Involvement of T-type calcium channels in the mechanism of low dose morphine-induced hyperalgesia in adult male rats

Abstract

It has been shown that systemic and local administration of ultra-low dose morphine induced a hyperalgesic response via mu-opioid receptors. However, its exact mechanism(s) has not fully been clarified. It is documented that mu-opioid receptors functionally couple to T-type voltage dependent Ca+2 channels. Here, we investigated the role of T-type calcium channels, amiloride and mibefradil, on the induction of low-dose morphine hyperalgesia in male Wistar rats. The data showed that morphine (0.01 μg i.t. and 1 μg/kg i.p.) could elicit hyperalgesia as assessed by the tail-flick test. Administration of amiloride (5 and 10 μg i.t.) and mibefradil (2.5 and 5 μg i.t.) completely blocked low-dose morphine-induced hyperalgesia in spinal dorsal horn. Amiloride at doses of 1 and 5 mg/kg (i.p.) and mibefradil (9 mg/kg ip) 10 min before morphine (1 μg/kg i.p.) inhibited morphine-induced hyperalgesia. Our results indicate a role for T-type calcium channels in low dose morphine-induced hyperalgesia in rats. © 2021 Elsevier Ltd