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PMID: 8622132 Published · ppublish English Journal Article Research Support, U.S. Gov't, P.H.S.

Possible role of protein kinase C in the sensitization of primate spinothalamic tract neurons.

Lin Q, Peng YB, Willis WD

Abstract

The responsiveness of spinal cord nociceptive neurons to innocuous mechanical stimuli can be increased by the release of excitatory amino acids (EAAs) and peptides attributable to an injury-induced barrage of impulses. This sensitization of spinal dorsal horn neurons can also result from administration of phorbol ester by microdialysis, presumably by direct activation of protein kinase C (PKC). This study was designed to examine the effects of central sensitization of spinothalamic tract (STT) neurons produced by intradermal injection of capsaicin on the descending inhibition driven from the periaqueductal gray (PAG) and the possible role of PKC in this process in anesthetized monkeys. Sensitization of responses of STT cells to mechanical stimuli was induced by intradermal injection of capsaicin. PAG inhibition was significantly attenuated when sensitization of responses to mechanical stimuli occurred. However, perfusion of the spinal cord with NPC15437 (a selective PKC inhibitor) by microdialysis could prevent the sensitization of the responses to mechanical stimuli and the reduction in PAG inhibition of these responses induced by capsaicin injection. Results similar to those produced by capsaicin injection were observed when a PKC activator, phorbol ester (12-O-tetradecanoylphorbol-13-acetate), was infused within the dorsal horn by microdialysis. An inactive phorbol ester (4 alpha-phorbol 12,13-didecanoate) had no effect. These results provide evidence that the activation of PKC contributes to the development of central sensitization in dorsal horn neurons produced by chemical stimulation with capsaicin. Attenuation of the effectiveness of PAG inhibition takes place when the sensitization of dorsal horn cells develops, and PKC may play a significant role in this process.

MeSH Terms
Animals Capsaicin/pharmacology Female Injections, Intradermal Macaca fascicularis Male Neural Inhibition/drug effects Neurons/drug effects,physiology Periaqueductal Gray/physiology Physical Stimulation Piperidines/pharmacology Protein Kinase C/antagonists & inhibitors,physiology Spinothalamic Tracts/cytology,drug effects,physiology Tetradecanoylphorbol Acetate/pharmacology
Chemicals
Piperidines NPC 15437 Protein Kinase C Tetradecanoylphorbol Acetate Capsaicin
Authors & Affiliations
3 authors, click to expand affiliations / ORCID
Lin Q
Department of Anatomy and Neurosciences, Marine Biomedical Institute, University of Texas Medical Branch, Galveston, 77555-1069, USA.
Peng Y B
Willis W D
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Article Info
Journal
The Journal of neuroscience : the official journal of the Society for Neuroscience
Abbr.
J Neurosci
ISSN
0270-6474
Published
1996-05-01
Pages
3026-34
Language
English
Region
United States
NLM ID
8102140
PMCID
PMC6579049
Subset
IM
Grants
NINDS NIH HHS · P01 NS011255 · United States
NINDS NIH HHS · R01 NS009743 · United States
NINDS NIH HHS · NS09743 · United States
NINDS NIH HHS · NS11255 · United States
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