Endogenous opioid and cannabinoid systems contribute to antinociception produced by administration of NSAIDs into the insular cortex of rats

• Published in: Biomedicine & pharmacotherapy 2020-11, Vol.131, p.110722-110722, Article 110722
• Main Authors: Tsagareli, Natia, Tsiklauri, Nana, Kvachadze, Irine, Tsagareli, Merab G.
• Format: Article
• Language: English
• Subjects: Analgesia; Animals; Anti-Inflammatory Agents, Non-Steroidal - pharmacology; Cerebral Cortex - drug effects; Cerebral Cortex - physiology; Descending modulation; Endocannabinoids - physiology; Hyperalgesia; Male; Naloxone - pharmacology; Nociception; Nociception - drug effects; Nociception - physiology; Non-opioids; Opioid Peptides - physiology; Piperidines - pharmacology; Pyrazoles - pharmacology; Rats; Rats, Wistar; Somatostatin - analogs & derivatives; Somatostatin - pharmacology; Withdrawal reflexes
• ISSN: 0753-3322; 1950-6007
• DOI: 10.1016/j.biopha.2020.110722

Post-treatment (A) or Pre-treatment (B) with opioid receptors’ antagonists naloxone or CTOP or cannabinoid (CB1) recepror’s antagonis AM-251 injected into the anterior cingulate cortex of the rat brain blocks analgesic effects of NSAIDs in latencies of the thermal paw withdrawal reflex and thresholds of the mechanical paw withdrawal reflex for post-formalin phase II. [Display omitted] •Non-opioids-induced antinociception in insula involves endo-opioids and cannabinoids.•Endo-opioids and cannabinoids action is attenuated by their receptors’ antagonists.•This antinociception is mediated via descending endo-opioid and cannabinoid systems.•Descending endo-opioid and cannabinoid systems control spinal nociceptive reflexes. Pain sensation is characterized as a complex experience, dependent on sensory processes as well as the activation of limbic brain areas involved in emotion, among them anterior insula. This cortical area is involved in the perception and response to painful stimuli. We investigated if this area contributes to antinociception produced by NSAIDs, and underlying mechanisms. We found that administration of NSAIDs into the anterior insular cortex in rats reduced mechanical and heat hyperalgesia produced by intraplantar injection of formalin, and this was attenuated by pre- or post-treatment with the opioid receptor antagonists, naloxone and CTOP, and the cannabinoid receptor (CB1) antagonist AM-251. These data support the concept that NSAID-evoked antinociception is mediated via descending endogenous opioid and cannabinoid systems inhibiting spinal paw withdrawal reflexes in rodents.