Activation and sensitization of C and Aδ afferent fibers mediated by P2X receptors in rat dorsal skin

The present study investigated the activation and sensitization effects of local injection of P2X receptor agonist α,β-methylene ATP (αβ-meATP) into the receptive fields of afferent fibers innervating dorsal hairy skin in anesthetized rats. Single unit activities of afferent fibers were recorded by means of isolation of the fiber filaments from the dorsal cutaneous nerve branch. A total of 237 fibers were obtained. Of these, 67 were classed as C fibers, 104 as Aδ fibers and 66 as Aβ fibers. When αβ-meATP (0.1-100 μM, 10 μl) was injected subcutaneously into the receptive fields of these units, C and Aδ fibers demonstrated a dose-related increase in the discharge rates of the response. The activated proportion of C and Aδ fibers with a response to the drug also increased with dose. However, Aβ fibers did not exhibit significant activation. Furthermore, injection of αβ-meATP (10 μl) at a concentration of 100 μM resulted in a significant decrease of mechanical thresholds in C and Aδ fibers compared with pre-injection baseline (P < 0.05). In control experiments, injection of the vehicle phosphate-buffered saline (PBS, 10 μl) had no effect on all units tested. αβ-meATP (100 μM, 10 μl) followed by pyridoxal phosphate-6-azophenyl-2′,4′-disulfonic acid (PPADS), a P2X receptor antagonist, successfully blocked the activation and sensitization effects of αβ-meATP on C and Aδ fibers tested. These results suggest that peripheral P2X receptors are involved in mediating peripheral excitation of C and Aδ fibers.