Eastman Institute for Oral Health, University of Rochester, Rochester, NY, USA.
Eastman Institute for Oral Health, University of Rochester, Rochester, NY, USA.
Cytokine. 2021 Jul;143:155540. doi: 10.1016/j.cyto.2021.155540. Epub 2021 Apr 24.
Pain may undergo modulation in the central nervous system prior to reaching the primary somatosensory cortex and being perceived as pain. Faulty pain modulation mechanisms have been linked to various chronic pain conditions. Cytokines such as IL-10 and IL-1beta, are known to be involved in initiation and maintenance of neuropathic pain. In this study, we investigated the association between pain modulation profile, pain intensity and cytokines (IL-10 and IL-1beta) levels in a rat model of neuropathic pain.
Exercise-Induced Hypoalgesia (EIH) was assessed by evaluating the percentage of responses to a train of 60g mechanical stimuli before and after 180 seconds of exercise on a rotating rod. The differences in the response rates before and after the exercise were used to divide the rats into low and high EIH responders. Rats from low and high EIH groups underwent constriction injury of the left sciatic nerve. Pain behavior (allodynia and hyperalgesia) were assessed by measuring responses to mechanical and thermal stimuli applied to the plantar surface of the foot. Serum, sciatic nerve and the related Dorsal Root Ganglia (DRG) levels of IL-10 and IL-1beta were determined by ELISA. The DRG mRNA levels of IL-10 and IL-1beta measured with PCR. A comparison between the low and high EIH rats of all measured parameters was made.
The low EIH rats developed significantly more severe allodynia and hyperalgesia in the affected paw and allodynia in the contralateral paw compared to the high EIH rats, 7 days following the injury. The low EIH rats had higher IL-1beta protein levels in serum prior to and following injury, higher affected and contralateral sciatic nerve IL-1beta levels following injury and higher IL-1beta levels in the contralateral DRG (protein and mRNA) following injury when compared to high EIH rats. The high EIH rats had higher affected sciatic nerve IL-10 levels following nerve injury and higher IL-10 levels of both protein and mRNA in the affected and contralateral DRG at baseline and following injury.
EIH profile was found to be predictive of pain behavior following nerve injury, low EIH rats developed more severe allodynia and hyperalgesia. IL-1beta may be associated with painful neuropathy developed in rats with low EIH while the anti-inflammatory cytokine IL-10 may have a protective role, inhibiting the development of painful.
疼痛在到达初级体感皮层并被感知为疼痛之前，可能在中枢神经系统中受到调节。疼痛调节机制的故障与各种慢性疼痛状况有关。白细胞介素-10 (IL-10) 和白细胞介素-1β (IL-1β) 等细胞因子已知参与神经病理性疼痛的发生和维持。在这项研究中，我们调查了神经病理性疼痛大鼠模型中疼痛调节谱、疼痛强度和细胞因子 (IL-10 和 IL-1β) 水平之间的关联。
通过评估 60g 机械刺激的反应率，在旋转棒上进行 180 秒运动前后，评估运动诱导的镇痛（EIH）。运动前后反应率的差异用于将大鼠分为低和高 EIH 反应者。来自低和高 EIH 组的大鼠接受左坐骨神经缩窄损伤。通过测量足底对机械和热刺激的反应来评估疼痛行为（痛觉过敏和痛觉过度）。通过 ELISA 测定血清、坐骨神经和相关背根神经节 (DRG) 中 IL-10 和 IL-1β 的水平。通过 PCR 测量 DRG 中 IL-10 和 IL-1β 的 mRNA 水平。对所有测量参数的低和高 EIH 大鼠进行比较。
与高 EIH 大鼠相比，低 EIH 大鼠在损伤后 7 天，受影响的爪子出现更严重的痛觉过敏和痛觉过度，对侧爪子出现痛觉过敏。低 EIH 大鼠在损伤前和损伤后血清中 IL-1β 蛋白水平较高，损伤后受影响和对侧坐骨神经 IL-1β 水平较高，对侧 DRG（蛋白和 mRNA）IL-1β 水平较高。高 EIH 大鼠在神经损伤后受影响的坐骨神经 IL-10 水平较高，在损伤前和损伤后受影响和对侧 DRG 中 IL-10 的蛋白和 mRNA 水平较高。
EIH 特征被发现可预测神经损伤后的疼痛行为，低 EIH 大鼠出现更严重的痛觉过敏和痛觉过度。IL-1β 可能与低 EIH 大鼠发生的痛性神经病有关，而抗炎细胞因子 IL-10 可能具有保护作用，抑制痛性的发展。
