Inhibition of glutamatergic transmission by morphine in the basolateral amygdaloid nucleus reduces pain-induced aversion.
We examined the role of glutamatergic transmission within the basolateral amygdaloid nucleus (BLA) in pain-induced aversion using a conditioned place paradigm and an in vivo microdialysis technique in rats. Microinjection of MK-801 (1 or 10 nmol/side) into the bilateral BLA 5 min before intraplantar injection of formalin dose-dependently attenuated formalin-induced conditioned place aversion (F-CPA) without affecting nociceptive behaviors, such as lifting, licking, and biting. On the contrary, microinjection of neither CNQX (30 nmol/side) nor AP-3 (30 nmol/side) showed any significant effect on F-CPA. Microdialysis experiments revealed that intraplantar injection of formalin induced an increase in the extracellular glutamate level within the BLA. This increase in glutamate was suppressed by morphine perfusion (100 microM) via the microdialysis probe. Moreover, intra-BLA injection of morphine (10 microg/side) 5 min before formalin injection attenuated F-CPA without affecting nociceptive behaviors. These results suggest that glutamatergic transmission via NMDA receptors in the BLA plays a crucial role in the pain-induced aversion, and that in addition to the well-characterized effects on the sensory component of pain, morphine also influences the affective component of pain through an inhibitory effect on intra-BLA glutamatergic transmission.
Department of Pharmacology, Graduate School of Pharmaceutical Sciences, Hokkaido University, Sapporo 060-0812, Japan.
Satoshi
S
Deyama
Junki
J
Yamamoto
Taiichi
T
Machida
Sachi
S
Tanimoto
Takayuki
T
Nakagawa
Shuji
S
Kaneko
Masamichi
M
Satoh
Masabumi
M
Minami
D000679:Amygdala / Q000187:drug effects / Q000378:metabolism*; D000701:Analgesics, Opioid / Q000494:pharmacology; D000818:Animals; D001362:Avoidance Learning / Q000187:drug effects / Q000502:physiology; D004305:Dose-Response Relationship, Drug; D018691:Excitatory Amino Acid Antagonists / Q000494:pharmacology; D045604:Extracellular Fluid / Q000378:metabolism; D005239:Fear / Q000187:drug effects / Q000502:physiology*; D018698:Glutamic Acid / Q000032:analysis / Q000378:metabolism*; D008297:Male; D017551:Microdialysis; D009020:Morphine / Q000494:pharmacology*; D009433:Neural Inhibition / Q000187:drug effects / Q000502:physiology; D010146:Pain / Q000188:drug therapy / Q000503:physiopathology / Q000523:psychology*; D010147:Pain Measurement / Q000187:drug effects; D017288:Pain Threshold / Q000187:drug effects / Q000502:physiology; D051381:Rats; D017207:Rats, Sprague-Dawley; D016194:Receptors, N-Methyl-D-Aspartate / Q000037:antagonists & inhibitors / Q000378:metabolism; D009435:Synaptic Transmission / Q000187:drug effects / Q000502:physiology*; D015854:Up-Regulation / Q000187:drug effects / Q000502:physiology
D000701:Analgesics, Opioid; D018691:Excitatory Amino Acid Antagonists; D016194:Receptors, N-Methyl-D-Aspartate; D018698:Glutamic Acid; D009020:Morphine