Modulation of Sensory Neuron Mechanotransduction by PKC- and Nerve Growth Factor-Dependent Pathways

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 i...

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Bibliographic Details
Published in:Proceedings of the National Academy of Sciences - PNAS 2006-03, Vol.103 (12), p.4699-4704
Main Authors: Di Castro, Amalia, Drew, Liam J., Wood, John N., Cesare, Paolo
Format: Article
Language:English
Subjects:
Animals
Biological Sciences
Cell membranes
Cells, Cultured
Electrophysiology
Enzyme Activation - drug effects
Hyperalgesia
Ion channels
Ions
Mechanotransduction, Cellular
Nerve Growth Factor - pharmacology
Neurons
Neurons, Afferent - drug effects
Neurons, Afferent - metabolism
Neurons, Afferent - physiology
Neuroscience
Neurosciences
Nociceptors
Pain
Protein Kinase C - antagonists & inhibitors
Protein Kinase C - drug effects
Protein Kinase C - metabolism
Rats
Rats, Sprague-Dawley
Receptors
Sensitization
Sensory neurons
Signal transduction
Tetanus Toxin - pharmacology
Tetradecanoylphorbol Acetate - pharmacology
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Summary: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.
ISSN:0027-8424
1091-6490
DOI:10.1073/pnas.0508005103