Effect of Anticipated Pain on Corticospinal Excitability

NCT07407595 | Active Not Recruiting

• 1 other identifier: 2025-A00353-46
• Study Type: interventional
• Target: 44
• Locations: 1 country
• Sites: 1

Brief Summary

The purpose of this study is to investigate how the anticipation of pain, in the absence of real pain, affects the excitability of the corticospinal pathway. Corticospinal excitability reflects how responsive the motor areas of the brain are when sending signals to muscles. In this study, healthy adult participants will be randomly assigned to one of two groups. Both groups will receive the application of an inert cream on the forearm. Participants in the experimental group will be told that the cream may cause pain, while participants in the control group will be informed that the cream is completely inactive. In reality, the cream has no physical effect in either group. This design allows the researchers to isolate the effect of pain anticipation (a nocebo effect) without exposing participants to actual pain. Corticospinal excitability will be measured using transcranial magnetic stimulation (TMS), a non-invasive technique that stimulates the motor cortex to assess brain-to-muscle communication. Measurements will be taken before and after the application of the cream. In addition, psychological factors related to catastrophizing and fear of movement will be assessed using validated questionnaires, and physiological responses associated with stress will be measured through heart rate variability. The main question this study aims to answer is whether anticipating pain, even without experiencing real pain, alters corticospinal excitability, and whether this effect is influenced by fear of movement and catastrophizing. By improving our understanding of how pain-related expectations affect brain function, this research may contribute to better strategies for preventing maladaptive motor changes associated with chronic pain.

Conditions

Nocebo Effect; Kinesiophobia

Keywords

Pain anticipation; Nocebo effect; Kinesiophobia; Corticospinal excitability; Transcranial magnetic stimulation

Outcome Measures

Primary Outcomes (1)

• Change from baseline in corticospinal excitability

  Corticospinal excitability will be assessed using transcranial magnetic stimulation (TMS) applied over the primary motor cortex. Single magnetic pulses of increasing intensity will be delivered to construct input-output (I/O) recruitment curves for each participant at baseline, immediately after cream application, and 10 minutes after cream application. Stimulation intensity will be increased in 3-5% steps, and 10 stimuli will be delivered at each intensity level. Motor evoked potentials elicited by TMS will be recorded using surface electromyography from the first dorsal interosseous muscle of the hand. I/O curves will be modeled using a Boltzmann sigmoidal function, and the slope, plateau, and S50 parameters will be extracted. Changes in corticospinal excitability will be compared between groups across these time points.

  During single session: baseline (pre-cream application), immediately post-cream application, and 10 minutes post-cream application

Secondary Outcomes (5)

• Fear-avoidance beliefs related to pain

  Baseline

• Kinesiophobia

  Baseline

• Change in heart rate variability from Baseline

  During the single study session, from the baseline resting period through completion of the TMS procedure (up to 60 minutes)

• Pain catastrophizing related to pain

  Baseline

• Change from baseline in intracortical inhibition and facilitation (SICI and SICF)

  During single session: baseline (pre-cream application), immediately post-cream application, and 10 minutes post-cream application

Other Outcomes (3)

• Brief Pain Inventory

  Baseline

• Change from baseline in perceived apprehension

  During the single study session: baseline (pre-cream application), immediately post-cream application, and 10 minutes post-cream application

• Change from baseline in perceived pain intensity

  During the single study session: baseline (pre-cream application), immediately post-cream application, and 10 minutes post-cream application

Study Arms (2)

Control Group - Inert Cream (Neutral Information)

OTHER

Participants in this control arm receive the application of an inert cream on the forearm. They are informed that the cream is inactive and will not produce any sensation or effect. This arm serves as a control condition for the manipulation of pain anticipation, with identical procedures and measurements as the experimental arm, except for the information provided about the expected effects of the cream.

Other: Pain Expectation Manipulation

Experimental Group - Inert Cream (Pain Expectation Information)

EXPERIMENTAL

Participants in this experimental arm receive the application of an inert cream on the forearm. They are informed that the cream is expected to induce painful sensations after a delay, with pain gradually increasing in intensity over time. This information is used to induce anticipation of pain without actual nociceptive stimulation. All procedures and measurements are identical to those of the control arm, except for the information provided about the expected effects of the cream.

Other: Pain Expectation Manipulation

Interventions

Pain Expectation Manipulation OTHER

The intervention consists of an information-based manipulation designed to induce (or not induce) anticipation of pain. Participants receive the application of an inert cream on the forearm. Depending on group assignment, participants are informed either that the cream is inactive and will not produce any sensation, or that it is expected to produce painful sensations such as burning, stinging, or tingling, with onset approximately 10 minutes after application and a gradual increase in intensity over time, reaching a moderate to strong level of perceived pain. The cream itself has no active or sensory effects in any group. This intervention allows manipulation of pain expectation without inducing actual nociceptive stimulation.

Control Group - Inert Cream (Neutral Information); Experimental Group - Inert Cream (Pain Expectation Information)

Eligibility Criteria

• Age: 18 Years - 65 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Adults aged 18 to 65 years.
• Ability to understand spoken and written French sufficient to follow study procedures.
• Written informed consent obtained prior to participation.
• Subjects affiliated with or receiving social security benefits

You may not qualify if:

• 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 history of skin reaction to any component of the inert cream used in the study (Medicafarm® Neutre Premium Longue Glisse).

Sponsors & Collaborators

• Universite du Littoral Cote d'Opale: lead

Study Sites (1)

Eurasport

Loos, Nord, 59120, France

Location

MeSH Terms

Conditions

Kinesiophobia

Condition Hierarchy (Ancestors)

Phobic Disorders; Anxiety Disorders; Mental Disorders

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: RANDOMIZED
• Masking: NONE
• Masking Details: A randomized number is allocated for all participants.
• Purpose: BASIC SCIENCE
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Model Details: Participants are randomly assigned to one of two parallel groups. Both groups receive the application of the same inert cream. The experimental group is informed that the cream is expected to induce pain, whereas the control group is informed that the cream is inactive.

Study Record Dates

• First Submitted: December 17, 2025
• First Posted: February 12, 2026
• Study Start: February 12, 2026
• Primary Completion: July 1, 2026
• Study Completion: July 1, 2026
• Last Updated: February 13, 2026

Record last verified: 2026-02

Data Sharing

• IPD Sharing: Will not share

Locations

FR (1)