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The Journal of Neurophysiology Vol. 81 No. 2 February 1999, pp. 575-583
Copyright ©1999 by the American Physiological Society
Schrier Research Laboratory, Departments of Psychology and Neuroscience, Brown University Providence, Rhode Island 02912
Cannabinoid suppression of noxious heat-evoked activity in wide dynamic
range neurons in the lumbar dorsal horn of the rat. The effects
of cannabinoid agonists on noxious heat-evoked firing of 62 spinal wide
dynamic range (WDR) neurons were examined in urethan-anesthetized rats
(1 cell/animal). Noxious thermal stimulation was applied with a Peltier
device to the receptive fields in the ipsilateral hindpaw of isolated
WDR neurons. To assess the site of action, cannabinoids were
administered systemically in intact and spinally transected rats and
intraventricularly. Both the aminoalkylindole cannabinoid WIN55,212-2
(125 µg/kg iv) and the bicyclic cannabinoid CP55,940 (125 µg/kg iv)
suppressed noxious heat-evoked activity. Responses evoked by mild
pressure in nonnociceptive neurons were not altered by CP55,940 (125 µg/kg iv), consistent with previous observations with another
cannabinoid agonist, WIN55,212-2. The cannabinoid induced-suppression
of noxious heat-evoked activity was blocked by pretreatment with
SR141716A (1 mg/kg iv), a competitive antagonist for central
cannabinoid CB1 receptors. By contrast, intravenous administration of
either vehicle or the receptor-inactive enantiomer WIN55,212-3 (125 µg/kg) failed to alter noxious heat-evoked activity. The suppression
of noxious heat-evoked activity induced by WIN55,212-2 in the lumbar
dorsal horn of intact animals was markedly attenuated in spinal rats.
Moreover, intraventricular administration of WIN55,212-2 suppressed
noxious heat-evoked activity in spinal WDR neurons. By contrast, both
vehicle and enantiomer were inactive. These findings suggest that
cannabinoids selectively modulate the activity of nociceptive neurons
in the spinal dorsal horn by actions at CB1 receptors. This modulation
represents a suppression of pain neurotransmission because the
inhibitory effects are selective for pain-sensitive neurons and are
observed with different modalities of noxious stimulation. The data
also provide converging lines of evidence for a role for descending
antinociceptive mechanisms in cannabinoid modulation of spinal
nociceptive processing.
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