Molecular interaction in the mouse PAG between NMDA and opioid receptors in morphine-induced acute thermal nociception.
Previous evidence demonstrates that low dose morphine systemic administration induces acute thermal hyperalgesia in normal mice through microOR stimulation of the inositol signaling pathway. We investigated the site of action of morphine and the mechanism of action of microOR activation by morphine to NMDA receptor as it relates to acute thermal hyperalgesia. Our experiments show that acute thermal hyperalgesia is blocked in periaqueductal gray with the microOR antagonist CTOP, the NMDA antagonist MK801 and the protein kinase C inhibitor chelerythrine. Therefore, a site of action of systemically administered morphine low dose on acute thermal hyperalgesic response appears to be located at the periaqueductal gray. At this supraspinal site, microOR stimulation by systemically morphine low dose administration leads to an increased phosphorylation of specific subunit of NMDA receptor. Our experiments show that the phosphorylation of subunit 1 of NMDA receptor parallels the acute thermal hyperalgesia suggesting a role for this subunit in morphine-induced hyperalgesia. Protein kinase C appears to be the key element that links microOR activation by morphine administration to mice with the recruitment of the NMDA/glutamatergic system involved in the thermal hyperalgesic response.
Ghelardini
Carla
C
Department of Clinical and Preclinical Pharmacology, University of Florence, Italy.
Galeotti
Nicoletta
N
Vivoli
Elisa
E
Norcini
Monica
M
Zhu
Wei
W
Stefano
George B
GB
Guarna
Massimo
M
Bianchi
Enrica
E
D000470:Alkaloids / Q000008:administration & dosage; D000704:Analysis of Variance; D000818:Animals; D001522:Behavior, Animal / Q000187:drug effects; D053119:Benzophenanthridines / Q000008:administration & dosage; D016291:Dizocilpine Maleate / Q000008:administration & dosage; D004305:Dose-Response Relationship, Drug; D004791:Enzyme Inhibitors; D018691:Excitatory Amino Acid Antagonists / Q000008:administration & dosage; D006930:Hyperalgesia / Q000139:chemically induced* / Q000473:pathology* / Q000517:prevention & control; D008297:Male; D051379:Mice; D009020:Morphine; D009043:Motor Activity / Q000187:drug effects; D010147:Pain Measurement / Q000379:methods; D010487:Periaqueductal Gray / Q000187:drug effects / Q000502:physiology*; D011597:Psychomotor Performance / Q000187:drug effects; D011930:Reaction Time / Q000187:drug effects; D016194:Receptors, N-Methyl-D-Aspartate / Q000502:physiology*; D017450:Receptors, Opioid, mu / Q000502:physiology*; D013004:Somatostatin / Q000008:administration & dosage / Q000031:analogs & derivatives
D000470:Alkaloids; D053119:Benzophenanthridines; D004791:Enzyme Inhibitors; D018691:Excitatory Amino Acid Antagonists; D016194:Receptors, N-Methyl-D-Aspartate; D017450:Receptors, Opioid, mu; C049352:phenylalanyl-cyclo(cysteinyltyrosyl-tryptophyl-ornithyl-threonyl-penicillamine)threoninamide; D013004:Somatostatin; D016291:Dizocilpine Maleate; D009020:Morphine; C016299:chelerythrine