 Epub Date: 2024-01-31 DOI:10.1213/ANE.0000000000006884
Chenghao Wang, Hui He, Tianchi Gao, Xinzheng Sun, Lixia Du, Yayue Yang, Jianyu Zhu, Yachen Yang, Yanqing Wang, Wenli Mi
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Abstract

Background: Exercise has been proven to be an efficient intervention in attenuating neuropathic pain. However, the underlying mechanisms that drive exercise analgesia remain unknown. In this study, we aimed to examine the role of complement component 3 (C3) in neuropathic pain and whether antinociceptive effects are produced by exercise via regulating C3 in mice.

Methods: In this study, using a spared nerve injury (SNI)-induced neuropathic pain mice model, C57BL/6J mice were divided into 3 groups: Sham mice, SNI mice, and SNI + Exercise (Ex) mice with 30-minute low-intensity aerobic treadmill running (10 m/min, no inclination). Paw withdrawal threshold; thermal withdrawal latency; and glial fibrillary acidic protein, C3, tumor necrosis factor-α, and interlukin-1β expression in the spinal cord were monitored. C3 knockout (KO) mice were further used to verify the role of C3 in neuropathic pain.

Results: von Frey test, acetone test, and CatWalk gait analysis revealed that treadmill exercise for 4 weeks reversed pain behaviors. In addition, exercise reduced astrocyte reactivity (SNI mean = 14.5, 95% confidence interval [CI], 12.7-16.3; SNI + Ex mean = 10.3, 95% CI, 8.77-11.9, P = .0003 SNI + Ex versus SNI) and inflammatory responses in the spinal cord after SNI. Moreover, it suppressed the SNI-induced upregulation of C3 expression in the spinal cord (SNI mean = 5.46, 95% CI, 3.39-7.53; SNI + Ex mean = 2.41, 95% CI, 1.42-3.41, P = .0054 SNI + Ex versus SNI in Western blot). C3 deficiency reduced SNI-induced pain and spinal astrocyte reactivity (wild type mean = 7.96, 95% CI, 6.80-9.13; C3 KO mean = 5.98, 95% CI, 5.14-6.82, P = .0052 C3 KO versus wild type). Intrathecal injection of recombinant C3 (rC3) was sufficient to produce mechanical (rC3-Ex mean = 0.77, 95% CI, 0.15-1.39; rC3 mean = 0.18, 95% CI, -0.04 to 0.41, P = .0168 rC3-Ex versus rC3) and cold (rC3-Ex mean = 1.08, 95% CI, 0.40-1.77; rC3 mean = 3.46, 95% CI, 1.45-5.47, P = .0025 rC3-Ex versus rC3) allodynia in mice. Importantly, exercise training relieved C3-induced mechanical and cold allodynia, and the analgesic effect of exercise was attenuated by a subeffective dose of intrathecal injection of C3.

Conclusions: Overall, these results suggest that exercise suppresses neuropathic pain by regulating astroglial C3 expression and function, thereby providing a rationale for the analgesic effect of exercise as an acceptable alternative approach for treating neuropathic pain.

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运动通过调节反应性星形胶质细胞的补体成分 3 对神经性疼痛有镇痛作用
背景:运动已被证明是减轻神经性疼痛的有效干预措施。然而,运动镇痛的潜在机制仍然未知。在这项研究中,我们旨在研究补体成分 3(C3)在神经病理性疼痛中的作用,以及运动是否通过调节小鼠体内的 C3 而产生镇痛效果:本研究使用神经损伤(SNI)诱导的神经病理性疼痛小鼠模型,将 C57BL/6J 小鼠分为 3 组:假小鼠、SNI 小鼠和 SNI + 运动(Ex)小鼠,进行 30 分钟低强度有氧跑步机跑步(10 米/分钟,无倾角)。监测爪退缩阈值、热退缩潜伏期以及脊髓中胶质纤维酸性蛋白、C3、肿瘤坏死因子-α和interlukin-1β的表达。结果:von Frey 试验、丙酮试验和 CatWalk 步态分析表明,连续 4 周的跑步机运动可逆转疼痛行为。此外,运动降低了星形胶质细胞的反应性(SNI 平均值 = 14.5,95% 置信区间 [CI],12.7-16.3;SNI + Ex 平均值 = 10.3,95% 置信区间 [CI],8.77-11.9,P = .0003 SNI + Ex 与 SNI 相比)和 SNI 后脊髓的炎症反应。此外,它还抑制了 SNI 诱导的脊髓中 C3 表达的上调(在 Western 印迹中,SNI 平均值 = 5.46,95% CI,3.39-7.53;SNI + Ex 平均值 = 2.41,95% CI,1.42-3.41,P = .0054 SNI + Ex 与 SNI 相比)。C3 缺乏会降低 SNI 诱导的疼痛和脊髓星形胶质细胞反应性(野生型平均值 = 7.96,95% CI,6.80-9.13;C3 KO 平均值 = 5.98,95% CI,5.14-6.82,P = .0052 C3 KO 与野生型相比)。鞘内注射重组 C3(rC3)足以产生机械效应(rC3-Ex 平均值 = 0.77,95% CI,0.15-1.39;rC3 平均值 = 0.18,95% CI,-0.04 至 0.41,P = .0168 rC3-Ex 与 rC3 相比)和小鼠冷(rC3-Ex 平均值 = 1.08,95% CI,0.40-1.77;rC3 平均值 = 3.46,95% CI,1.45-5.47,P = .0025 rC3-Ex 与 rC3 相比)过敏症。重要的是,运动训练能缓解 C3 引起的机械和冷异感症,而亚有效剂量的鞘内注射 C3 会减弱运动的镇痛效果:总之,这些结果表明,运动可通过调节星形胶质细胞 C3 的表达和功能来抑制神经性疼痛,从而为运动的镇痛作用提供了理论依据,使其成为治疗神经性疼痛的一种可接受的替代方法。
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来源期刊
Anesthesia and analgesia
Anesthesia and analgesia 医学-麻醉学
CiteScore
9.90
自引率
7.00%
发文量
817
审稿时长
2 months
期刊介绍: Anesthesia & Analgesia exists for the benefit of patients under the care of health care professionals engaged in the disciplines broadly related to anesthesiology, perioperative medicine, critical care medicine, and pain medicine. The Journal furthers the care of these patients by reporting the fundamental advances in the science of these clinical disciplines and by documenting the clinical, laboratory, and administrative advances that guide therapy. Anesthesia & Analgesia seeks a balance between definitive clinical and management investigations and outstanding basic scientific reports. The Journal welcomes original manuscripts containing rigorous design and analysis, even if unusual in their approach.
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