Mirogabalin alleviates nociceptive hypersensitivity without causing sedation in a mouse model of post-traumatic trigeminal neuropathy
Mirogabalin alleviates nociceptive hypersensitivity without causing sedation in a mouse model of post-traumatic trigeminal neuropathy
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DOI：
10.1016/j.bbr.2022.113829
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发表时间：
2022-03-13
影响因子：
2.7
通讯作者：
Morioka, Norimitsu
中科院分区：
文献类型：
--
作者：
Kochi, Takahiro;Nakamura, Yoki;Morioka, Norimitsu
创伤后三叉神经病(PTTN)是一种慢性感觉障碍，患者因口腔和牙科手术或颈部面部创伤而导致神经损伤。目前，PTTN缺乏有效的治疗策略，接受常规药物治疗的PTTN患者会出现嗜睡和药物成瘾等不良反应。在本研究中，我们研究了一种新的加巴喷丁类化合物米罗巴林是否能有效地治疗小鼠远端眶下神经慢性压迫损伤(Dion-CCI)所致的PTTN。在Dion-CCI小鼠中观察到面部美容时间增加和对丙酮的高反应性。这些疼痛相关行为可通过腹腔注射米高巴林来减轻。特别是，米洛卡林显著减少了面部美容时间的增加。注射后45min开始有镇痛作用，持续6h。此外，在旷场实验中，10 mg/kg的米罗巴林对小鼠的运动活动无明显影响，提示其不具有镇静作用。综上所述，目前的研究结果表明，米罗卡林可能是治疗口腔面部手术后PTTN的一种有价值的药物，没有镇静副作用。
Post-traumatic trigeminal neuropathy (PTTN) is a chronic sensory disorder that afflicts patients with nerve injury caused by orofacial and dental surgery or cervicofacial trauma. Currently, effective treatment strategies for PTTN are lacking, and patients treated with conventional drugs for PTTN experience adverse effects such as drowsiness and drug addiction. In the present study, we investigated whether mirogabalin, a novel gabapentinoid, could be an effective treatment for PTTN induced by distal infraorbital nerve chronic constriction injury (dIoN-CCI) in the mouse. Increased facial grooming time and hyper-responsiveness to acetone were observed in dIoN-CCI mice. These pain-related behaviors were attenuated by intraperitoneal injection of mirogabalin. In particular, mirogabalin significantly diminished the increase in facial grooming time. The analgesic effect of mirogabalin injection started 45 min after the injection and persisted for 6 h. Additionally, 10 mg/kg mirogabalin did not affect locomotor activity in the open field test, suggesting that it does not cause sedation. Together, the current findings suggest that mirogabalin could be a valuable therapeutic drug for PTTN following orofacial surgeries without sedative side effects.