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The Journal of Neurophysiology Vol. 82 No. 1 July 1999, pp. 272-282
Copyright ©1999 by the American Physiological Society
Department of Anatomy and Neurosciences and Marine Biomedical Institute, The University of Texas Medical Branch, Galveston, Texas 77555-1069
Neugebauer, Volker,
Ping-Sun Chen, and
William D. Willis.
Role of Metabotropic Glutamate Receptor Subtype mGluR1 in Brief
Nociception and Central Sensitization of Primate STT Cells. J. Neurophysiol. 82: 272-282, 1999.
G-protein coupled metabotropic glutamate receptors (mGluRs) are
important modulators of synaptic transmission in the mammalian CNS and
have been implicated in various forms of neuroplasticity and nervous
system disorders. Increasing evidence also suggests an involvement of
mGluRs in nociception and pain behavior although the contribution of
individual mGluR subtypes is not yet clear. Subtypes mGluR1 and mGluR5
are classified as group I mGluRs and share the ability to stimulate
phosphoinositide hydrolysis and activate protein kinase C. The present
study examined the role of group I mGluRs in nociceptive processing and
capsaicin-induced central sensitization of primate spinothalamic tract
(STT) cells in vivo. In 10 anesthetized male monkeys (Macaca
fascicularis) extracellular recordings were made from 20 STT
cells in the lumbar dorsal horn. Responses to brief (15 s) cutaneous
stimuli of innocuous (BRUSH) and barely and substantially noxious
(PRESS and PINCH, respectively) intensity were recorded before, during,
and after the infusion of group I mGluR agonists and antagonists into
the dorsal horn by microdialysis. Cumulative concentration-response relationships were obtained by applying different concentrations for at
least 20 min each (at 5 µl/min). The actual concentrations reached in
the tissue are 2-3 orders of magnitude lower than those in the
microdialysis fibers (values in this paper refer to the latter). The
group I antagonists were also applied at 10-25 min after capsaicin
injection. S-DHPG, a group I agonist at both mGluR1 and mGluR5,
potentiated the responses to innocuous and noxious stimuli (BRUSH > PRESS > PINCH) at low concentrations (10-100 µM;
n = 5) but had inhibitory effects at higher
concentrations (1-10 mM; n = 5). The mGluR5
agonist CHPG (1 µM-100 mM; n = 5) did not
potentiate but inhibited all responses (10-100 mM;
n = 5). AIDA (1 µM-100 mM), a mGluR1-selective
antagonist, dose-dependently depressed the responses to PINCH and PRESS
but not to BRUSH (n = 6). The group I (mGluR1 > mGluR5) antagonist CPCCOEt (1 µM-100 mM) had similar effects
(n = 6). Intradermal injections of capsaicin sensitized the STT cells to cutaneous mechanical stimuli. The enhancement of the responses by capsaicin resembled the potentiation by
the group I mGluR agonist S-DHPG (BRUSH > PRESS > PINCH).
CPCCOEt (1 mM) reversed the capsaicin-induced
sensitization when given as posttreatment (n = 5).
After washout of CPCCOEt, the sensitization resumed. Similarly, AIDA (1 mM; n = 7) reversed the capsaicin-induced sensitization and also blocked the potentiation by S-DHPG
(n = 5). These data suggest that the mGluR1 subtype
is activated endogenously during brief high-intensity cutaneous stimuli
(PRESS, PINCH) and is critically involved in capsaicin-induced central sensitization.
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