Pain Beliefs and Intracortical Excitability During Experimental Pain

Influence Of Pain-Related Beliefs On The Modulation Of Intracortical Circuits During Experimental Pain Induced By Topical Capsaicin

Pain can influence the way the motor system functions. However, responses to pain vary widely between individuals, and this variability may be partly related to pain-related beliefs such as kinesiophobia.

This study examines whether temporary experimental pain changes intracortical excitability in the motor cortex, and whether this response differs according to baseline kinesiophobia. Healthy adults will complete one experimental session. Motor cortex excitability will first be assessed at baseline using transcranial magnetic stimulation, a non-invasive brain stimulation technique. A topical capsaicin cream will then be applied to the forearm to induce temporary, moderate experimental pain. Once pain is established, the same neurophysiological assessments will be repeated.

The main objective is to measure changes in short-interval intracortical inhibition before and during capsaicin-induced pain, with particular attention to whether these changes are associated with baseline kinesiophobia.

Secondary objectives are to characterize other markers of motor cortex excitability, including long-interval intracortical inhibition, short-interval intracortical facilitation, intracortical facilitation, and corticospinal excitability assessed using input-output recruitment curves. Pain intensity will be monitored using a visual analog scale to characterize the experimental pain response. Baseline kinesiophobia will be assessed using the Tampa Scale of Kinesiophobia and examined as a factor associated with interindividual variability in neurophysiological responses to experimental pain.

The researchers expect that changes in motor cortex excitability during experimental pain will vary between individuals, and that individuals with higher kinesiophobia may show smaller changes in motor cortex excitability during capsaicin-induced pain.

Study Overview

• Status: Not yet recruiting
• Conditions: Experimental Pain; Kinesiophobia (Fear of Movement)
• Intervention / Treatment: Drug: Topical Capsaicin Cream (1%)

Detailed Description

Pain is not only a sensory experience. It is also influenced by psychological, emotional, and contextual factors, including how people interpret pain and the threat they associate with movement. In the presence of pain, individuals often modify the way they move. These adaptations may be protective in the short term, but when maintained over time, they may contribute to persistent movement avoidance and disability.

Within the fear-avoidance framework, kinesiophobia, or fear of movement, is considered an important factor in the relationship between pain, movement, and disability. Individuals with higher kinesiophobia may perceive movement as threatening or potentially harmful. This may influence not only motor behavior, but also the way the nervous system prepares and controls movement. However, the neurophysiological mechanisms linking pain-related beliefs, experimental pain, and motor control remain incompletely understood.

The primary motor cortex is a key brain region involved in voluntary movement. Its excitability can be assessed using transcranial magnetic stimulation, a non-invasive brain stimulation technique. When applied over the primary motor cortex, transcranial magnetic stimulation can evoke motor responses that are recorded from a target muscle using surface electromyography. These responses provide information about corticospinal excitability and about intracortical inhibitory and facilitatory mechanisms.

Previous studies suggest that experimental pain can modify motor cortex excitability, but the direction and magnitude of these changes vary considerably between individuals. Pain-related beliefs, especially kinesiophobia, may partly explain this variability. This study therefore focuses on whether experimental pain changes intracortical excitability in the motor cortex and whether this response differs according to baseline kinesiophobia.

The main objective is to quantify changes in short-interval intracortical inhibition before and during experimental pain induced by topical capsaicin, with particular attention to whether these changes vary according to the participant's baseline level of kinesiophobia. Short-interval intracortical inhibition is used as the primary neurophysiological measure because it reflects inhibitory activity within the motor cortex.

Secondary objectives are to characterize other markers of motor cortex excitability during experimental pain. These include long-interval intracortical inhibition, intracortical facilitation, and corticospinal excitability assessed using input-output recruitment curves. These complementary measures are included to provide a broader characterization of inhibitory, facilitatory, and corticospinal responses to experimental pain.

Healthy adults will complete one experimental session. At the beginning of the session, participants will complete questionnaires assessing pain-related beliefs, including kinesiophobia. Baseline neurophysiological assessments will then be performed using transcranial magnetic stimulation applied over the primary motor cortex, with electromyographic recordings from the first dorsal interosseous muscle of the hand.

After baseline measurements, topical capsaicin cream will be applied to the forearm to induce temporary, moderate experimental pain. Pain intensity will be monitored using a visual analog scale. Once experimental pain is established, the same transcranial magnetic stimulation assessments will be repeated.

