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

Research output: Contribution to journalArticlepeer-review

2 Citations (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.

Original languageEnglish
Article number144
Pages (from-to)1-13
Number of pages13
JournalBrain Sciences
Issue number2
Publication statusPublished - 2021 Feb


  • Mast cell
  • PAR-2
  • Postoperative pain
  • Protease-activated receptor 2
  • Tryptase

ASJC Scopus subject areas

  • Neuroscience(all)


Dive into the research topics of 'Nociceptive sensitization by activation of protease-activated receptor 2 in a rat model of incisional pain'. Together they form a unique fingerprint.

Cite this