title: Enhanced thermal avoidance in mice lacking the ATP receptor P2X3.
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 degrees 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.
authors.affiliation: Department of Biological Chemistry, Johns Hopkins School of Medicine, 408 Biophysics Building, 725 North Wolfe Street, Baltimore, MD 21205, USA.
authors.forename: Isao
authors.initials: I
authors.lastname: Shimizu
authors.forename: Tohko
authors.initials: T
authors.lastname: Iida
authors.forename: Yun
authors.initials: Y
authors.lastname: Guan
authors.forename: Chengshui
authors.initials: C
authors.lastname: Zhao
authors.forename: Srinivasa N
authors.initials: SN
authors.lastname: Raja
authors.forename: Michael F
authors.initials: MF
authors.lastname: Jarvis
authors.forename: Debra A
authors.initials: DA
authors.lastname: Cockayne
authors.forename: Michael J
authors.initials: MJ
authors.lastname: Caterina
mesh_terms: D000704:Analysis of Variance; D000818:Animals; D001522:Behavior, Animal; D001831:Body Temperature / Q000502:physiology; D002118:Calcium / Q000378:metabolism; D002452:Cell Count / Q000379:methods; D002478:Cells, Cultured; D003952:Diagnostic Imaging; D004307:Dose-Response Relationship, Radiation; D004924:Escape Reaction / Q000187:drug effects / Q000502:physiology*; D005786:Gene Expression Regulation / Q000528:radiation effects; D006358:Hot Temperature; D006930:Hyperalgesia / Q000235:genetics / Q000503:physiopathology*; D007150:Immunohistochemistry / Q000379:methods; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout / Q000502:physiology*; D009475:Neurons, Afferent / Q000502:physiology; D016761:Oncogene Proteins v-fos / Q000378:metabolism; D010147:Pain Measurement; D010636:Phenols / Q000008:administration & dosage; D010812:Physical Stimulation / Q000379:methods; D011083:Polycyclic Compounds / Q000008:administration & dosage; D018048:Receptors, Purinergic P2 / Q000172:deficiency* / Q000502:physiology; D058477:Receptors, Purinergic P2X3; D013116:Spinal Cord / Q000166:cytology / Q000502:physiology; D013697:Thermosensing / Q000187:drug effects / Q000502:physiology*; D013997:Time Factors
chemical_list: C470346:A-317491; D016761:Oncogene Proteins v-fos; C546409:P2rx3 protein, mouse; D010636:Phenols; D011083:Polycyclic Compounds; D018048:Receptors, Purinergic P2; D058477:Receptors, Purinergic P2X3; D002118:Calcium