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rTMS 诱导神经病理性疼痛模型大鼠镇痛,并调节神经炎症和神经可塑性。

rTMS induces analgesia and modulates neuroinflammation and neuroplasticity in neuropathic pain model rats.

机构信息

Programa de Pós-Graduação em Ciências Biológicas: Farmacologia e Terapêutica - Instituto de Ciências Básicas da Saúde - Universidade Federal do Rio Grande do Sul (UFRGS), Porto Alegre, RS, Brazil; Laboratório de Farmacologia da Dor e Neuromodulação: Investigações Pré-clínicas - Hospital de Clínicas de Porto Alegre, Porto Alegre, RS, Brazil.

Laboratório de Farmacologia da Dor e Neuromodulação: Investigações Pré-clínicas - Hospital de Clínicas de Porto Alegre, Porto Alegre, RS, Brazil; Programa de Pós-Graduação em Medicina: Ciências Médicas - Universidade Federal do Rio Grande do Sul, Porto Alegre, RS, Brazil.

出版信息

Brain Res. 2021 Jul 1;1762:147427. doi: 10.1016/j.brainres.2021.147427. Epub 2021 Mar 15.

DOI:10.1016/j.brainres.2021.147427
PMID:33737061
Abstract

Neuropathic pain (NP) is related to the presence of hyperalgesia, allodynia, and spontaneous pain, affecting 7%-10% of the general population. Repetitive transcranial magnetic stimulation (rTMS) is applied for NP relief, especially in patients with refractory pain. As NP response to existing treatments is often insufficient, we aimed to evaluate rTMS treatment on the nociceptive response of rats submitted to an NP model and its effect on pro-and anti-neuroinflammatory cytokine and neurotrophin levels. A total of 106 adult male Wistar rats (60 days old) were divided into nine experimental groups: control, control + sham rTMS, control + rTMS, sham NP, sham neuropathic pain + sham rTMS, sham neuropathic pain + rTMS, NP, neuropathic pain + sham rTMS, and neuropathic pain + rTMS. NP establishment was achieved 14 days after the surgery to establish chronic constriction injury (CCI) of the sciatic nerve. Rats were treated with 5 min daily sessions of rTMS for eight consecutive days. Nociceptive behavior was assessed using von Frey and hot plate tests at baseline, after NP establishment, and post-treatment. Biochemical assays to assess the levels of brain-derived neurotrophic factor (BDNF), tumor necrosis factor-alpha (TNF-α), and interleukin (IL)-10, were performed in the prefrontal cortex (PFC) and spinal cord tissue homogenates. rTMS treatment promoted a partial reversal of mechanical allodynia and total reversal of thermal hyperalgesia induced by CCI. Moreover, rTMS increased the levels of BDNF, TNF-α, and IL-10 in the PFC. rTMS may be a promising tool for the treatment of NP. The alterations induced by rTMS on neurochemical parameters may have contributed to the analgesic effect presented.

摘要

神经病理性疼痛(NP)与痛觉过敏、感觉异常和自发性疼痛有关,影响着 7%-10%的普通人群。重复经颅磁刺激(rTMS)被应用于缓解 NP,特别是在难治性疼痛患者中。由于 NP 对现有治疗的反应往往不足,我们旨在评估 rTMS 治疗对 NP 模型大鼠伤害感受反应的影响及其对促炎和抗炎细胞因子及神经营养因子水平的影响。共有 106 只成年雄性 Wistar 大鼠(60 天龄)分为九个实验组:对照组、对照组+假 rTMS 组、对照组+rTMS 组、假 NP 组、假 NP+假 rTMS 组、假 NP+rTMS 组、NP 组、NP+假 rTMS 组和 NP+rTMS 组。NP 的建立是在手术建立慢性坐骨神经缩窄性损伤(CCI)后的第 14 天完成的。大鼠每天接受 5 分钟的 rTMS 治疗,连续 8 天。使用 von Frey 和热板试验在基线、NP 建立后和治疗后评估痛觉行为。在额前皮质(PFC)和脊髓组织匀浆中进行生物化学测定,以评估脑源性神经营养因子(BDNF)、肿瘤坏死因子-α(TNF-α)和白细胞介素(IL)-10 的水平。rTMS 治疗促进了 CCI 引起的机械性痛觉过敏的部分逆转和热痛觉过敏的完全逆转。此外,rTMS 增加了 PFC 中 BDNF、TNF-α 和 IL-10 的水平。rTMS 可能是治疗 NP 的一种有前途的工具。rTMS 对神经化学参数的改变可能有助于其呈现出的镇痛效果。

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