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

Early Phase 1CompletedNCT05935280

Medical University of Vienna36 enrolled

Overview

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.

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.

Study Type

INTERVENTIONAL

Allocation

RANDOMIZED

Purpose

BASIC_SCIENCE

Masking

QUADRUPLE

Enrollment

Conditions

Pain

Interventions

Room temperatureOTHER

Room temperature injection

Cold temperatureOTHER

Cold temperature injection

LidocainDRUG

Unspecific sodium channel blocker

PF-05105679

Eligibility

Sex: ALLMin age: 18 YearsMax age: 70 YearsHealthy volunteers:

Medical Language ↔ Plain English

Inclusion Criteria: * Age between 18 and 70 years * Full legal capacity To ensure an equal number of each sex in the study population, only volunteers of one sex will be included as soon as the number of subjects with the other sex has reached half of the calculated sample size. Exclusion Criteria: * Participant of another study, ongoing or within the last 4 weeks * Medication intake (except contraception) or drug abuse * Female subjects: Positive pregnancy test or breastfeeding * Body temperature above 38°C, diagnostically verified * Known allergic diseases, in particular asthmatic disorders and skin diseases * Sensory deficit, skin disease or hematoma of unknown origin in physical examination of the test site

Locations (1)

Medical University of Vienna

Vienna, Austria

Outcomes

Primary Outcomes

AUC Pain3°C

The primary outcome variable is the area under the curve (AUC) of pain ratings over a limited duration of the infusion period, i.e. from 120-150 seconds (last 30 seconds of the cold stimulus).

Time frame: Through study completion, on average 90 minutes.

Secondary Outcomes

AUC Pain

The secondary outcome variable is the area under the curve (AUC) of pain ratings over the full duration of the infusion period (full 150 seconds of the cold stimulus).

Time frame: Through study completion, on average 90 minutes.

Data from ClinicalTrials.gov

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