Introduction: Nucleus cuneiformis (NCF), as part of descending pain inhibitory system, cooperates with periaqueductal gray (PAG) and rostral ventromedial medulla (RVM) in supraspinal modulation of pain. Cannabinoids have analgesic effects in the PAG, RVM and NCF. The transient receptor potential vanilloid type 1 (TRPV1) can be activated by anandamide and WIN55, 212-2 as a cannabinoid receptor agonist. The aim of the current study is to investigate the possible interplay between the cannabinoid and vanilloid systems for modulation of pain at the NCF.Methods: In this study, a cannabinoid receptor agonist, WIN55, 212-2 (15 mg/0.3 ml DMSO), and selective TRPV1 receptor antagonist, capsazepine (10, 25, 50 and 100 nmol/0.3 ml DMSO), were microinjected bilaterally into the NCF, and tailflick and formalin tests were used to assess the animal’s pain-related behaviors at 5-min intervals for a 60-min period.Results: Our findings demonstrated that analgesic effect of WIN55, 212-2 were dose-dependently attenuated by capsazepine in both tests. In the Tail-flick test, capsazepine at both doses of 50 (P<0.01) and 100 (P<0.001) nmol could significantly prevent the antinociceptive effect of WIN55, 212-2 while capsazepine, in formalin test, could decreased its antinociceptive effect at the dose of 50 nmol (P<0.05) as well. On the other hand, solely administration of the highest dose of capsazepine in both tests did not alter the pain-related behaviors.Discussion: It suggests a possible role for TRPV1 receptors in NCF-mediated cannabinoid-induced antinociception.

Background: Intense stress can change pain perception and induce hyperalgesia; a phenomenon called stress-induced hyperalgesia (SIH). However, the neurobiological mechanism of this effect remains unclear. The present study aimed to investigate the effect of the spinal cord μ-opioid receptors (MOR) and α 2-adrenergic receptors (α 2-AR) on pain sensation in rats with SIH. Methods: Eighteen Sprague-Dawley male rats, weighing 200-250 g, were randomly divided into two groups (n=9 per group), namely the control and stress group. The stress group was evoked by random 1-hour daily foot-shock stress (0. 8 mA for 10 seconds, 1 minute apart) for 3 weeks using a communication box. The Tail-flick and formalin tests were performed in both groups on day 22. The real-time RT-PCR technique was used to observe MOR and α 2-AR mRNA levels at the L4-L5 lumbar spinal cord. Statistical analysis was performed using the GraphPad Prism 5 software (San Diego, CA, USA). Student’ s t test was applied for comparisons between the groups. P<0. 05 was considered statistically significant. Results: There was a significant (P=0. 0014) decrease in tailflick latency in the stress group compared to the control group. Nociceptive behavioral responses to formalin-induced pain in the stress group were significantly increased in the acute (P=0. 007) and chronic (P=0. 001) phases of the formalin test compared to the control group. A significant reduction was also observed in MOR mRNA level of the stress group compared to the control group (P=0. 003). There was no significant difference in α 2-AR mRNA level between the stress and control group. Conclusion: The results indicate that chronic stress can affect nociception and lead to hyperalgesia. The data suggest that decreased expression of spinal cord MOR causes hyperalgesia.