Warm-coding deficits and aberrant inflammatory pain in mice lacking P2X3 receptors.
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.
Souslova
V
V
Department of Biology, University College London, UK.
Cesare
P
P
Ding
Y
Y
Akopian
A N
AN
Stanfa
L
L
Suzuki
R
R
Carpenter
K
K
Dickenson
A
A
Boyce
S
S
Hill
R
R
Nebenuis-Oosthuizen
D
D
Smith
A J
AJ
Kidd
E J
EJ
Wood
J N
JN
D000255:Adenosine Triphosphate / Q000502:physiology; D000818:Animals; D001831:Body Temperature; D002478:Cells, Cultured; D005727:Ganglia, Spinal / Q000166:cytology / Q000502:physiology; D006358:Hot Temperature; D006930:Hyperalgesia / Q000209:etiology; D007249:Inflammation / Q000209:etiology; D051379:Mice; D008810:Mice, Inbred C57BL; D009048:Motor Skills; D009474:Neurons / Q000502:physiology; D009619:Nociceptors / Q000502:physiology*; D009620:Nodose Ganglion / Q000166:cytology / Q000502:physiology; D020671:Posterior Horn Cells / Q000502:physiology; D018048:Receptors, Purinergic P2 / Q000235:genetics / Q000502:physiology*; D058477:Receptors, Purinergic P2X3
C546409:P2rx3 protein, mouse; D018048:Receptors, Purinergic P2; D058477:Receptors, Purinergic P2X3; D000255:Adenosine Triphosphate