Alvarez P, Levine J D
Department of Oral and Maxillofacial Surgery, University of California San Francisco, San Francisco, CA, USA.
Department of Oral and Maxillofacial Surgery, University of California San Francisco, San Francisco, CA, USA; Department of Medicine, University of California San Francisco, San Francisco, CA, USA.
Neuroscience. 2015 Dec 17;311:499-507. doi: 10.1016/j.neuroscience.2015.10.059. Epub 2015 Nov 5.
Persistent muscle pain is a common and disabling symptom for which available treatments have limited efficacy. Since tetrodotoxin (TTX) displays a marked antinociceptive effect in models of persistent cutaneous pain, we tested its local antinociceptive effect in rat models of muscle pain induced by inflammation, ergonomic injury and chemotherapy-induced neuropathy. While local injection of TTX (0.03-1 μg) into the gastrocnemius muscle did not affect the mechanical nociceptive threshold in naïve rats, exposure to the inflammogen carrageenan produced a marked muscle mechanical hyperalgesia, which was dose-dependently inhibited by TTX. This antihyperalgesic effect was still significant at 24h. TTX also displayed a robust antinociceptive effect on eccentric exercise-induced mechanical hyperalgesia in the gastrocnemius muscle, a model of ergonomic pain. Finally, TTX produced a small but significant inhibition of neuropathic muscle pain induced by systemic administration of the cancer chemotherapeutic agent oxaliplatin. These results indicate that TTX-sensitive sodium currents in nociceptors play a central role in diverse states of skeletal muscle nociceptive sensitization, supporting the suggestion that therapeutic interventions based on TTX may prove useful in the treatment of muscle pain.
持续性肌肉疼痛是一种常见且使人丧失能力的症状，现有的治疗方法疗效有限。由于河豚毒素（TTX）在持续性皮肤疼痛模型中显示出显著的抗伤害感受作用，我们在由炎症、劳损性损伤和化疗引起的神经病变所导致的肌肉疼痛大鼠模型中测试了其局部抗伤害感受作用。虽然向腓肠肌局部注射TTX（0.03 - 1μg）对未处理的大鼠的机械性伤害感受阈值没有影响，但暴露于炎症介质角叉菜胶会产生显著的肌肉机械性痛觉过敏，而TTX可剂量依赖性地抑制这种痛觉过敏。这种抗痛觉过敏作用在24小时时仍然显著。TTX对腓肠肌中离心运动诱导的机械性痛觉过敏（一种劳损性疼痛模型）也显示出强大的抗伤害感受作用。最后，TTX对全身给予癌症化疗药物奥沙利铂所诱导的神经性肌肉疼痛产生了轻微但显著的抑制作用。这些结果表明，伤害感受器中对TTX敏感的钠电流在骨骼肌伤害感受敏化的多种状态中起核心作用，这支持了基于TTX的治疗干预可能被证明对治疗肌肉疼痛有用的观点。
