Attenuation of cannabinoid-induced inhibition of medullary dorsal horn neurons by a kappa-opioid receptor antagonist.
The kappa-opioid receptor (KOR) antagonist norbinaltorphimine (nor-BNI) attenuates behavioral antinociception produced by spinal administration of the cannabinoid receptor agonist delta-9-tetrahydorcannabinol (THC). The present study examined the ability of nor-BNI to prevent cannabinoid-induced inhibition of medullary dorsal horn (MDH) nociceptive neurons and antinociception produced by the cannabinoid agonist WIN 55,212-2 (WIN-2). Extracellular, single-unit recordings of lamina I and lamina V MDH neurons were performed in urethane anesthetized rats. Heat-evoked activity was measured before and after local brainstem application of nor-BNI or vehicle followed by WIN-2. In both lamina I and lamina V neurons, prior application of nor-BNI prevented the inhibition of heat-evoked activity by WIN-2. In separate experiments, the contribution of KOR to cannabinoid-induced increases in heat-evoked head withdrawal latencies was assessed in lightly urethane-anesthetized rats. Antinociception produced by intrathecal administration of WIN-2 and THC was attenuated by prior administration of nor-BNI. In contrast, antinociception produced by the cannabinoid CP55940 remained unaffected by prior administration of nor-BNI. These results indicate that cannabinoid inhibition of nociceptive reflexes produced by WIN-2 and THC may result from inhibition of dorsal horn neurons through a KOR-dependent mechanism.
Okada-Ogawa
Akiko
A
Department of Oral Diagnosis, School of Dentistry, Nihon University, Kanda-Surugadai, Chiyoda-ku, Tokyo 101-8310, Japan.
Kurose
Masayuki
M
Meng
Ian D
ID
D000818:Animals; D048588:Benzoxazines / Q000494:pharmacology; D002121:Calcium Channel Blockers / Q000494:pharmacology; D002186:Cannabinoids / Q000494:pharmacology*; D013759:Dronabinol / Q000494:pharmacology; D008297:Male; D008526:Medulla Oblongata / Q000187:drug effects* / Q000378:metabolism; D009025:Morpholines / Q000494:pharmacology; D009271:Naltrexone / Q000031:analogs & derivatives* / Q000494:pharmacology; D009281:Naphthalenes / Q000494:pharmacology; D009292:Narcotic Antagonists / Q000494:pharmacology*; D018408:Patch-Clamp Techniques; D020671:Posterior Horn Cells / Q000187:drug effects* / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D017473:Receptors, Opioid, kappa / Q000037:antagonists & inhibitors*
D048588:Benzoxazines; D002121:Calcium Channel Blockers; D002186:Cannabinoids; D009025:Morpholines; D009281:Naphthalenes; D009292:Narcotic Antagonists; D017473:Receptors, Opioid, kappa; C051844:norbinaltorphimine; C070417:(3R)-((2,3-dihydro-5-methyl-3-((4-morpholinyl)methyl)pyrrolo-(1,2,3-de)-1,4-benzoxazin-6-yl)(1-naphthalenyl))methanone; D009271:Naltrexone; D013759:Dronabinol
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