Activation of TRPV1 and TRPA1 leads to muscle nociception and mechanical hyperalgesia.

Activation of TRPV1 and TRPA1 leads to muscle nociception and mechanical hyperalgesia.
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DOI:
10.1016/j.pain.2009.04.021
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发表时间:
2009-08
期刊:
影响因子:
7.4
通讯作者:
Zhang Y
Zhang Y
中科院分区:
医学1区
文献类型:
--
作者:
Ro JY;Lee JS;Zhang Y

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在雄性 Sprague Dawley 大鼠中研究了 TRPV1 和 TRPA1 在介导颅面肌肉伤害感受和机械痛觉过敏中的作用。首先,我们证实了TRPV1在大鼠三叉神经节(TG)咬肌传入神经中的表达,并在双标记免疫组化实验中提供了TRPA1也在支配咀嚼肌的初级传入神经中表达的新数据。然后,我们使用专门为颅面系统设计和验证的行为模型,检查咬肌中每个 TRP 通道的激活是否会引起急性伤害反应,并导致咬肌对机械刺激过敏。分别肌内注射 TRPV1 和 TRPA1 特异性激动剂、辣椒素和芥子油 (MO),产生立即的伤害性后爪反应,随后以浓度依赖性方式产生长时间的机械痛觉过敏。用 TRPV1 拮抗剂辣椒西平对肌肉进行预处理,可有效减弱辣椒素引起的肌肉伤害感受和机械痛觉过敏。同样,用选择性 TRPA1 拮抗剂 AP18 对肌肉进行预处理,可显着阻断 MO 诱导的肌肉伤害感受和机械痛觉过敏。我们分别用另一组 TRPV1 和 TRPA1 选择性拮抗剂 AMG9810 和 HC030031 证实了这些数据。总的来说,这些结果提供了令人信服的证据,证明 TRPV1 和 TRPA1 可以在功能上促进肌肉伤害感受和痛觉过敏,并表明肌肉传入细胞中表达的 TRP 通道可以参与病理性肌肉疼痛状况的发展。
The involvement of TRPV1 and TRPA1 in mediating craniofacial muscle nociception and mechanical hyperalgesia was investigated in male Sprague Dawley rats. First, we confirmed the expression of TRPV1 in masseter afferents in rat trigeminal ganglia (TG), and provided new data that TRPA1 is also expressed in primary afferents innervating masticatory muscles in double-labeling immunohistochemistry experiments. We then examined whether activation of each TRP channel in the masseter muscle evokes acute nocifensive responses and leads to the development of masseter hypersensitivity to mechanical stimulation using the behavioral models that have been specifically designed and validated for the craniofacial system. Intramuscular injections with specific agonists for TRPV1 and TRPA1, capsaicin and mustard oil (MO), respectively, produced immediate nocifensive hindpaw responses followed by prolonged mechanical hyperalgesia in a concentration-dependent manner. Pretreatment of the muscle with a TRPV1 antagonist, capsazepine, effectively attenuated the capsaicin-induced muscle nociception and mechanical hyperalgesia. Similarly, pretreatment of the muscle with a selective TRPA1 antagonist, AP18, significantly blocked the MO-induced muscle nociception and mechanical hyperalgesia. We confirmed these data with another set of selective antagonist for TRPV1 and TRPA1, AMG9810 and HC030031, respectively. Collectively, these results provide compelling evidence that TRPV1 and TRPA1 can functionally contribute to muscle nociception and hyperalgesia, and suggest that TRP channels expressed in muscle afferents can engage in the development of pathologic muscle pain conditions.
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