Pain, Sleep and Gut Microbiota

NCT ID: NCT05494983

Last Updated: 2024-01-30

Study Results

Results pending

The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.

Basic Information

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Recruitment Status

RECRUITING

Clinical Phase

NA

Total Enrollment

140 participants

Study Classification

INTERVENTIONAL

Study Start Date

2022-07-04

Study Completion Date

2026-01-04

Brief Summary

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The objective of this study in healthy volunteers is to evaluate whether the composition of the gut microbiota and sleep quality influence the susceptibility to develop peripheral and central sensitization of pain pathways.

In two different experimental sessions, the following factors will be tested: the influence of the composition of the gut microbiota on the susceptibility to develop peripheral sensitization of nociceptors, and the susceptibility to develop central sensitization of pain pathways. To assess susceptibility to peripheral sensitization, a solution of capsaicin (the active component of chili pepper) will be applied to the skin to induce neurogenic inflammation produced by the release of substances from nociceptors at the peripheral level. This neurogenic inflammation is characterized by a transient redness of the skin that will be measured with an infrared camera. To evaluate the susceptibility to sensitization at the central level, a high frequency electrical stimulation will be applied to the skin. This stimulation induces an increase in sensitivity to mechanical stimulation secondary to central sensitization. The intensity, extent and duration of this mechanical hyperalgesia will therefore be used as a measure of susceptibility to central sensitization.

A stool sample and a blood sample will be taken. These samples will be used to characterize the composition of the intestinal microbiota, as well as the metabolites produced by this microbiota. These analyses will allow a comparison of the composition of the microbiota and the metabolites in subjects with a tendency to develop low vs. high sensitization at the peripheral and central levels.

Similarly, sleep quality and average sleep duration will be assessed using questionnaires and a measurement of the participant's activity using a wrist movement sensitive bracelet. This information will be used to assess whether some of the interindividual variability in developing peripheral or central sensitization might be related to differences in sleep quality.

Finally, systemic inflammation could be a factor modulated by sleep and gut microbiota, influencing pain perception and susceptibility to sensitization. For this reason, systemic pro- and anti-inflammatory cytokines will be measured in the blood sample.

Detailed Description

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Conditions

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Sensitization, Central Peripheral Sensitization Gut Microbiota Sleep Quality

Study Design

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Allocation Method

RANDOMIZED

Intervention Model

CROSSOVER

Primary Study Purpose

OTHER

Blinding Strategy

SINGLE

Participants

Study Groups

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Session 1 : Peripheral Session (left) - session 2 Central Session (right)

The susceptibility to develop peripheral sensitization will be assessed at the first experimental session, the stimulation will occur at the left forearm.

The susceptibility to develop central sensitization will be assessed at the second experimental session, the stimulation will occur at the right forearm.

In both experimental sessions, participants will have to fill questionnaires about the use of medications, the Stanford Sleepiness Scale, the Leeds Sleep Evaluation Questionnaire, and the first part of the State and Trait Anxiety Questionnaire. During sensory stimulation, an infrared camera will be used to measure pupil diameter which constitute an indirect correlate of stimulus-evoked phasic variations in activity of the locus coeruleus. In order to measure autonomic reactivity to pain stimuli, the heart rate variability will be measured by recording electrocardiography.

Group Type OTHER

Screening visit

Intervention Type OTHER

The participants will be screened for inclusion and exclusion criteria and will be asked to fill the following questionnaires : Pittsburgh Sleep Quality Index, State and Trait Anxiety Questionnaire, Pain Catastrophizing Scale Fear of Pain Questionnaire, Perceived Stress Scale, Beck Depression Inventory, and questionnaires to assess their health status and the use of medications. A blood sample (to measure pro- and anti-inflammatory cytokines and perform metabolomic analyses) will be obtained. Enrolled participants will be given a wearable actimeter to assess daily total sleep duration during one week before the first experimental session. They will also be requested to complete daily a sleep diary during one week before each experimental session, and a food diary before the first experimental session. A fecal sample (to assess gut microbiota composition and perform metabolomic analyses) will be collected between the screening visit and the first experimental session.

Peripheral sensitization session

Intervention Type OTHER

The extent of neurogenic inflammation induced by topical capsaicin will be used as a measure of the susceptibility to sensitize at peripheral level. A solution of capsaicin will be applied to the skin of the left or right volar forearm for 30 minutes. The capsaicin-induced neurogenic inflammation can be quantified by assessing the intensity, extent and duration of the capsaicin-induced cutaneous flare response using thermal infrared imaging. Using heat stimuli delivered to the treated skin and surrounding skin, the intensity and duration of the capsaicin-induced hyperalgesia will also be assessed. The experimental session will last approximately two hours.

