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Volume 17, Number 3,
Issue of February 1, 1997
pp. 975-982
Copyright ©1997 Society for Neuroscience
Tumor Necrosis Factor Enhances the Capsaicin Sensitivity of Rat
Sensory Neurons
Received Oct. 31, 1996; accepted Nov. 18, 1996.
Grant D. Nicol1,
John
C. Lopshire2, and
Carl M. Pafford2
1 Department of Pharmacology and Toxicology and
2 Medical Neurobiology Program, School of Medicine, Indiana
University, Indianapolis, Indiana 46202-5120
The capacity of the proinflammatory cytokines, tumor necrosis
factor (TNF ) and interleukin 1 (IL-1 ), to modulate the sensitivity of isolated sensory neurons grown in culture to the excitatory chemical agent capsaicin was examined. Alterations in
capsaicin sensitivity were assessed by quantifying the number of
neurons labeled with cobalt after exposure to capsaicin and by
recording the whole-cell response from a single neuron to the focal
application of capsaicin. A 24 hr pretreatment of the neuronal cultures
with TNF (10 or 50 ng/ml), but not IL-1 (10 or 50 ng/ml), produced a concentration-dependent increase in the number of
cobalt-labeled neurons after exposure to 100 nM capsaicin.
The peak increase in the number of labeled neurons was attained after a
4 hr treatment with 10 ng/ml TNF . Similarly, pretreatment with
TNF (10 ng/ml for 4, 12, and 24 hr) produced a greater than twofold
increase in the average peak amplitude of the inward current evoked by 100 nM capsaicin. Both the TNF -induced increase in
labeling and current amplitude were blocked by treating the neuronal
cultures with indomethacin before the addition of TNF . Enhancement
of the capsaicin-evoked current also was blocked by the specific cyclo-oxygenase-2 inhibitor SC-236. These results indicate that TNF
can enhance the sensitivity of sensory neurons to the excitation produced by capsaicin and that this enhancement likely is mediated by
the neuronal production of prostaglandins. Isolated sensory neurons
grown in culture may prove to be a useful model system in which to
explore how prolonged exposure to mediators associated with chronic
inflammation alter the regulatory pathways that modulate the
excitability of the nervous system.
Key words:
tumor necrosis factor ;
interleukin 1 ;
capsaicin;
sensitization;
prostaglandins;
cyclo-oxygenase-2;
membrane
excitability
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