Enhanced thermal avoidance in mice lacking the ATP receptor P2X3

Isao Shimizu, Tohko Iida, Yun Guan, Chengshui Zhao, Srinivasa Naga Raja, Michael F. Jarvis, Debra A. Cockayne, Michael Caterina

Research output: Contribution to journalArticle

Abstract

P2X3 is an ATP-gated cation channel subtype expressed by a subpopulation of primary sensory neurons. In vivo spinal cord recordings in mice lacking P2X3 (P2X3-/-) have suggested that this protein may be important for the coding of peripheral warm stimuli. To explore this possibility more thoroughly, we examined behavioral and electrophysiological responses to thermal stimuli in P2X3 -/- mice. As previously reported, recording from the spinal cord dorsal horn of anesthetized P2X3-/- mice revealed a blunted response of wide dynamic range neurons to hind paw heating. When placed in a thermal gradient, however, P2X3-/- mice exhibited an unexpectedly enhanced avoidance of both hot and cold temperatures, relative to controls. In the tail immersion test, mutant mice exhibited shorter withdrawal latencies at temperatures above and below thermoneutrality. Consistent with these changes, P2X3-/- mice exhibited enhanced induction of spinal cord c-FOS following hind paw heating to 45°C. Thus, gain- and loss-of-function thermosensory phenotypes coexist in P2X3 -/- mice. No changes in thermal preference were observed in wild-type mice injected subcutaneously with the P2X3 antagonist, A317491 or intrathecally with the P2X3 and P2X1 antagonist TNP-ATP. The reason for this apparent discrepancy is unclear, but we cannot exclude the possibility that compensatory events contribute, at least in part, to the P2X3-/- phenotype. Regardless, this study illustrates the utility of thermal preference assays as part of a comprehensive approach to the analysis of mouse thermosensation.

Original languageEnglish (US)
Pages (from-to)96-108
Number of pages13
JournalPain
Volume116
Issue number1-2
DOIs
StatePublished - Jul 2005

Fingerprint

Purinergic P2 Receptors
Hot Temperature
Heating
Spinal Cord
Phenotype
Taxis Response
Immersion
Sensory Receptor Cells
Cations
Tail
Adenosine Triphosphate
Neurons
Temperature

Keywords

  • P2X
  • P2X
  • Temperature
  • Thermosensation
  • TRPV1

ASJC Scopus subject areas

  • Clinical Neurology
  • Psychiatry and Mental health
  • Neurology
  • Neuroscience(all)
  • Pharmacology
  • Clinical Psychology

Cite this

Enhanced thermal avoidance in mice lacking the ATP receptor P2X3. / Shimizu, Isao; Iida, Tohko; Guan, Yun; Zhao, Chengshui; Raja, Srinivasa Naga; Jarvis, Michael F.; Cockayne, Debra A.; Caterina, Michael.

In: Pain, Vol. 116, No. 1-2, 07.2005, p. 96-108.

Research output: Contribution to journalArticle

Shimizu, I, Iida, T, Guan, Y, Zhao, C, Raja, SN, Jarvis, MF, Cockayne, DA & Caterina, M 2005, 'Enhanced thermal avoidance in mice lacking the ATP receptor P2X3', Pain, vol. 116, no. 1-2, pp. 96-108. https://doi.org/10.1016/j.pain.2005.03.030
Shimizu, Isao ; Iida, Tohko ; Guan, Yun ; Zhao, Chengshui ; Raja, Srinivasa Naga ; Jarvis, Michael F. ; Cockayne, Debra A. ; Caterina, Michael. / Enhanced thermal avoidance in mice lacking the ATP receptor P2X3. In: Pain. 2005 ; Vol. 116, No. 1-2. pp. 96-108.
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