Central sensitization session

Intervention Type OTHER

The extent of secondary mechanical hyperalgesia induced by high-frequency electrical stimulation (HFS) of the skin of the left or right volar forearm will be used as a measure of the susceptibility to develop central sensitization. The stimulation will be delivered using a multi-pin electrode designed to preferentially activate epidermal free nerve endings. The strength, spatial extent and duration of the HFS-induced changes in pinprick sensitivity will be characterized by using calibrated mechanical pinprick stimuli. The experimental session will last approximately one hour.

Session 1 : Peripheral Session (right) - session 2 Central Session (left)

The susceptibility to develop peripheral sensitization will be assessed at the first experimental session, the stimulation will occur at the right forearm.

The susceptibility to develop central sensitization will be assessed at the second experimental session, the stimulation will occur at the left forearm.

In both experimental sessions, participants will have to fill questionnaires about the use of medications, the Stanford Sleepiness Scale, the Leeds Sleep Evaluation Questionnaire, and the first part of the State and Trait Anxiety Questionnaire. During sensory stimulation, an infrared camera will be used to measure pupil diameter which constitute an indirect correlate of stimulus-evoked phasic variations in activity of the locus coeruleus. In order to measure autonomic reactivity to pain stimuli, the heart rate variability will be measured by recording electrocardiography.

Group Type OTHER

Screening visit

Intervention Type OTHER

The participants will be screened for inclusion and exclusion criteria and will be asked to fill the following questionnaires : Pittsburgh Sleep Quality Index, State and Trait Anxiety Questionnaire, Pain Catastrophizing Scale Fear of Pain Questionnaire, Perceived Stress Scale, Beck Depression Inventory, and questionnaires to assess their health status and the use of medications. A blood sample (to measure pro- and anti-inflammatory cytokines and perform metabolomic analyses) will be obtained. Enrolled participants will be given a wearable actimeter to assess daily total sleep duration during one week before the first experimental session. They will also be requested to complete daily a sleep diary during one week before each experimental session, and a food diary before the first experimental session. A fecal sample (to assess gut microbiota composition and perform metabolomic analyses) will be collected between the screening visit and the first experimental session.

Peripheral sensitization session

Intervention Type OTHER

The extent of neurogenic inflammation induced by topical capsaicin will be used as a measure of the susceptibility to sensitize at peripheral level. A solution of capsaicin will be applied to the skin of the left or right volar forearm for 30 minutes. The capsaicin-induced neurogenic inflammation can be quantified by assessing the intensity, extent and duration of the capsaicin-induced cutaneous flare response using thermal infrared imaging. Using heat stimuli delivered to the treated skin and surrounding skin, the intensity and duration of the capsaicin-induced hyperalgesia will also be assessed. The experimental session will last approximately two hours.

Central sensitization session

Intervention Type OTHER

The extent of secondary mechanical hyperalgesia induced by high-frequency electrical stimulation (HFS) of the skin of the left or right volar forearm will be used as a measure of the susceptibility to develop central sensitization. The stimulation will be delivered using a multi-pin electrode designed to preferentially activate epidermal free nerve endings. The strength, spatial extent and duration of the HFS-induced changes in pinprick sensitivity will be characterized by using calibrated mechanical pinprick stimuli. The experimental session will last approximately one hour.

Session 1 : Central Session (left) - session 2 Peripheral Session (right)

The susceptibility to develop central sensitization will be assessed at the first experimental session, the stimulation will occur at the left forearm.

The susceptibility to develop peripheral sensitization will be assessed at the second experimental session, the stimulation will occur at the right forearm.

In both experimental sessions, participants will have to fill questionnaires about the use of medications, the Stanford Sleepiness Scale, the Leeds Sleep Evaluation Questionnaire, and the first part of the State and Trait Anxiety Questionnaire. During sensory stimulation, an infrared camera will be used to measure pupil diameter which constitute an indirect correlate of stimulus-evoked phasic variations in activity of the locus coeruleus. In order to measure autonomic reactivity to pain stimuli, the heart rate variability will be measured by recording electrocardiography.

Group Type OTHER

Screening visit

Intervention Type OTHER

The participants will be screened for inclusion and exclusion criteria and will be asked to fill the following questionnaires : Pittsburgh Sleep Quality Index, State and Trait Anxiety Questionnaire, Pain Catastrophizing Scale Fear of Pain Questionnaire, Perceived Stress Scale, Beck Depression Inventory, and questionnaires to assess their health status and the use of medications. A blood sample (to measure pro- and anti-inflammatory cytokines and perform metabolomic analyses) will be obtained. Enrolled participants will be given a wearable actimeter to assess daily total sleep duration during one week before the first experimental session. They will also be requested to complete daily a sleep diary during one week before each experimental session, and a food diary before the first experimental session. A fecal sample (to assess gut microbiota composition and perform metabolomic analyses) will be collected between the screening visit and the first experimental session.

