Leading science, pioneering therapies
CRM Publications

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

TitleWarm-coding deficits and aberrant inflammatory pain in mice lacking P2X3 receptors.
Publication TypeJournal Article
Year of Publication2000
AuthorsSouslova V, Cesare P, Ding Y, Akopian AN, Stanfa L, Suzuki R, Carpenter K, Dickenson A, Boyce S, Hill R, Nebenuis-Oosthuizen D, Smith AG, Kidd EJ, Wood JN
JournalNature
Volume407
Issue6807
Pagination1015-7
Date Published2000 Oct 26
ISSN0028-0836
KeywordsAdenosine Triphosphate, Animals, Body Temperature, Cells, Cultured, Ganglia, Spinal, Hot Temperature, Hyperalgesia, Inflammation, Mice, Mice, Inbred C57BL, Motor Skills, Neurons, Nociceptors, Nodose Ganglion, Posterior Horn Cells, Receptors, Purinergic P2, Receptors, Purinergic P2X3
Abstract

ATP activates damage-sensing neurons (nociceptors) and can evoke a sensation of pain. The ATP receptor P2X3 is selectively expressed by nociceptors and is one of seven ATP-gated, cation-selective ion channels. 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 P2X(2/3) 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.

DOI10.1038/35039526
Alternate JournalNature
PubMed ID11069182