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

Gong-Jhe Wu, Zhi Hong Wen, Yi Chen Chang, San Nan Yang, Pao Luh Tao, Chih Shung Wong

Research output: Contribution to journalArticle

5 Citations (Scopus)

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 μg, i.t.), there was a significant reduction in the antinociceptive effect of morphine (10 μg, i.t.) which was accompanied by an increase in levels of EAAs. Pretreatment with the PKC inhibitor, chelerythrine (25 μg, 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.

Original languageEnglish
Pages (from-to)1801-1807
Number of pages7
JournalLife Sciences
Volume78
Issue number16
DOIs
Publication statusPublished - Mar 13 2006
Externally publishedYes

Keywords

  • Excitatory amino acids
  • Morphine
  • Pertussis toxin
  • Protein kinase C

ASJC Scopus subject areas

  • Pharmacology

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