NCT05935280

Mechanism of Human Cold Pain Perception - Involvement of TRPA1, TRPM8, Nav1.7 and Nav1.8

Human Cold Pain - a Single-group, Randomized, Placebo-controlled, Adaptive, Factorial Crossover Trial

• Status: Completed
• Phase: EARLY_Phase 1
• Study type: Interventional
• Enrollment: 36 (actual)
• Sponsor: Medical University of Vienna · Academic / Other
• Sex: All
• Age: 18 Years – 70 Years
• Healthy volunteers: Accepted

Summary

Animal studies suggest that the transient receptor potential ion channels TRPM8 and TRPA1 are cold sensors and that sodium channels Nav1.8 and Nav1.7 are essential for detecting pain induced by cold temperatures. This study aims to validate these findings in humans.

Detailed description

It is essential for human survival to be able to perceive potentially harmful cold. The perception of slight cooling in animals depends on the ion channel TRPM8, but this may represent a largely separate mechanism from painful cold. In mice, TRPM8 and TRPA1 appear to be involved, but also the sodium channels Nav1.7 and Nav1.8, through their temperature-dependent function. These receptors might be redundant, so that failure of individual receptors only leads to no or only a partial reduction in the detection of cold. Since results obtained in animals do not always translate to humans, the investigators want to clarify whether TRPM8, TRPA1, Nav1.7 and Nav1.8 are involved in the perception of cold pain in humans. In order to induce cold pain experimentally, an increasingly cooled solution (down to 3°C) is injected into the skin, and the inhibitors for the mentioned targets are added individually and in combination.

Conditions

• Pain

Interventions

Type	Name	Description
OTHER	Room temperature	Room temperature injection
OTHER	Cold temperature	Cold temperature injection
DRUG	Lidocain	Unspecific sodium channel blocker
DRUG	PF-05105679	Specific antagonist of the TRPM8 ion channel
DRUG	A967079	Specific antagonist of the TRPA1 ion channel
DRUG	PF-05089771	Specific antagonist of the Nav1.7 sodium channel
DRUG	PF-06305591	Specific antagonist of the Nav1.8 sodium channel

Timeline

• Start date: 2023-07-07
• Primary completion: 2023-09-01
• Completion: 2023-09-01
• First posted: 2023-07-07
• Last updated: 2024-03-15

Locations

1 site across 1 country: Austria