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

doi:10.1016/j.lfs.2005.08.020

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 journal › Article › peer-review

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 language	English
Pages (from-to)	1801-1807
Number of pages	7
Journal	Life Sciences
Volume	78
Issue number	16
DOIs	https://doi.org/10.1016/j.lfs.2005.08.020
Publication status	Published - Mar 13 2006
Externally published	Yes

Keywords

Excitatory amino acids
Morphine
Pertussis toxin
Protein kinase C

ASJC Scopus subject areas

General Pharmacology, Toxicology and Pharmaceutics
General Biochemistry,Genetics and Molecular Biology

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Wu, G.-J., Wen, Z. H., Chang, Y. C., Yang, S. N., Tao, P. L., & Wong, C. S. (2006). 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. Life Sciences, 78(16), 1801-1807. https://doi.org/10.1016/j.lfs.2005.08.020

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. / Wu, Gong-Jhe; Wen, Zhi Hong; Chang, Yi Chen et al.
In: Life Sciences, Vol. 78, No. 16, 13.03.2006, p. 1801-1807.

Research output: Contribution to journal › Article › peer-review

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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 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.",

keywords = "Excitatory amino acids, Morphine, Pertussis toxin, Protein kinase C",

author = "Gong-Jhe Wu and Wen, {Zhi Hong} and Chang, {Yi Chen} and Yang, {San Nan} and Tao, {Pao Luh} and Wong, {Chih Shung}",

note = "Funding Information: This work was supported by grants from the National Science Council (NSC 94-2314-B-016-002) and the National Health Research Institute (NHRI-EX94-9401-NP) of Taiwan.",

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AU - Wen, Zhi Hong

AU - Chang, Yi Chen

AU - Yang, San Nan

AU - Tao, Pao Luh

AU - Wong, Chih Shung

N1 - Funding Information: This work was supported by grants from the National Science Council (NSC 94-2314-B-016-002) and the National Health Research Institute (NHRI-EX94-9401-NP) of Taiwan.

PY - 2006/3/13

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N2 - 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.

AB - 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.

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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

Keywords

ASJC Scopus subject areas

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