AI Summary
This article discusses how the development of analgesics targeting TRPV1 receptors has been hindered by effects on core body temperature. The authors suggest that there are biased allosteric mechanisms involved in TRPV1 coupling to nociception and core body temperature regulation, which could be targeted to develop non-opioid analgesics without affecting core body temperature. This research has implications for the development of more effective pain medications that do not have unwanted side effects on body temperature.
Development of analgesics targeting TRPV1 receptors has been hampered by undesirable hypo- or hyperthermic effects induced by TRPV1 agonists/antagonists. Huang et al. suggest that biased allosteric mechanisms exist for TRPV1 coupling to nociception and CBT regulation, which may be selectively targeted for developing non-opioid analgesics without the confounding CBT alterations.