An analgesia circuit activated by cannabinoids

• Published in: Nature (London) Vol. 395; no. 6700; pp. 381 - 383
• Main Authors: Meng, Ian D, Manning, Barton H, Martin, William J, Fields, Howard L
• Format: Journal Article
• Language: English
• Published: London Nature Publishing 24.09.1998; Nature Publishing Group
• Subjects: Analgesia; Analgesics, Non-Narcotic - pharmacology; Animals; Benzoxazines; Biological and medical sciences; Brain; Cannabinoids - pharmacology; Fundamental and applied biological sciences. Psychology; GABA Agonists - administration & dosage; Inactivation; Male; Marijuana; Medical research; Medulla Oblongata - drug effects; Medulla Oblongata - physiology; Morphine - pharmacology; Morpholines - administration & dosage; Motor Activity - drug effects; Muscimol - administration & dosage; Naphthalenes - administration & dosage; Neural Pathways - drug effects; Neurology; Neurons - drug effects; Neurons - physiology; Pain; Piperidines - administration & dosage; Pyrazoles - administration & dosage; Rats; Rats, Sprague-Dawley; Receptors, Cannabinoid; Receptors, Drug - agonists; Receptors, Drug - antagonists & inhibitors; Rimonabant; Somesthesis and somesthetic pathways (proprioception, exteroception, nociception); interoception; electrolocation. Sensory receptors; Vertebrates: nervous system and sense organs; Nociception; Rat; Brain stem; Motor system disorder; Rodentia; Central nervous system; Discharge pattern; Electrophysiology; Anatomy; Cannabinoid; Analgesia; Vertebrata; Mammalia; Pain; Tail flick test; Medulla oblongata; Mechanism of action; Motricity; Brain (vertebrata)
• ISSN: 0028-0836; 1476-4687
• DOI: 10.1038/26481

Although many anecdotal reports indicate that marijuana and its active constituent, delta-9-tetrahydrocannabinol (delta-9-THC), may reduce pain sensation,, studies of humans have produced inconsistent results. In animal studies, the apparent pain-suppressing effects of delta-9-THC and other cannabinoid drugs are confounded by motor deficits,. Here we show that a brainstem circuit that contributes to the pain-suppressing effects of morphine is also required for the analgesic effects of cannabinoids. Inactivation of the rostral ventromedial medulla (RVM) prevents the analgesia but not the motor deficits produced by systemically administered cannabinoids. Furthermore, cannabinoids produce analgesia by modulating RVM neuronal activity in a manner similar to, but pharmacologically dissociable from, that of morphine. We also show that endogenous cannabinoids tonically regulate pain thresholds in part through the modulation of RVM neuronal activity. These results show that analgesia produced by cannabinoids and opioids involves similar brainstem circuitry and that cannabinoids are indeed centrally acting analgesics with a new mechanism of action.