Analgesic effects of cannabinoid receptor agonist WIN55,212-2 in the nucleus cuneiformis in animal models of acute and inflammatory pain in rats

Nucleus cuneiformis (NCF) along with periaqueductal gray (PAG) and rostral ventromedial medulla (RVM) is a part of descending system for pain modulation. Cannabinoids have analgesic effects on the PAG and RVM. This study investigates the possible role of cannabinoids in pain modulation in the NCF. Cannabinoid agonist, WIN55,212-2 (5, 10 and 20 μg/0.3 μl DMSO per side), and selective cannabinoid CB1 receptor antagonist, AM251(1, 5 and 10 μg/0.3 μl DMSO per side), were microinjected alone or in succession. As models of acute and inflammatory pain, tail-flick and formalin test were utilized to examine the effects of these drugs on pain modulation in 5 min time blocks for 60 min. Results of tail-flick and formalin tests demonstrated a dose-dependent analgesic effects for WIN55,212-2, with the most significant response at the dose of 20 μg/side. The analgesic responses were more effective during the first 45-min period of the tail-flick test (P < 0.001) and during the late phase (P < 0.001) of formalin test, compared to the early phase (P < 0.05). These analgesic effects were blocked in the presence of AM251 (1 μg/0.3 μl DMSO per side) in both tests. Administration of AM251 alone did not have any effect on nociceptive responses in either test. The cannabinoid-mediated analgesia demonstrated in this study suggests the presence of a cannabinoid-sensitive nociceptive modulatory system in the NCF.

► Intra-NCF cannabinoid receptor agonist decreased pain-related behaviors in rat.
► Intra-NCF AM251, cannabinoid CB1 receptor antagonist, had no nociceptive action.
► Intra-NCF AM251 dose-dependently decreased WIN55,212-induced antinociception.