Centhaquin attenuates hyperalgesia and non-evoked guarding in a rat model of postoperative pain primarily through α2B-adrenoceptors

Centhaquin has been shown to produce antinociception in the mouse hot plate and tail flick assays through the opioid, the alpha(2A) and alpha(2B) adrenoceptors. Present study was conducted to determine the effects of centhaquin in a rat model of postoperative pain. Involvement of opioid, and adrenergic receptors was assessed by pretreating rats with antagonists at the opioid (naloxone), alpha(2)-(atipamezole) or alpha(2B)-(imiloxan) adrenergic receptors. Postoperative pain was induced by hind paw plantar incision in male Sprague Dawley rats. Antihyperalgesic effects were determined by measurement of paw withdrawal latencies and withdrawal force, using dynamic von Frey filaments; attenuation of non-evoked guarding was measured by assigning pain scores to spontaneous behaviors. Rotarod test was used to determine motor impairment. Animals received saline, centhaquin or antagonist plus centhaquin. Centhaquin produced dose-dependent antihyperalgesic effect and attenuation of non-evoked guarding behavior, versus saline treated rats (P < 0.05). Naloxone partially blocked while atipamezole and imiloxan significantly reversed centhaquin's antihyperalgesic effects (P < 0.05). Attenuation of non-evoked guarding behavior was also blocked, but was not statistically significant. Imiloxan produced a greater block compared to atipamezole while naloxone had no significant effect. Rotarod testing indicated that centhaquin did not cause motor impairment. This is the first report demonstrating centhaquin antinociception in the rat postoperative pain model. Opioid, alpha(2) adrenergic, and particularly a2B adrenergic receptors are involved in mediating antihyperalgesia while attenuation of non-evoked guarding is mediated by alpha(2B)/alpha(2) adrenergic receptors. Centhaquin could be an effective non-sedating alternative in treating postoperative pain in ambulatory surgeries. (C) 2016 Elsevier B.V. All rights reserved.