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Volume 16, Number 9,
Issue of May 1, 1996
pp. 3026-3034
Copyright ©1996 Society for Neuroscience
Possible Role of Protein Kinase C in the Sensitization of Primate
Spinothalamic Tract Neurons
Received Sept. 6, 1995; revised Jan. 23, 1996; accepted Feb. 9, 1996.
Qing Lin,
Yuan Bo Peng, and
William D. Willis
Department of Anatomy and Neurosciences, Marine Biomedical
Institute, University of Texas Medical Branch, Galveston, Texas
77555-1069
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 -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.
Key words:
protein kinase C;
periaqueductal gray;
spinothalamic
tract neurons;
capsaicin;
antinociception;
spinal cord;
monkey
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