Nociceptive Sensitization by Activation of Protease-Activated Receptor 2 in a Rat Model of Incisional Pain

Brain Sciences

Masanori Yamauchi¹  Shigekazu Sugino¹  Eiji Masaki²  Kanta Kido³  Norika Katagiri³  Hiromasa Kawana⁴ 

[1] Department of Anesthesiology and Perioperative Medicine, Tohoku University School of Medicine, Sendai, Miyagi 9808575, Japan;Department of Anesthesiology, International University of Health and Welfare Hospital, Nasushiobara, Tochigi 3292763, Japan;Department of Anesthesiology, Kanagawa Dental University Hospital, Yokosuka, Kanagawa 2388570, Japan;Department of Oral and Maxillofacial Implantology, Kanagawa Dental University Hospital, Yokosuka, Kanagawa 2388570, Japan;

关键词: postoperative pain;    protease-activated receptor 2;    PAR-2;    tryptase;    mast cell;   

DOI  :  10.3390/brainsci11020144

来源: DOAJ

【 摘 要 】

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-aminohexanoyl-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 indirect 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.

【 授权许可】

Unknown