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The Journal of Neurophysiology Vol. 82 No. 6 December 1999, pp. 3046-3055
Copyright ©1999 by the American Physiological Society
Section of Neurobiology, Physiology and Behavior, University of California, Davis, California 95616
Jinks, Steven L. and
E. Carstens.
Activation of Spinal Wide Dynamic Range Neurons by Intracutaneous
Microinjection of Nicotine. J. Neurophysiol. 82: 3046-3055, 1999. Nicotine evokes pain in the skin
and oral mucosa and excites a subpopulation of cutaneous nociceptors,
but little is known about the central transmission of chemogenic pain.
We have investigated the responses of lumbar spinal wide dynamic range
(WDR)-type dorsal horn neurons to intracutaneous (ic) microinjection of
nicotine in pentobarbital-anesthetized rats. Nearly all (97%) units
responded to nicotine microinjected ic (1 µl) into the low-threshold
region of the hind-paw mechanosensitive receptive field in a
concentration-related manner (0.01-10%). Responses to repeated
injections of 10% nicotine exhibited tachyphylaxis at 5-, 10-, and
15-min interstimulus intervals. Significant tachyphylaxis was not seen
with 1% nicotine. All nicotine-responsive units tested
(n = 30) also responded to ic histamine (1 µl,
3%) and did not exhibit tachyphylaxis to repeated histamine. However, there was significant cross-tachyphylaxis of nicotine to histamine. Thus 5 min after ic nicotine, histamine-evoked responses were attenuated significantly compared with the initial histamine-evoked response prior to nicotine, with partial recovery over the ensuing 15 min. Neuronal excitation by ic nicotine was not mediated by histamine
H1 receptors because ic injection of the H1 receptor antagonist,
cetirizine, had no effect on ic nicotine-evoked responses, whereas it
significantly attenuated ic histamine-evoked responses in the same
neurons. The lowest-threshold portion of cutaneous receptive fields
showed a significant expansion in area at 20 min after ic nicotine
10%, indicative of sensitization. Responses to 1% nicotine were
significantly reduced after ic injection of the nicotinic antagonist,
mecamylamine (0.1% ic), with no recovery over the ensuing 40-60 min.
These data indicate that nicotine ic excites spinal WDR neurons, partly
via neuronal nicotinic acetylcholine receptors that are presumably
expressed in cutaneous nociceptor terminals. Repeated injections of
high concentrations of nicotine led to tachyphylaxis and
cross-tachyphylaxis with histamine, possibly relevant to peripheral
analgesic effects of nicotine.
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