Each participant serves as their own control, with neurophysiological measures compared between the baseline condition and the experimental pain condition. The investigators hypothesize that changes in motor cortex excitability during experimental pain will vary between individuals. This variability is expected to be partly related to kinesiophobia, with individuals reporting higher kinesiophobia showing smaller changes in motor cortex excitability during capsaicin-induced pain.

• Study Type: Interventional
• Enrollment (Estimated): 30
• Phase: Not Applicable

Contacts and Locations

• Study Contact: Name: Guillaume Léonard, Ph.D.; Phone Number: 819-821-8000; Email: guillaume.leonard2@usherbrooke.ca
• Study Contact Backup: Name: Adrien Nourry; Phone Number: +33611074458; Email: adrien.nourry@usherbrooke.ca

Study Locations

• Canada
  • Quebec
    • Sherbrooke, Quebec, Canada, J1H 5H3
      • Université de Sherbrooke - Campus de la santé
      • Contact: Guillaume Léonard, Ph.D.; Phone Number: 819-821-8000; Email: guillaume.leonard2@usherbrooke.ca
      • Contact: Adrien Nourry; Phone Number: +33611074458; Email: adrien.nourry@usherbrooke.ca
      • Principal Investigator: Guillaume Léonard, Ph.D.

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult
• Accepts Healthy Volunteers: Yes

Description

Inclusion Criteria:

• Aged 18 to 35 years, inclusive
• Healthy
• Able to understand the study information and experimental procedures
• Able to provide informed consent

Exclusion Criteria:

• History of psychiatric disorders (including intellectual disability or severe cognitive, behavioral, or affective impairment) that could interfere with understanding the study or providing informed consent.
• History of neurological disorders, including epilepsy, stroke, brain or spinal cord surgery, or any neurological disease affecting motor or sensory function.

Inability to provide informed consent (e.g., dementia, significant hearing impairment, insufficient language proficiency).

• Any pain condition within the past 3 months, regardless of origin.
• Recent musculoskeletal injury or surgery within the past 3 months.
• Contraindications to transcranial magnetic stimulation (TMS), including a history of epilepsy or the presence of intracranial metallic objects, cochlear implants, or other non-removable metallic implants in or near the head.
• Use of analgesic or psychotropic medications.
• Individuals under legal guardianship or curatorship.
• Pregnant or breastfeeding women.
• Presence of a cardiac pacemaker or other implanted electronic medical device.
• Known allergy or previous skin reaction to capsaicin

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Basic Science
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm

Intervention / Treatment

Experimental: Experimental pain; Participants complete one experimental session. Motor cortex excitability is first assessed at baseline using transcranial magnetic stimulation with electromyographic recordings from the first dorsal interosseous muscle. Topical capsaicin cream is then applied to the forearm to induce temporary, moderate experimental pain. Once pain is established, the same neurophysiological assessments are repeated during the pain condition.

Drug: Topical Capsaicin Cream (1%); Topical capsaicin cream (1%) is applied to the forearm to induce temporary, moderate experimental pain. Motor cortex excitability is assessed before and during capsaicin-induced pain using transcranial magnetic stimulation.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change in Short-Interval Intracortical Inhibition	Short-interval intracortical inhibition will be assessed using paired-pulse transcranial magnetic stimulation over the primary motor cortex, with electromyographic recordings from the first dorsal interosseous muscle. A subthreshold conditioning stimulus set at 80% of resting motor threshold will be followed by a suprathreshold test stimulus set at 120% of resting motor threshold, with an interstimulus interval of 3 ms. Fifteen conditioned trials will be recorded for this measure. The outcome will be expressed as the change in conditioned motor evoked potential amplitude relative to the unconditioned test response from pre- to post-application of topical capsaicin cream.	At baseline (before capsaicin cream application); at pain stabilization (after capsaicin cream application)

