Department of Anesthesiology, The Second Affiliated Hospital of Nantong University, Nantong 226001, Jiangsu, China.
ICU, The Second Affiliated Hospital of Nantong University, Nantong 226001, Jiangsu, China.
Life Sci. 2021 Jul 15;277:119489. doi: 10.1016/j.lfs.2021.119489. Epub 2021 Apr 13.
Nod-like receptor family pyrin domain containing 3 (NLRP3) may play an important role in neuropathic pain. Treatment for trigeminal neuropathic pain remains a challenge, as common drugs either do not demonstrate beneficial therapeutic effects or induce intolerance in patients.
In a rat model of trigeminal neuropathic pain, pain caused by the malpositioning of dental implants is similar to that experienced by humans. We used masculine Sprague-Dawley rats with inferior alveolar nerve damage as a model to investigate the differential regulation of NLRP3. First, we confirmed the level of NLRP3 in the medullary dorsal horn and variation of pain response behavior after silencing the expression of NLRP3 inflammasome bodies in rats with trigeminal neuropathic pain. Second, under localized anesthesia, we extracted the lower left second molar, implanted a micro-dental implant, and deliberately injured the inferior alveolar nerve.
After nerve damage, the level of NLRP3-related inflammasomes was upregulated in microglia and the expression of a component of the inflammasome gradually increased during postoperative days 3-21. The suppression of adenovirus-shRNA-NLRP3 on postoperative day 1 markedly inhibited the expression of pro-inflammatory cytokines and the activation of the inflammasome and mechanical allodynia. Furthermore, it attenuated cell death in microglia, as evidenced by increased Bcl-2, Bcl-xL, Bax, and Bik expression.
The level of NLRP3 in the dorsal horn is a pivotal factor in trigeminal neuropathic pain, and inhibition of the early expression of NLRP3 might serve as a potential therapeutic approach.
核苷酸结合寡聚化结构域样受体家族包含pyrin 结构域 3（NLRP3）可能在神经病理性疼痛中发挥重要作用。三叉神经病理性疼痛的治疗仍然是一个挑战，因为常用药物要么没有显示出有益的治疗效果，要么在患者中引起不耐受。
在牙齿植入物错位引起的三叉神经病理性疼痛大鼠模型中，疼痛类似于人类所经历的疼痛。我们使用雄性 Sprague-Dawley 大鼠，其下牙槽神经损伤作为模型来研究 NLRP3 的差异调节。首先，我们确认了 NLRP3 在背角中的水平，并在三叉神经病理性疼痛大鼠中沉默 NLRP3 炎性小体后，观察疼痛反应行为的变化。其次，在局部麻醉下，我们提取左下第二磨牙，植入微型牙种植体，并故意损伤下牙槽神经。
神经损伤后，小神经胶质细胞中 NLRP3 相关炎性小体的水平上调，并且炎性小体的一个组成部分的表达在术后第 3-21 天逐渐增加。术后第 1 天，腺病毒-shRNA-NLRP3 的抑制显著抑制了促炎细胞因子的表达和炎性小体的激活以及机械性感觉过敏。此外，它通过增加 Bcl-2、Bcl-xL、Bax 和 Bik 的表达来减轻小神经胶质细胞的死亡。
背角中 NLRP3 的水平是三叉神经病理性疼痛的关键因素，抑制 NLRP3 的早期表达可能是一种潜在的治疗方法。
