期刊
PAIN
卷 118, 期 1-2, 页码 145-154出版社
LIPPINCOTT WILLIAMS & WILKINS
DOI: 10.1016/j.pain.2005.08.004
关键词
intracellular Ca2+ stores; L-type VDCC; nociception; protein kinase C; rat (S)-3,5-DHPG
Activation of spinal group I metabotropic glutamate receptors (mGluRs) may have antinociceptive or pro-nociceptive effects in different pain models. Pharmacological activation of group I mGluRs leads to long-term depression (LTD) of synaptic strength between Ab-fibers and neurons in lamina 11 of spinal dorsal horn of the rat. Here, we studied the signal transduction pathways involved. Synaptic strength between A delta-fibers and lamina 11 neurons was assessed by perforated whole-cell patch-clamp recordings in a spinal cord-dorsal root slice preparation of young rats. Bath application of the specific group I mGluR agonist (S)-3,5-dihydroxyphenylglycine [(S)-3,5-DHPG] produced an LTD of A delta-fiber-evoked responses. LTD induction by (S)-3,5-DHPG was prevented, when intracellular Ca2+ stores were depleted by thapsigargin or cyclopiazonic acid (CPA). Preincubation with ryanodine to inhibit Ca2+-induced Ca2+ release had no effect on LTD-induction by (S)-3,5-DHPG. In contrast, pretreatment with 2-aminoethoxydiphenyl borate (2-APB), an inhibitor of inositol-1.4.5-tfisphosphate (IP3)-sensitive Ca2+ stores prevented LTD induction. Preincubation with the specific protein kinase C (PKC) inhibitors bisindolylmaleimide I (BIM) or cheterythrine, respectively, had no effect. Inhibition of L-type VDCCs by verapamil or nifedipine prevented LTD-induction by (S)-3,5-DHPG. The presently identified signal transduction cascade may be relevant to the long-term depression of sensory information in the spinal cord, including nociception. (c) 2005 International Association for the Study of Pain. Published by Elsevier B.V. All rights reserved.
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