title: Protein kinase C inhibitor chelerythrine attenuates the morphine-induced excitatory amino acid release and reduction of the antinociceptive effect of morphine in rats injected intrathecally with pertussis toxin.
abstract: Neuropathic pain syndromes respond poorly to opioid treatment. In our previous studies, we found that intrathecal (i.t.) injection of pertussis toxin (PTX) produces thermal hyperalgesia, which is poorly responsive to morphine and is accompanied by an increase in cerebrospinal fluid (CSF) levels of excitatory amino acids (EAAs) and protein kinase C (PKC) activation. In the present study, rats were implanted with an i.t. catheter for drug injection and a microdialysis probe for CSF dialysate collection. On the fourth day after injection of PTX (2 microg, i.t.), there was a significant reduction in the antinociceptive effect of morphine (10 microg, i.t.) which was accompanied by an increase in levels of EAAs. Pretreatment with the PKC inhibitor, chelerythrine (25 microg, i.t.) one hour before morphine injection markedly inhibited both effects. These results suggest that, in PTX-treated rats, PKC plays an important role in inhibiting the morphine-induced spinal EAA release, which might be related to the reduced antinociceptive effect of morphine.
authors.affiliation: Department of Anesthesiology, Shin Kong Wu Ho-Su memorial Hospital, Taipei, Taiwan.
authors.forename: Gong-Jhe
authors.initials: GJ
authors.lastname: Wu
authors.forename: Zhi-Hong
authors.initials: ZH
authors.lastname: Wen
authors.forename: Yi-Chen
authors.initials: YC
authors.lastname: Chang
authors.forename: San-Nan
authors.initials: SN
authors.lastname: Yang
authors.forename: Pao-Luh
authors.initials: PL
authors.lastname: Tao
authors.forename: Chih-Shung
authors.initials: CS
authors.lastname: Wong
mesh_terms: D000470:Alkaloids; D000701:Analgesics, Opioid / Q000494:pharmacology*; D000818:Animals; D053119:Benzophenanthridines; D004791:Enzyme Inhibitors / Q000494:pharmacology*; D018846:Excitatory Amino Acids / Q000134:cerebrospinal fluid*; D007278:Injections, Spinal; D008297:Male; D009020:Morphine / Q000494:pharmacology*; D037342:Pertussis Toxin / Q000008:administration & dosage*; D010617:Phenanthridines / Q000494:pharmacology*; D011493:Protein Kinase C / Q000037:antagonists & inhibitors*; D051381:Rats; D017208:Rats, Wistar
chemical_list: D000470:Alkaloids; D000701:Analgesics, Opioid; D053119:Benzophenanthridines; D004791:Enzyme Inhibitors; D018846:Excitatory Amino Acids; D010617:Phenanthridines; D009020:Morphine; C016299:chelerythrine; D037342:Pertussis Toxin; D011493:Protein Kinase C