Role of opioid system in verapamil-induced antinociception in a rat model of orofacial pain

Abstract

Calcium, through its various channels involves in local, spinal and supra-spinal transmission of pain. In the present study, we investigated the separate and combined treatment effects of verapamil (a calcium channel blocker), morphine (an opioid agonist) and naloxone (an opioid antagonist) on pain in the orofacial region of rats. Orofacial pain was induced by subcutaneous (SC) injection of formalin (50 µL, 1.5%) into the left upper lip side, and the time durations spent face rubbing with epsilateral forepaw were recorded in three min blocks for a period of 45 min. Formalin induced a biphasic pattern (first phase: 0-3 min; second phase: 15-33 min) of pain. Intraperitoneal (IP) injections of verapamil (2 and 8 mg kg^-1) and morphine (2 and 4 mg kg^-1) suppressed orofacial pain. Co-administration of sub-analgesic doses of verapamil (0.5 mg kg^-1) and morphine (1 mg kg^-1) produced second phase analgesia. Both phases of formalin-induced pain were suppressed when an analgesic dose (2 mg kg^-1) of verapamil co-administered with a sub-analgesic dose (1 mg kg^-1) of morphine. The SC injection of naloxone (2 mg kg^-1) alone with no effect on pain intensity, prevented the antinociceptive effects induced by morphine (2 mg kg^-1), but not verapamil (2 mg kg^-1). The obtained results showed antinociceptive effects for verapamli and morphine on orofacial pain. Co-administrations of verapamil and morphine produced antinociceptive effects. It seems that opioid analgesic system may not have a role in the verapamil-induced antinociception.