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Warm-coding deficits and aberrant inflammatory pain in mice lacking P2X3 receptors

A Corrigendum to this article was published on 08 February 2001

Abstract

ATP activates damage-sensing neurons (nociceptors) and can evoke a sensation of pain1. The ATP receptor P2X3 is selectively expressed by nociceptors2,3 and is one of seven ATP-gated, cation-selective ion channels4,5,6. Here we demonstrate that ablation of the P2X3 gene results in the loss of rapidly desensitizing ATP-gated cation currents in dorsal root ganglion neurons, and that the responses of nodose ganglion neurons to ATP show altered kinetics and pharmacology resulting from the loss of expression of P2X2/3 heteromultimers. Null mutants have normal sensorimotor function. Behavioural responses to noxious mechanical and thermal stimuli are also normal, although formalin-induced pain behaviour is reduced. In contrast, deletion of the P2X3 receptor causes enhanced thermal hyperalgesia in chronic inflammation. Notably, although dorsal-horn neuronal responses to mechanical and noxious heat application are normal, P2X3-null mice are unable to code the intensity of non-noxious ‘warming’ stimuli.

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Figure 1: Physiological effects of deleting the P2X3 receptor.
Figure 2: Behavioural effects of deleting the P2X3 receptor.

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Acknowledgements

We thank the Wellcome Trust, EC Biomed and the MRC for support and H. Thompson for help with genotyping mice.

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Correspondence to John N. Wood.

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Souslova, V., Cesare, P., Ding, Y. et al. Warm-coding deficits and aberrant inflammatory pain in mice lacking P2X3 receptors. Nature 407, 1015–1017 (2000). https://doi.org/10.1038/35039526

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