Descending serotonergic pathways and spinal 5‐HT7 receptors mediate systemically administered opioid and cannabinoid analgesia, and swim stress‐induced opioid and nonopioid analgesia

Objective: The spinal 5‐HT7 receptors play an important role in both morphine and cannabinoid‐induced analgesia. Stress can produce analgesia, termed stress induced analgesia (SIA) and two form of SIA were identified; opioid and nonopioid. An endocannabinoid mechanism for stress‐induced nonopioid analgesia was revealed. In this study, we aimed to clarify the role of spinal 5‐HT7 receptors and descending serotonergic system in opioid and cannabinoid analgesia, and opioid and nonopioid SIA. Methods: Analgesia was measured by radiant tail‐flick test in BALB/c mice. Morphine, an opioid receptor agonist, and WIN 55, 212‐2, a cannabinoid agonist, and SB 269970, a 5‐HT7 receptor antagonist were used. The depletion of spinal 5‐HT was performed via intrathecal (i.th.) injection of 5,7 dihydroxytryptamine (5, 7‐DHT). To induce SIA, the mice were forced to swim in water at 32 °C or 20 °C for 2 min, respectively. Results: Both morphine and WIN 55, 212‐2 (10 mg/kg, s.c.) produced analgesic effects which were completely blocked by SB 269970 (10 μg, i.th.). Forced swims in 32 °C and 20 °C both induced analgesia which only 32 °C one was blocked with naloxone (10 mg/kg, s.c.). Both 32 °C and 20 °C swim SIA were blocked by SB 269970 (10 μg, i.th.). Morphine and WIN 55, 212‐2 (10 mg/kg, s.c.) induced analgesia, and SIA in 32 °C and 20 °C were diminished in 5,7‐DHT(60 μg, i.th.) injected mice. Conclusion: Opioids and cannabinoids activate the similar serotonergic descending pathways via spinal 5‐HT7 receptors as opioid and nonopioid SIA to produce analgesia.