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Sodium channels and nociceptive nerve endings

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Sodium Channels, Pain, and Analgesia

Part of the book series: Progress in Inflammation Research ((PIR))

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Conclusion

Both C and Aδ nociceptive neurones express multiple subtypes of Na+ channel. In particular, TTX-resistant Na+ channels appear to play an important role in determining the behaviour of these neurones. Present evidence suggests that initiation of nerve impulses in the sensory nerve terminals of nociceptors is dependent on the activation of TTX-resistant channels. Furthermore, the voltage dependence and kinetics of these Na+ channels may, at least in part, explain why these receptors have high sensory thresholds. In accord with this idea, a range of hyperalgesic agents released in inflamed tissue have been demonstrated to modify the behaviour of Na+ current attributed to Nav1.8 channels in a manner that will lower the voltage threshold for initiating action potentials. However, this action of hyperalgesic agents is likely to be only one of a range of mechanisms that contribute to inflammatory pain. For example, increased expression of both TTX-sensitive and TTX-resistant Na+ channels may also contribute to lowering the voltage threshold and changing the firing characteristics of nociceptive nerve endings.

Based on current evidence, selective blockade of Na+ channel subtypes, in particular Nav1.8 and/or Nav1.9, may prove useful in controlling painful signals arising from damaged tissue without interfering with other neural functions. Blockade of these channel subtypes may also prove useful in inhibiting neurogenic inflammation of local origin.

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  1. Prince of Wales Medical Research Institute, Barker St, Randwick, Sydney, NSW 2031, Australia

    James A. Brock

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Editors and Affiliations

  1. PLIVA Research Institute Ltd., Prilaz baruna Filipovića 29, HR-10000, Zagreb, Croatia

    Michael J. Parnham PhD (Senior Scientific Advisor) (Senior Scientific Advisor)

  2. Department of Pharmacology, University of Oxford, Mansfield Road, Oxford, OX1 3QT, UK

    Kevin Coward

  3. Molecular Nociception Group Department of Biology Medawar Building, University College London, Gower Street, London, WC1E 6BT, UK

    Mark D. Baker

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Brock, J.A. (2005). Sodium channels and nociceptive nerve endings. In: Parnham, M.J., Coward, K., Baker, M.D. (eds) Sodium Channels, Pain, and Analgesia. Progress in Inflammation Research. Birkhäuser Basel. https://doi.org/10.1007/3-7643-7411-X_5

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