Department of Anesthesiology and the Graduate Program in Neuroscience, The University of Cincinnati College of Medicine, Cincinnati, OH 45267-0531, USA.
Mol Pain. 2013 Jun 14;9:28. doi: 10.1186/1744-8069-9-28.
Both spinal and trigeminal somatosensory systems use the TRPM8 channel as a principal transducer for detecting cold stimuli. It is currently unclear whether this cold transducer may play a role in trigeminal neuropathic pain manifesting cold allodynia and hyperalgesia. In the present study, trigeminal neuropathy was induced by chronic constrictive nerve injury of the infraorbital nerve (ION-CCI). Behavioral responses to cold stimuli in orofacial regions were assessed by the newly developed orofacial operant test in the ION-CCI rats. We tested menthol and capsazepine, two compounds that can activate and inhibit TRPM8 respectively, on orofacial operant responses to cold stimuli in ION-CCI rats. Testing animals performed operant tasks by voluntarily contacting their orofacial regions to a cold stimulation module in order to access sweetened milk as a reward, and contact time and number of the operant behaviors were automatically recorded. Total contact time was significantly reduced at the cooling temperatures of 17°C and 12°C in ION-CCI group in comparison with sham group, indicating the presence of cold allodynia and hyperalgesia in ION-CCI rats. When menthol was administered to ION-CCI rats, total contact time was further reduced and total contact number increased at the cooling temperatures. In contrast, after administration of capsazepine to ION-CCI rats, total contact time was significantly increased at the cooling temperatures. The behavioral outcomes support the idea that TRPM8 plays a role in cold allodynia and hyperalgesia following chronic trigeminal nerve injury.
脊髓和三叉躯体感觉系统均使用 TRPM8 通道作为检测冷刺激的主要传感器。目前尚不清楚这种冷传感器是否在表现出冷感觉过敏和痛觉过敏的三叉神经病理性疼痛中起作用。在本研究中，通过眶下神经慢性缩窄性损伤（ION-CCI）诱导三叉神经病变。通过新开发的 ION-CCI 大鼠的口腔操作性测试评估口腔区域对冷刺激的行为反应。我们测试了薄荷醇和辣椒素，这两种化合物分别可以激活和抑制 TRPM8，以测试它们对 ION-CCI 大鼠冷刺激口腔操作性反应的影响。测试动物通过自愿接触口腔区域到冷刺激模块来执行操作性任务，以便获得加糖牛奶作为奖励，接触时间和操作行为的次数自动记录。与假手术组相比，ION-CCI 组在 17°C 和 12°C 的冷却温度下总接触时间明显减少，表明 ION-CCI 大鼠存在冷感觉过敏和痛觉过敏。当薄荷醇给予 ION-CCI 大鼠时，在冷却温度下总接触时间进一步减少，总接触次数增加。相比之下，当给予 ION-CCI 大鼠辣椒素后，在冷却温度下总接触时间显著增加。这些行为结果支持 TRPM8 在慢性三叉神经损伤后冷感觉过敏和痛觉过敏中起作用的观点。
