Laboratory of Pain and Inflammation Research, School of Applied Sciences, State University of Campinas (UNICAMP), Pedro Zaccaria 1300, Limeira, Sao Paulo, Brazil.
Laboratory of Biotechnology, School of Applied Sciences, State University of Campinas (UNICAMP), Limeira, São Paulo, Brazil.
Purinergic Signal. 2020 Sep;16(3):403-414. doi: 10.1007/s11302-020-09718-x. Epub 2020 Aug 6.
This study aimed to evaluate whether the development and/or maintenance of chronic-latent muscle hyperalgesia is modulated by P2X3 receptors. We also evaluate the expression of P2X3 receptors and PKCε of dorsal root ganglions during these processes. A mouse model of chronic-latent muscle hyperalgesia, induced by carrageenan and evidenced by PGE, was used. Mechanical muscle hyperalgesia was measured by Randall-Selitto analgesimeter. The involvement of P2X3 receptors was analyzed by using the selective P2X3 receptors antagonist A-317491 by intramuscular or intrathecal injections. Expression of P2X3 and PKCε in dorsal root ganglion (L4-S1) were evaluated by Western blotting. Intrathecal blockade of P2X3 receptors previously to carrageenan prevented the development and maintenance of acute and chronic-latent muscle hyperalgesia, while intramuscular blockade of P2X3 receptors previously to carrageenan only reduced the acute muscle hyperalgesia and had no effect on chronic-latent muscle hyperalgesia. Intrathecal, but not intramuscular, blockade of P2X3 receptors immediately before PGE, in animals previously sensitized by carrageenan, reversed the chronic-latent muscle hyperalgesia. There was an increase in total and phosphorylated PKCε 48 h after the beginning of acute muscle hyperalgesia, and in P2X3 receptors at the period of chronic muscle hyperalgesia. P2X3 receptors expressed on spinal cord dorsal horn contribute to transition from acute to chronic muscle pain. We also suggest an interaction of PKCε and P2X3 receptors in this process. Therefore, we point out P2X3 receptors of the spinal cord dorsal horn as a pharmacological target to prevent the development or reverse the chronic muscle pain conditions.
本研究旨在评估 P2X3 受体是否调节慢性潜伏性肌肉痛觉过敏的发展和/或维持。我们还评估了背根神经节在这些过程中 P2X3 受体和 PKCε 的表达。使用角叉菜胶诱导的慢性潜伏性肌肉痛觉过敏的小鼠模型，并通过 PGE 证实。通过 Randall-Selitto 镇痛计测量肌肉机械性痛觉过敏。通过肌肉内或鞘内注射选择性 P2X3 受体拮抗剂 A-317491 分析 P2X3 受体的参与。通过 Western blot 评估背根神经节（L4-S1）中 P2X3 和 PKCε 的表达。在角叉菜胶之前鞘内阻断 P2X3 受体可预防急性和慢性潜伏性肌肉痛觉过敏的发展和维持，而在角叉菜胶之前肌肉内阻断 P2X3 受体仅减轻急性肌肉痛觉过敏，对慢性潜伏性肌肉痛觉过敏没有影响。在预先用角叉菜胶敏化的动物中，在 PGE 之前立即鞘内阻断 P2X3 受体，可逆转慢性潜伏性肌肉痛觉过敏。在急性肌肉痛觉过敏开始后 48 小时，总 PKCε 和磷酸化 PKCε 增加，慢性肌肉痛觉过敏期间 P2X3 受体增加。脊髓背角的 P2X3 受体有助于从急性到慢性肌肉疼痛的转变。我们还建议在此过程中 PKCε 和 P2X3 受体之间存在相互作用。因此，我们指出脊髓背角的 P2X3 受体是预防发展或逆转慢性肌肉疼痛状况的药理学靶标。
