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 PGE₂, 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 PGE₂, 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.

本研究旨在评估慢性潜伏性肌肉痛觉过敏的发展和/或维持是否受 P2X3 受体调节。我们还评估了这些过程中背根神经节的 P2X3 受体和 PKCε 的表达。由角叉菜胶诱导并由 PGE ₂证明的慢性潜伏性肌肉痛觉过敏小鼠模型，被使用。机械性肌肉痛觉过敏由 Randall-Selitto 镇痛计测量。通过肌内或鞘内注射使用选择性 P2X3 受体拮抗剂 A-317491 分析 P2X3 受体的参与情况。通过蛋白质印迹评估 P2X3 和 PKCε 在背根神经节 (L4-S1) 中的表达。先前对角叉菜胶的 P2X3 受体鞘内阻断阻止了急性和慢性潜伏性肌肉痛觉过敏的发展和维持，而先前对角叉菜胶的 P2X3 受体的肌内阻断仅减少了急性肌肉痛觉过敏，而对慢性潜伏性肌肉痛觉过敏没有影响。在 PGE ₂之前立即鞘内但不是肌肉内阻断 P2X3 受体，在先前被角叉菜胶致敏的动物中，逆转了慢性潜伏性肌肉痛觉过敏。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。在脊髓背角上表达的 P2X3 受体有助于从急性肌肉疼痛转变为慢性肌肉疼痛。我们还建议在此过程中 PKCε 和 P2X3 受体相互作用。因此，我们指出脊髓背角的 P2X3 受体是预防或逆转慢性肌肉疼痛状况的药理学靶点。