TNFalpha mechanically sensitizes masseter muscle nociceptors by increasing prostaglandin E2 levels.

摘要

TNFalpha induces mechanical sensitization of rat masseter muscle nociceptors, which takes 2-3 h to manifest and is mediated through activation of P55 and P75 receptors. This study was undertaken to determine whether TNFalpha induces nociceptor mechanical sensitization through the release of other algogenic substances such as glutamate, prostaglandin E(2) (PGE(2)), and/or nerve growth factor (NGF), which have been shown to induce mechanical sensitization of muscle nociceptors. Masseter muscle homogenate levels of PGE(2) and NGF were measured 3 h after injection of TNFalpha (1 mug) or vehicle control using commercially available kits. Interstitial glutamate concentration was measured after injection of TNFalpha or vehicle control using a glutamate-selective biosensor probe. Diclofenac, a cyclooxygenase inhibitor that blocks the synthesis of PGE(2), D-2-amino-5-phosphonovaleric acid (APV), a competitive N-methyl-D-aspartate (NMDA) receptor antagonist, and a tyrosine kinase A (TrkA) receptor antibody, which blocks NGF-induced masseter muscle nociceptor sensitization, were used to assess the contribution of PGE(2), glutamate, and NGF to TNFalpha-induced nociceptor sensitization. PGE(2) and glutamate concentrations were significantly elevated 3 h after TNFalpha injection into the masseter muscle. Injection of diclofenac partially reversed the TNFalpha-induced decreases in the mechanical threshold (MT) of masseter muscle nociceptors, whereas vehicle control, APV, and TrkA antibody did not significantly alter nociceptor MT. These results suggest that TNFalpha-induced mechanical sensitization of masseter muscle nociceptors is mediated in part by increased PGE(2) levels. The findings of this study support the hypothesis that TNFalpha induces a delayed mechanical sensitization of masseter muscle nociceptors indirectly by the release of PGE(2).