Pain
Conditions
Keywords
Psychophysics, Human physiology, Cold perception, Transient receptor potential ion channels, Voltage-gated sodium channels, Sensory neuron
Brief 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.
Interventions
OTHERRoom temperature
Room temperature injection
OTHERCold temperature
Cold temperature injection
DRUGLidocain
Unspecific sodium channel blocker
DRUGPF-05105679
Specific antagonist of the TRPM8 ion channel
DRUGA967079
Specific antagonist of the TRPA1 ion channel
DRUGPF-05089771
Specific antagonist of the Nav1.7 sodium channel
DRUGPF-06305591
Specific antagonist of the Nav1.8 sodium channel
Sponsors
Medical University of Vienna
Study design
Allocation
RANDOMIZED
Intervention model
SINGLE_GROUP
Primary purpose
BASIC_SCIENCE
Masking
QUADRUPLE (Subject, Caregiver, Investigator, Outcomes Assessor)
Intervention model description
This study is a randomized, placebo-controlled, crossover trial. The factors determining the conditions varied within individuals are 'TRPM8 inhibitor', 'TRPA1 inhibitor', 'Nav1.7 inhibitor', 'Nav1.8 inhibitor' each with the levels 'inhibitor' or 'control'. The design allows estimating the effect size caused by each factor alone, as well as the fractional inhibition achieved when all four channels are blocked. In a separate condition, the hypothesized action of lidocaine against nerve conduction, thus including cold-induced activity, is intended as positive control.
Eligibility
Sex/Gender
ALL
Age
18 Years to 70 Years
Healthy volunteers
Yes
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
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| AUC Pain3°C | Through study completion, on average 90 minutes. | 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). |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| AUC Pain | Through study completion, on average 90 minutes. | 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). |
Countries
Austria
Outcome results
None listed