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Modulation of Sensory Neuron Mechanotransduction by PKC- and Nerve Growth Factor-Dependent Pathways
Amalia Di Castro, Liam J. Drew, John N. Wood and Paolo Cesare
Proceedings of the National Academy of Sciences of the United States of America
Vol. 103, No. 12 (Mar. 21, 2006), pp. 4699-4704
Published by: National Academy of Sciences
Stable URL: http://www.jstor.org/stable/30049004
Page Count: 6
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Many sensations of pain are evoked by mechanical stimuli, and in inflammatory conditions, sensitivity to such stimuli is commonly increased. Here we used cultured sensory neurons as a model of the peripheral terminal to investigate the effects of inflammatory signaling pathways on mechanosensitive ion channels. Activation of two of these pathways enhanced transduction in a major population of nociceptors. The proinflammatory neurotrophin nerve growth factor caused an up-regulation of mechanically activated currents via a transcriptional mechanism. Activators of PKC, given in vitro and in vivo, also caused an increase in mechanically activated membrane current and behavioral sensitization to mechanical stimulation, respectively. The effect of activating PKC was inhibited by tetanus toxin, suggesting that insertion of new channels into the cell membrane is involved in sensitization. These results reveal previously undescribed mechanisms by which PKC and nerve growth factor synergistically enhance the response of nociceptors to mechanical stimuli, suggesting possible targets for pain treatment.
Proceedings of the National Academy of Sciences of the United States of America © 2006 National Academy of Sciences