RESEARCH ARTICLE


Sensitisation of Nociceptors – What are Ion Channels Doing?



Michael J.M. Fischer*, Stephanie W.Y. Mak, Peter A. McNaughton
Department of Pharmacology, University of Cambridge, UK.


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Creative Commons License
© 2010 Fischer et al.

open-access license: This is an open access article distributed under the terms of the Creative Commons Attribution 4.0 International Public License (CC-BY 4.0), a copy of which is available at: https://creativecommons.org/licenses/by/4.0/legalcode. This license permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.

* Address correspondence to this author at the Department of Pharmacology, University of Cambridge, UK; Fax: +44 1223 334100; E-mail: mjmf2@cam.ac.uk


Abstract

Nociceptors are peripheral sensory neurones which respond to painful (noxious) stimuli. The terminals of nociceptors, which have a high threshold to stimulation in their native state, undergo a process known as sensitisation, or lowering of threshold, following injury or inflammation. Amongst sensory receptors, sensitisation is a property unique to nociceptors. A shift in the stimulus-response function of nociceptors renders them more sensitive, resulting in both a reduction in the activation threshold, such that previously non-noxious stimuli are perceived as noxious (allodynia) and an increased response to suprathreshold stimuli (hyperalgesia). Sensitisation protects us from harm and is essential for survival, but it can be disabling in conditions of chronic inflammation. This review focuses on three stages in sensitisation: 1) Inflammatory mediators, which are released from damaged resident cells and from others that invade in response to inflammation, and include bradykinin, prostaglandins, serotonin, low pH, ATP, neurotrophins, nitric oxide and cytokines; 2) Intracellular signalling molecules which are important in transmitting the actions of inflammatory mediators and include protein kinase A and C, Src kinase, mitogen-activated protein kinases and the membrane lipid PIP2; and 3) Ion channel targets of intracellular signalling which ultimately cause sensitisation and include the temperaturesensitive transient receptor potential channels, acid-sensitive ion channels, purinoceptor-gated channels, and the voltagesensitive sodium, potassium, calcium and HCN channels.

Keywords: Pain, Hyperalgesia, Inflammation, Cell Signalling.