Post-synaptic action of morphine on glutamatergic neuronal transmission related to the descending antinociceptive pathway in the rat thalamus.
Morphine is a prototypical mu-opioid receptor (MOR) agonist, and can directly inhibit pain transmission at both spinal and supraspinal levels. In the present study, we investigated the properties of thalamic neurons in an opioid-sensitive pain-modulating circuit. Application of morphine to cultured thalamic neurons evoked a potentiation of glutamate-induced peak currents, which was blocked by the MOR antagonist. Application of the protein kinase C inhibitor chelerythrine significantly inhibited the morphine-evoked enhancement of glutamate-induced currents. Immunoreactivity for MOR was observed with high density in the habenular nucleus (Hb) of the thalamus in rats, which was clearly co-localized with NMDA receptor subunit 1 (NRI). In this study, we show that microinjection of morphine into the Hb produced a dose-dependent increase in the tail-flick latency and enhanced the antinociceptive effect induced by the intra-Hb injection of glutamate. When fluoro-gold (FG) was used as a retrograde tracer, we found that FG-labeled neurons in the Hb after the microinjection of FG into the periaqueductal gray expressed both MOR and NR1. The present data suggest that the stimulation of MOR in the Hb may be involved in activation of the descending antinociceptive pathway through glutamatergic neurotransmission via the NMDA receptor.
Narita
Minoru
M
Department of Toxicology, Hoshi University School of Pharmacy and Pharmaceutical Sciences, Ebara, Shinagawa-ku, Tokyo, Japan. narita@hoshi.ac.jp
Hashimoto
Keisuke
K
Amano
Taku
T
Narita
Michiko
M
Niikura
Keiichi
K
Nakamura
Atsushi
A
Suzuki
Tsutomu
T
D000818:Animals; D004307:Dose-Response Relationship, Radiation; D004558:Electric Stimulation / Q000379:methods; D004622:Embryo, Mammalian; D018698:Glutamic Acid / Q000494:pharmacology; D007278:Injections, Spinal; D008297:Male; D008845:Microinjections; D009020:Morphine / Q000494:pharmacology*; D009294:Narcotics / Q000494:pharmacology*; D009457:Neuroglia; D009474:Neurons / Q000166:cytology*; D010146:Pain / Q000139:chemically induced / Q000188:drug therapy* / Q000503:physiopathology; D010147:Pain Measurement / Q000379:methods; D018408:Patch-Clamp Techniques / Q000379:methods; D010487:Periaqueductal Gray / Q000187:drug effects / Q000503:physiopathology; D051381:Rats; D017207:Rats, Sprague-Dawley; D017450:Receptors, Opioid, mu / Q000378:metabolism; D013266:Stilbamidines / Q000378:metabolism; D009435:Synaptic Transmission / Q000187:drug effects*; D013788:Thalamus / Q000166:cytology*
C049774:2-hydroxy-4,4'-diamidinostilbene, methanesulfonate salt; D009294:Narcotics; D017450:Receptors, Opioid, mu; D013266:Stilbamidines; D018698:Glutamic Acid; D009020:Morphine