Tumor necrosis factor enhances the capsaicin sensitivity of rat sensory neurons

Grant D. Nicol, John C. Lopshire, Carl M. Pafford

Research output: Contribution to journalArticle

121 Scopus citations

Abstract

The capacity of the proinflammatory cytokines, tumor necrosis factor a (TNFα) and interleukin 1β (IL-1β), 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 TNFα (10 or 50 ng/ml), but not IL-1β (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 TNFα. Similarly, pretreatment with TNFα (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 TNFα-induced increase in labeling and current amplitude were blocked by treating the neuronal cultures with indomethacin before the addition of TNFα. Enhancement of the capsaicin- evoked current also was blocked by the specific cyclo-oxygenase-2 inhibitor SC-236. These results indicate that TNFα 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.

Original languageEnglish (US)
Pages (from-to)975-982
Number of pages8
JournalJournal of Neuroscience
Volume17
Issue number3
StatePublished - Feb 1 1997

Keywords

  • capsaicin
  • cyclo-oxygenase-2
  • interleukin 1β
  • membrane excitability
  • prostaglandins
  • sensitization
  • tumor necrosis factor α

ASJC Scopus subject areas

  • Neuroscience(all)

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