Kinins’ Contribution to Postoperative Pain in an Experimental Animal Model and Its Implications

Abstract

Postoperative pain causes discomfort and disability, besides high medical costs. The search for better treatments for this pain is essential to improve recovery and reduce morbidity and risk of chronic postoperative pain. Kinins and their receptors contribute to different painful conditions and are among the main painful inflammatory mediators. We investigated the kinin’s role in a postoperative pain model in mice and reviewed data associating kinins with this painful condition. The postoperative pain model was induced by an incision in the mice’s paw’s skin and fascia with the underlying muscle’s elevation. Kinin levels were evaluated by enzyme immunoassays in sham or operated animals. Kinin’s role in surgical procedure-associated mechanical allodynia was investigated using systemic or local administration of antagonists of the kinin B1 receptor (DALBk or SSR240612) or B2 receptor (Icatibant or FR173657) and a kallikrein inhibitor (aprotinin). Kinin levels increased in mice’s serum and plantar tissue after the surgical procedure. All kinin B1 or B2 receptor antagonists and aprotinin reduced incision-induced mechanical allodynia. Although controversial, kinins contribute mainly to the initial phase of postoperative pain. The kallikrein–kinin system can be targeted to relieve this pain, but more investigations are necessary, especially associations with other pharmacologic targets.