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.
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.
Wu
Gong-Jhe
GJ
Department of Anesthesiology, Shin Kong Wu Ho-Su memorial Hospital, Taipei, Taiwan.
Wen
Zhi-Hong
ZH
Chang
Yi-Chen
YC
Yang
San-Nan
SN
Tao
Pao-Luh
PL
Wong
Chih-Shung
CS
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
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