TY - JOUR
T1 - Enhanced thermal avoidance in mice lacking the ATP receptor P2X3
AU - Shimizu, Isao
AU - Iida, Tohko
AU - Guan, Yun
AU - Zhao, Chengshui
AU - Raja, Srinivasa N.
AU - Jarvis, Michael F.
AU - Cockayne, Debra A.
AU - Caterina, Michael J.
N1 - Funding Information:
We thank Juan Wang for expert technical assistance, William Wright and James Abbott for help with design and construction of thermal gradient devices, and members of the Caterina Lab for helpful suggestions. Supported by The American Cancer Society Research Scholars Grant RGS-01-063-01-CSM and awards from the W.M. Keck Foundation, Searle Scholars Program, and Arnold and Mabel Beckman Foundation to M.J.C.
Copyright:
Copyright 2008 Elsevier B.V., All rights reserved.
PY - 2005/7
Y1 - 2005/7
N2 - 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.
AB - 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.
KW - P2X
KW - P2X
KW - TRPV1
KW - Temperature
KW - Thermosensation
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U2 - 10.1016/j.pain.2005.03.030
DO - 10.1016/j.pain.2005.03.030
M3 - Article
C2 - 15927378
AN - SCOPUS:20444484395
SN - 0304-3959
VL - 116
SP - 96
EP - 108
JO - Pain
JF - Pain
IS - 1-2
ER -