title: TRP vanilloid 2 knock-out mice are susceptible to perinatal lethality but display normal thermal and mechanical nociception.
abstract: TRP vanilloid 2 (TRPV2) is a nonselective cation channel expressed prominently in medium- to large-diameter sensory neurons that can be activated by extreme heat (>52°C). These features suggest that TRPV2 might be a transducer of noxious heat in vivo. TRPV2 can also be activated by hypoosmolarity or cell stretch, suggesting potential roles in mechanotransduction. To address the physiological functions of TRPV2 in somatosensation, we generated TRPV2 knock-out mice and examined their behavioral and electrophysiological responses to heat and mechanical stimuli. TRPV2 knock-out mice showed reduced embryonic weight and perinatal viability. As adults, surviving knock-out mice also exhibited a slightly reduced body weight. TRPV2 knock-out mice showed normal behavioral responses to noxious heat over a broad range of temperatures and normal responses to punctate mechanical stimuli, both in the basal state and under hyperalgesic conditions such as peripheral inflammation and L5 spinal nerve ligation. Moreover, behavioral assays of TRPV1/TRPV2 double knock-out mice or of TRPV2 knock-out mice treated with resiniferatoxin to desensitize TRPV1-expressing afferents revealed no thermosensory consequences of TRPV2 absence. In line with behavioral findings, electrophysiological recordings from skin afferents showed that C-fiber responses to heat and C- and Aδ-fiber responses to noxious mechanical stimuli were unimpaired in the absence of TRPV2. The prevalence of thermosensitive Aδ-fibers was too low to permit comparison between genotypes. Thus, TRPV2 is important for perinatal viability but is not essential for heat or mechanical nociception or hypersensitivity in the adult mouse.
authors.affiliation: Department of Biological Chemistry, Center for Sensory Biology, Johns Hopkins University School of Medicine, Baltimore, Maryland 21205, USA.
authors.forename: Una
authors.initials: U
authors.lastname: Park
authors.forename: Nisha
authors.initials: N
authors.lastname: Vastani
authors.forename: Yun
authors.initials: Y
authors.lastname: Guan
authors.forename: Srinivasa N
authors.initials: SN
authors.lastname: Raja
authors.forename: Martin
authors.initials: M
authors.lastname: Koltzenburg
authors.forename: Michael J
authors.initials: MJ
authors.lastname: Caterina
mesh_terms: D000818:Animals; D000831:Animals, Newborn; D015220:Calcium Channels / Q000172:deficiency* / Q000235:genetics* / Q000502:physiology; D005260:Female; D020022:Genetic Predisposition to Disease / Q000235:genetics*; D006358:Hot Temperature / Q000009:adverse effects; D008297:Male; D008465:Mechanoreceptors / Q000502:physiology; D051379:Mice; D057507:Mice, 129 Strain; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D010147:Pain Measurement / Q000379:methods*; D010812:Physical Stimulation / Q000379:methods; D011247:Pregnancy; D011297:Prenatal Exposure Delayed Effects / Q000235:genetics / Q000378:metabolism; D011897:Random Allocation; D050916:TRPV Cation Channels / Q000172:deficiency* / Q000235:genetics* / Q000502:physiology
chemical_list: D015220:Calcium Channels; D050916:TRPV Cation Channels; C485717:Trpv2 protein, mouse