Li Ziyuan, Gan Yu, Kang Ting, Zhao Yi, Huang Tianguang, Chen Yuhao, Liu Jin, Ke Bowen
Department of Anesthesiology, Laboratory of Anesthesia and Critical Care Medicine, National-Local Joint Engineering Research Centre of Translational Medicine of Anesthesiology, West China Hospital, Sichuan University, Chengdu, Sichuan, People's Republic of China.
Frontiers Science Center for Disease-Related Molecular Network, Sichuan University West China Hospital, Sichuan University, Chengdu, Sichuan, People's Republic of China.
J Pain Res. 2023 Mar 10;16:785-795. doi: 10.2147/JPR.S398607. eCollection 2023.
The treatment of neuropathic pain is still a major troublesome clinical problem. The existing therapeutic drugs have limited analgesic effect and obvious adverse reactions, which presents opportunities and challenges for the development of new analgesic drugs. Camphor, a kind of monoterpene, has been shown anti-inflammatory and analgesic effects in traditional Chinese medicine. But we know little about its effect in neuropathic pain. In this article, We have verified the reliable analgesic effect of camphor in the neuropathic pain model caused by different predispositions.
The nociceptive response of mice was induced by transient receptor potential A1 (TRPA1) agonist to verify the effect of camphor on the nociceptive response. Multiple paclitaxel (PTX) injection models, Single oxaliplatin (OXA) injection models, Chronic constriction injury (CCI) models and Streptozotocin-induced (STZ) diabetic neuropathic pain models were used in this study. We verified the analgesic effect of camphor in mice by acetone test and conditioned place aversion test. At the same time, comparing the adverse reaction of nervous system between camphor and pregabalin at equivalent dose in locomotor activity test and rotarod test. Using patch clamp to verify the effect of camphor on dorsal root ganglion (DRG) excitability.
In behavioral test, compared with vehicle group, camphor significantly reduced the spontaneous nociception caused by TRPA1 agonist-formalina and allyl isothiocyanate (AITC). Compared with vehicle group, camphor significantly reduced the flinching and licking time in neuropathic pain model mice, including PTX, OXA, STZ and CCI induced peripheral neuralgia models. Compared with vehicle group, pregabalin significantly increased the resting time and reduced the average speed without resting and distance in locomotor activity test, reduced the time stayed on rotarod in rotarod test. In patch clamp test, compared with vehicle group, camphor significantly reduced the action potential (AP) firing frequency of DRG.
Camphor can alleviate the symptoms of hyperalgesia in various neuropathic pain models, and has no obvious adverse reactions compared with pregabalin. This effect is related to the down-regulation of DRG neuron excitability.
神经性疼痛的治疗仍然是一个主要的棘手临床问题。现有的治疗药物镇痛效果有限且不良反应明显，这为新型镇痛药的研发带来了机遇和挑战。樟脑是一种单萜类化合物，在传统中药中已显示出抗炎和镇痛作用。但我们对其在神经性疼痛中的作用了解甚少。在本文中，我们验证了樟脑在不同诱发因素所致神经性疼痛模型中的可靠镇痛效果。
通过瞬时受体电位A1（TRPA1）激动剂诱导小鼠的伤害性反应，以验证樟脑对伤害性反应的影响。本研究采用多次紫杉醇（PTX）注射模型、单次奥沙利铂（OXA）注射模型、慢性缩窄损伤（CCI）模型和链脲佐菌素诱导（STZ）的糖尿病性神经病理性疼痛模型。我们通过丙酮试验和条件性位置厌恶试验验证了樟脑对小鼠的镇痛效果。同时，在运动活动试验和转棒试验中比较樟脑与等效剂量普瑞巴林在神经系统不良反应方面的差异。采用膜片钳技术验证樟脑对背根神经节（DRG）兴奋性的影响。
在行为学试验中，与溶剂对照组相比，樟脑显著降低了TRPA1激动剂 - 福尔马林和异硫氰酸烯丙酯（AITC）引起的自发伤害感受。与溶剂对照组相比，樟脑显著减少了神经性疼痛模型小鼠的缩足和舔舐时间，包括PTX、OXA、STZ和CCI诱导的周围神经痛模型。与溶剂对照组相比，普瑞巴林在运动活动试验中显著增加了静止时间，降低了无静止状态下的平均速度和移动距离，在转棒试验中减少了在转棒上停留的时间。在膜片钳试验中，与溶剂对照组相比，樟脑显著降低了DRG的动作电位（AP）发放频率。
樟脑可减轻各种神经性疼痛模型中的痛觉过敏症状，与普瑞巴林相比无明显不良反应。这种作用与DRG神经元兴奋性的下调有关。
