The Role of NLRP1 Inflammasome and Interleukin 1β in Experimental Neuropathic Pain Model in Rat and the Effect of Tramadol Treatment.

Tuba Tanyel Saracoglu, Cigdem Cengelli Unel, Nusin Harmanci, Engin Yildirim, Ayten Bilir, Sacit Gulec
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Abstract

Aim: To evaluate the effects of tramadol on inflammation by measuring NLRP1 and IL-1 beta (IL-1β) levels in an experimental neuropathic pain model.

Material and methods: Sprague-Dawley rats were divided into three groups: control, chronic constriction injury (CCI), and CCI + tramadol. Neuropathic pain was assessed using mechanical allodynia, thermal hyperalgesia, and cold allodynia. IL-1β and NLRP1 levels were evaluated using ELISA on sciatic nerve (SN), dorsal root ganglion (DRG), and serum either on day 3 or days 8 postsurgery.

Results: On day 3, paw withdrawal latency (PWL) was lower in the CCI and CCI + tramadol groups than the control group in both mechanical and cold allodynia tests. On day 8, the PWL in the CCI group was also lower than in the control group. In contrast, tramadol increased the PWL on day 8 compared to day 3 in the CCI group. During cold allodynia, PWL decreased in the CCI group, however, tramadol reversed this effect on days 3 and 8. Tramadol, therefore, ameliorated pain hypersensitivity in mechanical/cold allodynia tests. Serum IL-1β levels were higher in the CCI + tramadol and CCI groups than the control group, although serum IL-1β levels in the CCI and CCI + tramadol groups were comparable. Tramadol decreased the IL-1β and NLRP1 in DRG compared with the CCI group. A similar trend was observed in the SN samples.

Conclusion: Our experiments revealed an increase in IL-1β and NLRP-1 levels in a neuropathic pain model and found that tramadol had an anti-inflammatory effect on the IL-1β and NLRP1 inflammasomes.

NLRP1炎症体和白细胞介素1β在大鼠实验性神经病理性疼痛模型中的作用及曲马多治疗的效果
目的:神经性疼痛可由糖尿病、神经损伤、带状疱疹后遗神经痛、多发性硬化症和脊髓损伤引起,起源于周围神经系统或中枢神经系统。多种炎症介质在神经病理性疼痛的发病机制中发挥作用。在本研究中,我们通过测量实验性神经病理性疼痛模型中的 NLRP1 和 IL-1 beta(IL-1β)水平,评估了曲马多对炎症的影响:将 Sprague-Dawley 大鼠分为三组:对照组、慢性收缩性损伤(CCI)组和 CCI + 曲马多组。用机械痛觉、热痛觉和冷痛觉评估神经病理性疼痛。在手术后第3天或第8天,使用ELISA法对坐骨神经(SN)、背根神经节(DRG)和血清中的IL-1β和NLRP1水平进行评估:第3天,CCI组和CCI+曲马多组在机械痛和冷觉过敏试验中的爪退缩潜伏期(PWL)均低于对照组。第8天,CCI组的PWL也低于对照组。相反,与第3天相比,曲马多在第8天增加了CCI组的脉搏波速度。在冷异感期间,CCI 组的脉搏波速度降低,但曲马多在第 3 天和第 8 天逆转了这种效应。因此,曲马多可改善机械/冷异感试验中的痛觉过敏性。CCI+曲马多组和CCI组的血清IL-1β水平高于对照组,但CCI组和CCI+曲马多组的血清IL-1β水平相当。与CCI组相比,曲马多降低了DRG中的IL-1β和NLRP1。在SN样本中也观察到了类似的趋势:我们的实验显示神经病理性疼痛模型中IL-1β和NLRP-1水平升高,并发现曲马多对IL-1β和NLRP1炎性体具有抗炎作用。
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