NCT05275751

Mechanisms of Human Heat Perception - Involvement of TRPA1, TRPV1 and TRPM3

Human Heat Sensation - a Single-group, Randomized, Placebo-controlled, Adaptive, Full-factorial Crossover Trial

• Status: Completed
• Phase: EARLY_Phase 1
• Study type: Interventional
• Enrollment: 51 (actual)
• Sponsor: Medical University of Vienna · Academic / Other
• Sex: All
• Age: 18 Years – 70 Years
• Healthy volunteers: Accepted

Summary

Animal studies suggest that the ion channels TRPV1, TRPA1 and TRPM3 are the relevant heat sensors. This study aims to validate these findings in humans.

Detailed description

Surprisingly, it is still not fully understood how humans perceive heat pain. There are several heat-sensitive ion channels whose manipulation in animals resulted in a more or less pronounced phenotype. However, complete blockade of heat sensation in animals has only recently been achieved. In triple knockout mice lacking TRPA1, TRPV1 and TRPM3, it was recently shown that only in the absence of all three receptors heat perception is largely abolished. Although the authors were unable to elucidate the underlying mechanism of this redundancy, the redundancy appears to have evolutionary value for protection against burns. In addition, recent evidence suggests that TRPV1 plays a role as a first-line defense against heat injury, i.e., that it encodes noninjurious heat injury in humans. The goal of this study is to test whether the redundant functions of TRPV1, TRPA1 and TRPM3 observed in mice with respect to heat perception also apply to humans. More broadly, we want to understand which receptors enable humans to perceive heat pain. The study also aims to test if a chloride channel is involved in heat perception. Design: Cross-over study with a Williams design group, 16 treatments incl. a placebo control.

Conditions

• Pain

Interventions

Type	Name	Description
DRUG	TRPA1-inhibitor	Pharmacological inhibition of TRPA1 during intradermal injection of hot synthetic interstitial fluid
DRUG	TRPV1-inhibitor	Pharmacological inhibition of TRPV1 during intradermal injection of hot synthetic interstitial fluid
DRUG	TRPM3-inhibitor	Pharmacological inhibition of TRPM3 during intradermal injection of hot synthetic interstitial fluid
DRUG	Placebo	No pharmacological intervention
DRUG	Chloride-channel inhibitor	Pharmacological inhibition of a chloride channel during intradermal injection of hot synthetic interstitial fluid

Timeline

• Start date: 2022-06-13
• Primary completion: 2022-11-30
• Completion: 2022-11-30
• First posted: 2022-03-11
• Last updated: 2023-03-17

Locations

1 site across 1 country: Austria