Effect of Anticipated Pain on Corticospinal Excitability

Overview

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.

Pain-related processes involve not only sensory inputs but also cognitive and emotional factors such as expectation, fear, and anticipation. Anticipating pain can influence motor behavior and emotional responses even in the absence of actual nociceptive stimulation. These anticipatory mechanisms are thought to contribute to maladaptive motor adaptations and may play a role in the development and maintenance of chronic pain conditions. However, the neurophysiological effects of pain anticipation, independently of real pain, remain insufficiently understood. The aim of this study is to examine the effect of pain anticipation on corticospinal excitability, a neurophysiological marker of motor cortex responsiveness and brain-to-muscle communication. Corticospinal excitability is assessed using transcranial magnetic stimulation (TMS) applied over the primary motor cortex. This non-invasive technique allows evaluation of motor pathway function through the elicitation of motor evoked potentials recorded from a target hand muscle. To specifically investigate anticipation-related effects, the study uses an experimental paradigm designed to manipulate pain expectancy without inducing actual pain. In addition to neurophysiological measures, psychological factors related to fear of movement and physiological markers of autonomic nervous system activity are considered, as they may influence the impact of pain anticipation on motor system function. Procedures : After providing informed consent, participants take part in a single experimental session conducted in a laboratory setting. The session begins with baseline assessments designed to characterize neurophysiological, psychological, and autonomic parameters prior to any experimental manipulation. Participants first complete self-report questionnaires assessing fear of movement, catastrophizing and pain-related avoidance beliefs (EKT-CF, PCS-CF and FACS-CF). Baseline measurements of corticospinal excitability are then obtained using transcranial magnetic stimulation (TMS) applied over the primary motor cortex. The TMS will be used to establish the input-output (I/O) curves. Stimuli of variable intensity between the threshold value (or MT for motor threshold) and the maximum will be delivered. In total, about ten stimulation intensities will be tested, and for each stimulation intensity, ten stimuli will be delivered, allowing then to calculate the average of the MEPs in order to draw the I/O curves of each participant. The resulting motor evoked potentials to characterize global corticospinal responsiveness. As recalled by national and international recommendations, TMS is a noninvasive and painless technique whose use in the scientific literature is extremely abundant. In parallel, baseline autonomic activity is recorded using heart rate variability measures. Following baseline assessments, participants are randomly assigned to either an experimental group or a control group. In both groups, an inert cream is applied to a predefined area of the forearm. The manipulation differs only in the information provided to participants. Those assigned to the experimental group are informed that the cream is expected to induce painful sensations (such as burning or tingling) after an approximate delay of ten minutes, with the pain progressively increasing in intensity over time, whereas participants in the control group are informed that the cream is inactive and will not produce any sensation. In reality, the same inert cream is used for all participants. This procedure is designed to induce anticipation of pain in the experimental group without exposing participants to actual nociceptive stimulation. Immediately after the application of the cream and the expectancy manipulation, corticospinal excitability is reassessed using the same TMS procedures as at baseline. Measurements are repeated to examine changes in motor system excitability associated with pain anticipation. Autonomic nervous system activity continues to be monitored throughout this phase. To reinforce the anticipatory context, additional TMS measurements, using the same procedures, are performed around the time when participants in the experimental group are led to expect the onset of pain (approximatively 10 minutes after cream application). This allows assessment of corticospinal excitability during heightened anticipation, independently of any real sensory input. At the end of the experimental session, participants are asked to report their perceived pain and level of apprehension during the study. A full debriefing is then conducted, during which the true purpose of the study and the use of expectancy manipulation are explained. Participants are given the opportunity to ask questions and withdraw their data if they wish. The duration of the experimental session is estimated at 1h30min, distributed as follows: Information, eligibility and consent collection, questionnaires completion : 20 minutes; preparation of the experiment (installation of the electrodes, setting of the devices: 10 minutes; recordings: 1 hour).