Kochi Takahiro, Nakamura Yoki, Ma Simeng, Hisaoka-Nakashima Kazue, Wang Dengli, Liu Keyue, Wake Hidenori, Nishibori Masahiro, Irifune Masahiro, Morioka Norimitsu
Department of Pharmacology, Graduate School of Biomedical and Health Sciences, Hiroshima University, 1-2-3 Kasumi, Minami-ku, Hiroshima 734-8553, Japan.
Department of Dental Anesthesiology, Graduate School of Biomedical and Health Sciences, Hiroshima University, 1-2-3 Kasumi, Minami-ku, Hiroshima 734-8553, Japan.
Molecules. 2021 Apr 2;26(7):2035. doi: 10.3390/molecules26072035.
Persistent pain following orofacial surgery is not uncommon. High mobility group box 1 (HMGB1), an alarmin, is released by peripheral immune cells following nerve injury and could be related to pain associated with trigeminal nerve injury. Distal infraorbital nerve chronic constriction injury (dIoN-CCI) evokes pain-related behaviors including increased facial grooming and hyper-responsiveness to acetone (cutaneous cooling) after dIoN-CCI surgery in mice. In addition, dIoN-CCI mice developed conditioned place preference to mirogabalin, suggesting increased neuropathic pain-related aversion. Treatment of the infraorbital nerve with neutralizing antibody HMGB1 (anti-HMGB1 nAb) before dIoN-CCI prevented both facial grooming and hyper-responsiveness to cooling. Pretreatment with anti-HMGB1 nAb also blocked immune cell activation associated with trigeminal nerve injury including the accumulation of macrophage around the injured IoN and increased microglia activation in the ipsilateral spinal trigeminal nucleus caudalis. The current findings demonstrated that blocking of HMGB1 prior to nerve injury prevents the onset of pain-related behaviors, possibly through blocking the activation of immune cells associated with the nerve injury, both within the CNS and on peripheral nerves. The current findings further suggest that blocking HMGB1 before tissue injury could be a novel strategy to prevent the induction of chronic pain following orofacial surgeries.
口腔颌面外科手术后的持续性疼痛并不罕见。警报素高迁移率族蛋白B1（HMGB1）在神经损伤后由外周免疫细胞释放，可能与三叉神经损伤相关的疼痛有关。小鼠眶下神经远端慢性压迫损伤（dIoN-CCI）手术后会引发疼痛相关行为，包括面部梳理增加以及对丙酮（皮肤冷却）的超敏反应。此外，dIoN-CCI小鼠对米罗加巴林产生条件性位置偏爱，表明神经病理性疼痛相关的厌恶感增加。在dIoN-CCI手术前用中和抗体HMGB1（抗HMGB1单克隆抗体）处理眶下神经可预防面部梳理和对冷却的超敏反应。抗HMGB1单克隆抗体预处理还可阻断与三叉神经损伤相关的免疫细胞激活，包括损伤的眶下神经周围巨噬细胞的聚集以及同侧三叉神经尾侧核中小胶质细胞激活的增加。目前的研究结果表明，在神经损伤前阻断HMGB1可预防疼痛相关行为的发生，可能是通过阻断中枢神经系统内和外周神经上与神经损伤相关的免疫细胞激活来实现的。目前的研究结果进一步表明，在组织损伤前阻断HMGB1可能是预防口腔颌面外科手术后慢性疼痛诱导的一种新策略。
