Background and aims: Experimental prolonged pain models can shed more light on the cortical mechanisms involved in the transition from acute to chronic pain including changes in resting state functional connectivity (rsFC). This experiment aimed at examining the effect of 24-hour-capsaicin application on the rsFC of the default mode network (DMN), a prominent network in the dynamic pain connectome. Methods: Electroencephalographic (EEG) rsFC measured by Granger causality was acquired at baseline, 1-hour, and 24-hour following the initial patch application (placebo or capsaicin). After 24 hours, the patch was cooled down then heated up to assess rsFC changes in response to pain relief and facilitation. Pain was induced using a topical capsaicin patch (or placebo as control) on the right forearm and assessed on a 0-10 numerical rating scale (NRS).
Study Type
INTERVENTIONAL
Allocation
NON_RANDOMIZED
Purpose
BASIC_SCIENCE
Masking
SINGLE
Enrollment
24
Cutaneous pain was induced using a (5x10 cm) 8% topical capsaicin patch (transdermal patch, 'Qutenza', Astellas) on the volar part of the dominant right forearm (5 cm from the wrist) of each participant.
A transparent patch with no formulation or effect but the same size of the capsaicin patch was applied to the same location.
Aalborg University, Department of Health Sciences and technology
Aalborg, Denmark
Change in resting state functional connectivity
resting state functional connectivity is assessed using Granger causality. It can take on any value starting with "0" representing no connectivity. Higher granger causality scores indicate higher connectivity.
Time frame: Granger causality is assessed at 5 time points for each condition (capsaicin or placebo): baseline, 1 hour, 24 hours, 24 hours, cooling at 24hours, and heating at 24 hours.
Change in Subjective pain intensity
Intensity rated by the participants on a numerical rating scale anchoring from 0 "no pain" to 10 "the worst imaginable pain" . Higher numerical rating scores indicate higher pain intensity.
Time frame: Intensity is assessed at 5 time points for each condition (capsaicin or placebo): baseline, 1 hour, 24 hours, cooling at 24hours, and heating at 24 hours.
Change in Pain sensitivity (Warmth detection threshold)
Warmth detection threshold is assessed using a thermal stimulator probe (3 × 3 cm, Pathway Medoc Ltd, Israel). Higher threshold scores indicate less sensitivity. .
Time frame: Warmth detection threshold is assessed at 3 time points for each condition (capsaicin or placebo): baseline, 1 hour, and 24 hours.
Change in Pain sensitivity ( Cold detection threshold).
Cold detection threshold is assessed using a thermal stimulator probe (3 × 3 cm, Pathway Medoc Ltd, Israel). Higher threshold scores indicate less sensitivity.
Time frame: Warmth detection threshold is assessed at 3 time points for each condition (capsaicin or placebo): baseline, 1 hour, and 24 hours.
Change in Pain sensitivity ( Heat pain threshold).
Heat detection threshold is assessed using a thermal stimulator probe (3 × 3 cm, Pathway Medoc Ltd, Israel). Higher threshold scores indicate less sensitivity.
Time frame: Heat pain threshold is assessed at 3 time points for each condition (capsaicin or placebo): baseline, 1 hour, and 24 hours.
Change in Pain sensitivity ( Cold pain thresholds).
Cold pain threshold is assessed using a thermal stimulator probe (3 × 3 cm, Pathway Medoc Ltd, Israel). Higher threshold scores indicate less sensitivity.
Time frame: Cold pain threshold is assessed at 3 time points for each condition (capsaicin or placebo): baseline, 1 hour, and 24 hours.
Change in Pain sensitivity ( Mechanical pain thresholds).
Mechanical pain thresholds was assessed using a set of seven weighted pinprick stimulators consisting of steel tubes ending with a tip contact area of 0.25 mm diameter and excreting forces of 0.8, 1.6, 3.2, 6.4, 12.8, 25.6, and 51.2 g. Higher threshold scores indicate less sensitivity.
Time frame: Mechanical pain threshold is assessed at 3 time points for each condition (capsaicin or placebo): baseline, 1 hour, and 24 hours.
Pain vigilance
Pain Vigilance and Awareness Questionnaire (PVAQ). This questionnaire consists of 16 items evaluating preoccupation and attention to one's pain over the past two weeks, rated between 0 = "never" and 5 = "always", with a maximum score of 80. The higher the scores, the higher the preoccupation with pain.
Time frame: It is assessed at baseline and after 24 hours for each condition (capsaicin or placebo).
Pain Catastrophizing
Scale (PCS). This questionnaire comprises 13 items assessed on a 5-point scale ranging from 0 = "not at all" to 4 = "all the time", with a maximum score of 52. It evaluates three scales of catastrophizing: rumination, magnification, and helplessness. Ratings reflect the degree to which specific thoughts and feelings are present when experiencing pain over the last three months. Higher scores indicate a higher degree of pain catastrophizing.
Time frame: It is assessed at baseline and after 24 hours for each condition (capsaicin or placebo).
Sleep quality assessment
Pittsburgh Sleep Quality Index (PSQI). This questionnaire determines sleep quality and sleep patterns across seven areas: subjective sleep quality, sleep latency, sleep duration, habitual sleep efficiency, sleep disturbances, use of sleeping medication, and daytime dysfunction over the last month. These areas are evaluated on a scale ranging from 0 = "no difficulty" to 3 = "severe difficulty," with a maximum score of 21. Higher scores reflect poor sleep quality.
Time frame: It is assessed at baseline and after 24 hours for each condition (capsaicin or placebo).
Fatigue assessment
Modified Fatigue Impact Scale (MFIS). The MFIS evaluates the degree to which fatigue influences overall perceived function over the last 4 weeks. It assesses three subscales: cognitive (9 items), physical (10 items), and psychosocial (2 items) functioning. Items are measured on a scale from 0 = "no problem" to 4 = "extreme problem", with a maximum score of 120. Higher scores indicate higher levels of fatigue.
Time frame: It is assessed at baseline and after 24 hours for each condition (capsaicin or placebo).
Positive and negative affect
Positive and Negative Affect Scale (PANAS). This scale consists of 20 items assessing two groups of emotions: negative and positive (10 items each). Subjects rate the intensity of a specific emotion they are experiencing at the moment on a scale (1 = "very slightly or not at all" to 5 = "Extremely"). for each emotion group with a maximum of 50. Higher scores indicate more intense emotions. The positive affect items were "interested," "excited," "strong," "enthusiastic," "proud," "alert," "inspired," "determined," "attentive," and "active." The negative affect items were "distressed," "upset," "guilty," "scared," "hostile," "irritable," "ashamed," "nervous," "jittery," and "afraid."
Time frame: They are assessed at baseline and after 24 hours for each condition (capsaicin or placebo).
Depression scores
Beck Depression Inventory (BDI-II). The BDI determines the severity of depressive mood states and consists of 21 questions assessing hopelessness, guilt, fatigue, and other physical symptoms, rated between 0 = "no symptom impact" and 3 = "maximum symptom impact" with a maximum score of 63. Higher scores indicate severe depressive symptoms. To obtain measures of trait depression, subjects in this study are instructed to rate the items in relation to how they generally feel.
Time frame: They are assessed at baseline and after 24 hours for each condition (capsaicin or placebo).
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