Nociceptive sensitization by activation of protease-activated receptor 2 in a rat model of incisional pain

Kanta Kido, Norika Katagiri, Hiromasa Kawana, Shigekazu Sugino, Masanori Yamauchi, Eiji Masaki

研究成果: Article査読

2 被引用数 (Scopus)


Postoperative pain and consequent inflammatory responses after tissue incision adversely affects many surgical patients due to complicated mechanisms. In this study, we examined whether activation of protease-activated receptor 2 (PAR-2), which is stimulated by tryptase from mast cells, elicits nociception and whether the PAR-2 antagonist could reduce incisional nociceptive responses in vivo and in vitro. The effects of a selective PAR-2 antagonist, N3-methylbutyryl-N-6-aminohexa-noyl-piperazine (ENMD-1068), pretreatment on pain behaviors were assessed after plantar incision in rats. The effects of a PAR-2 agonist, SLIGRL-NH2, on nociception was assessed after the injection into the hind paw. Furthermore, the responses of C-mechanosensitive nociceptors to the PAR-2 agonist were observed using an in vitro skin–nerve preparation as well. Intraplantar injection of SLIGRL-NH2 elicited spontaneous nociceptive behavior and hyperalgesia. Local administration of ENMD-1068 suppressed guarding behaviors, mechanical and heat hyperalgesia only within the first few hours after incision. SLIGRL-NH2 caused ongoing activity in 47% of C-mechanonociceptors in vitro. This study suggests that PAR-2 may support early nociception after incision by direct or in-direct sensitization of C-fibers in rats. Moreover, PAR-2 may play a regulatory role in the early period of postoperative pain together with other co-factors to that contribute to postoperative pain.

ジャーナルBrain Sciences
出版ステータスPublished - 2021 2月

ASJC Scopus subject areas

  • 神経科学(全般)


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