Is TRPV2 a receptor of painful heat? The knockouts say no.
The transient receptor potential channel TRPV1 is a sensor of painful heat in nociceptive neurons. But when TRPV1 is knocked out, animals are still able to respond to high temperatures, indicating that nociceptors harbor additional high heat receptors. Earlier this year, a team in Belgium and Germany reported evidence that a distantly related channel, TRPM3, shares heat-detecting duties with TRPV1 (Vriens et al., 2011; see PRF related news story).
Meanwhile, TRPV2 has been seen as another candidate receptor for noxious heat. Now, as reported by Park et al., the results from TRPV2 knockout mice are in. The findings argue that (at least in mice) TRPV2 is not a noxious heat sensor after all.
The study, from the lab of Michael Caterina at Johns Hopkins University School of Medicine in Baltimore, Maryland, shows that TRPV2 knockout mice, or TRPV1/TRPV2 double knockouts, had no problem sensing high temperatures—either in the basal state or in inflammatory or neuropathic conditions. The TRPV2 knockouts also were not impaired in their responses to mechanical stimuli. The knockout mice did have low perinatal viability, but those that survived to adulthood had pain responses that appeared to be perfectly normal. Electrophysiological recordings from skin afferents of wild-type and TRPV2 knockout mice were also similar.
Two other channels, TRPV3 and TRPV4, have also been proposed as possible heat sensors. However, in another recent paper, the Caterina lab showed that TRPV3 and TRPV4 knockout mice have fairly normal heat responses (Huang et al., 2011). That leaves TRPV1 and TRPM3 as likely noxious heat sensors. Data from the Vriens et al. TRPM3 study indicate that there are yet others to be discovered. So stay tuned.
Comments
Megan Talkington, Pain Research Forum
Is TRPV2 a receptor of painful heat? The knockouts say no.
The transient receptor potential channel TRPV1 is a sensor of painful heat in nociceptive neurons. But when TRPV1 is knocked out, animals are still able to respond to high temperatures, indicating that nociceptors harbor additional high heat receptors. Earlier this year, a team in Belgium and Germany reported evidence that a distantly related channel, TRPM3, shares heat-detecting duties with TRPV1 (Vriens et al., 2011; see PRF related news story).
Meanwhile, TRPV2 has been seen as another candidate receptor for noxious heat. Now, as reported by Park et al., the results from TRPV2 knockout mice are in. The findings argue that (at least in mice) TRPV2 is not a noxious heat sensor after all.
The study, from the lab of Michael Caterina at Johns Hopkins University School of Medicine in Baltimore, Maryland, shows that TRPV2 knockout mice, or TRPV1/TRPV2 double knockouts, had no problem sensing high temperatures—either in the basal state or in inflammatory or neuropathic conditions. The TRPV2 knockouts also were not impaired in their responses to mechanical stimuli. The knockout mice did have low perinatal viability, but those that survived to adulthood had pain responses that appeared to be perfectly normal. Electrophysiological recordings from skin afferents of wild-type and TRPV2 knockout mice were also similar.
Two other channels, TRPV3 and TRPV4, have also been proposed as possible heat sensors. However, in another recent paper, the Caterina lab showed that TRPV3 and TRPV4 knockout mice have fairly normal heat responses (Huang et al., 2011). That leaves TRPV1 and TRPM3 as likely noxious heat sensors. Data from the Vriens et al. TRPM3 study indicate that there are yet others to be discovered. So stay tuned.