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change in Short-Interval Intracortical Facilitation	Short-interval intracortical facilitation will be assessed using paired-pulse transcranial magnetic stimulation over the primary motor cortex, with electromyographic recordings from the first dorsal interosseous muscle. A suprathreshold conditioning stimulus set at 120% of resting motor threshold will be followed by a subthreshold test stimulus set at 80% of resting motor threshold, with an interstimulus interval of 2 ms. Fifteen conditioned trials will be recorded for this measure. The outcome will be expressed as the change in conditioned motor evoked potential amplitude relative to the unconditioned test response from pre- to post-application of topical capsaicin cream.	At baseline (before capsaicin cream application); at pain stabilization (after capsaicin cream application)
Change in Pain Intensity	Pain intensity will be assessed using a visual analog scale ranging from 0 to 10, where 0 indicates no pain and 10 indicates the worst imaginable pain. The outcome will be expressed as the change in pain intensity from pre- to post-application of topical capsaicin cream.	From baseline through completion of the experimental session, an average of 2 hours
Change in Intracortical Facilitation	Intracortical facilitation will be assessed using paired-pulse transcranial magnetic stimulation over the primary motor cortex, with electromyographic recordings from the first dorsal interosseous muscle. A subthreshold conditioning stimulus set at 80% of resting motor threshold will be followed by a suprathreshold test stimulus set at 120% of resting motor threshold, with an interstimulus interval of 15 ms. Fifteen conditioned trials will be recorded for this measure. The outcome will be expressed as the change in conditioned motor evoked potential amplitude relative to the unconditioned test response from pre- to post-application of topical capsaicin cream.	At baseline (before capsaicin cream application); at pain stabilization (after capsaicin cream application)
Change in Long-Interval Intracortical Inhibition	Long-interval intracortical inhibition will be assessed using paired-pulse transcranial magnetic stimulation over the primary motor cortex, with electromyographic recordings from the first dorsal interosseous muscle. A suprathreshold conditioning stimulus set at 120% of resting motor threshold will be followed by a suprathreshold test stimulus set at 120% of resting motor threshold, with an interstimulus interval of 100 ms. Fifteen conditioned trials will be recorded for this measure. The outcome will be expressed as the change in conditioned motor evoked potential amplitude relative to the unconditioned test response from pre- to post-application of topical capsaicin cream.	At baseline (before capsaicin cream application); at pain stabilization (after capsaicin cream application)
Change from baseline in corticospinal excitability	Corticospinal excitability will be assessed using single-pulse transcranial magnetic stimulation applied over the primary motor cortex, with electromyographic recordings from the first dorsal interosseous muscle. Single magnetic pulses of increasing intensity will be delivered to construct input-output recruitment curves for each participant. Stimulation intensity will be increased in 5% steps, and 10 stimuli will be delivered at each intensity level. Motor evoked potentials will be recorded using surface electromyography. Input-output curves will be modeled using a Boltzmann sigmoidal function, and the slope, plateau, and S50 parameters will be extracted. The outcome will be expressed as the change in these input-output curve parameters from pre- to post-application of topical capsaicin cream.	At baseline (before capsaicin cream application); at pain stabilization (after capsaicin cream application)

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
Pain catastrophizing related to pain	Pain catastrophizing will be assessed using the French-Canadian version of the Pain Catastrophizing Scale (PCS-CF), a self-report questionnaire designed to measure catastrophic thoughts related to pain. The PCS-CF includes 13 items rated on a Likert scale from 0 ("not at all") to 4 ("all the time"), covering three dimensions: rumination, magnification, and helplessness. Item scores are summed to yield a total score ranging from 0 to 52, with higher scores indicating greater pain catastrophizing. A total score ≥30 has been proposed to identify clinically relevant levels of pain catastrophizing.	Baseline
Kinesiophobia	Kinesiophobia will be assessed using the French-Canadian version of the Tampa Kinesiophobia Questionnaire (EKT-CF). It takes the form of a self-reported questionnaire of 17 items using a Likert scale ranging from 1 (strongly disagree) to 4 (strongly agree), with an acceptable degree of internal consistency (Cronbach's alpha = 0.71), satisfactory construct validity, and high sensitivity to change (intra-class correlation coefficient > 0.7). The total score is obtained by adding the value of the responses and is between 17 and 68. The value of 37/68 is considered as the threshold value at which kinesiophobia becomes significant.	Baseline

Collaborators and Investigators

• Sponsor: Université de Sherbrooke
• Investigators: Principal Investigator: Guillaume Léonard, Ph.D., Université de Sherbrooke

Study record dates

Study Major Dates

• Study Start (Estimated): August 1, 2026
• Primary Completion (Estimated): November 30, 2026
• Study Completion (Estimated): December 31, 2026

Study Registration Dates

• First Submitted: June 25, 2026
• First Submitted That Met QC Criteria: July 2, 2026
• First Posted (Actual): July 7, 2026

Study Record Updates

• Last Update Posted (Actual): July 7, 2026
• Last Update Submitted That Met QC Criteria: July 2, 2026
• Last Verified: July 1, 2026

More Information

Terms related to this study

• Keywords: Transcranial magnetic stimulation; Kinesiophobia; Experimental pain; Corticospinal excitability; Fear of movement; Topical capsaicin; Motor cortex excitability; Intracortical excitability
• Additional Relevant MeSH Terms: Mental Disorders; Phobic Disorders; Anxiety Disorders; Kinesiophobia
• Other Study ID Numbers: 2027-6267

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No