Peripheral sensitization session

Intervention Type OTHER

The extent of neurogenic inflammation induced by topical capsaicin will be used as a measure of the susceptibility to sensitize at peripheral level. A solution of capsaicin will be applied to the skin of the left or right volar forearm for 30 minutes. The capsaicin-induced neurogenic inflammation can be quantified by assessing the intensity, extent and duration of the capsaicin-induced cutaneous flare response using thermal infrared imaging. Using heat stimuli delivered to the treated skin and surrounding skin, the intensity and duration of the capsaicin-induced hyperalgesia will also be assessed. The experimental session will last approximately two hours.

Central sensitization session

Intervention Type OTHER

The extent of secondary mechanical hyperalgesia induced by high-frequency electrical stimulation (HFS) of the skin of the left or right volar forearm will be used as a measure of the susceptibility to develop central sensitization. The stimulation will be delivered using a multi-pin electrode designed to preferentially activate epidermal free nerve endings. The strength, spatial extent and duration of the HFS-induced changes in pinprick sensitivity will be characterized by using calibrated mechanical pinprick stimuli. The experimental session will last approximately one hour.

Session 1 : Central Session (right) - session 2 Peripheral Session (left)

The susceptibility to develop central sensitization will be assessed at the first experimental session, the stimulation will occur at the right forearm.

The susceptibility to develop peripheral sensitization will be assessed at the second experimental session, the stimulation will occur at the left forearm.

In both experimental sessions, participants will have to fill questionnaires about the use of medications, the Stanford Sleepiness Scale, the Leeds Sleep Evaluation Questionnaire, and the first part of the State and Trait Anxiety Questionnaire. During sensory stimulation, an infrared camera will be used to measure pupil diameter which constitute an indirect correlate of stimulus-evoked phasic variations in activity of the locus coeruleus. In order to measure autonomic reactivity to pain stimuli, the heart rate variability will be measured by recording electrocardiography.

Group Type OTHER

Screening visit

Intervention Type OTHER

The participants will be screened for inclusion and exclusion criteria and will be asked to fill the following questionnaires : Pittsburgh Sleep Quality Index, State and Trait Anxiety Questionnaire, Pain Catastrophizing Scale Fear of Pain Questionnaire, Perceived Stress Scale, Beck Depression Inventory, and questionnaires to assess their health status and the use of medications. A blood sample (to measure pro- and anti-inflammatory cytokines and perform metabolomic analyses) will be obtained. Enrolled participants will be given a wearable actimeter to assess daily total sleep duration during one week before the first experimental session. They will also be requested to complete daily a sleep diary during one week before each experimental session, and a food diary before the first experimental session. A fecal sample (to assess gut microbiota composition and perform metabolomic analyses) will be collected between the screening visit and the first experimental session.

Peripheral sensitization session

Intervention Type OTHER

The extent of neurogenic inflammation induced by topical capsaicin will be used as a measure of the susceptibility to sensitize at peripheral level. A solution of capsaicin will be applied to the skin of the left or right volar forearm for 30 minutes. The capsaicin-induced neurogenic inflammation can be quantified by assessing the intensity, extent and duration of the capsaicin-induced cutaneous flare response using thermal infrared imaging. Using heat stimuli delivered to the treated skin and surrounding skin, the intensity and duration of the capsaicin-induced hyperalgesia will also be assessed. The experimental session will last approximately two hours.

Central sensitization session

Intervention Type OTHER

The extent of secondary mechanical hyperalgesia induced by high-frequency electrical stimulation (HFS) of the skin of the left or right volar forearm will be used as a measure of the susceptibility to develop central sensitization. The stimulation will be delivered using a multi-pin electrode designed to preferentially activate epidermal free nerve endings. The strength, spatial extent and duration of the HFS-induced changes in pinprick sensitivity will be characterized by using calibrated mechanical pinprick stimuli. The experimental session will last approximately one hour.

Interventions

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Screening visit

The participants will be screened for inclusion and exclusion criteria and will be asked to fill the following questionnaires : Pittsburgh Sleep Quality Index, State and Trait Anxiety Questionnaire, Pain Catastrophizing Scale Fear of Pain Questionnaire, Perceived Stress Scale, Beck Depression Inventory, and questionnaires to assess their health status and the use of medications. A blood sample (to measure pro- and anti-inflammatory cytokines and perform metabolomic analyses) will be obtained. Enrolled participants will be given a wearable actimeter to assess daily total sleep duration during one week before the first experimental session. They will also be requested to complete daily a sleep diary during one week before each experimental session, and a food diary before the first experimental session. A fecal sample (to assess gut microbiota composition and perform metabolomic analyses) will be collected between the screening visit and the first experimental session.

Intervention Type OTHER

Peripheral sensitization session

The extent of neurogenic inflammation induced by topical capsaicin will be used as a measure of the susceptibility to sensitize at peripheral level. A solution of capsaicin will be applied to the skin of the left or right volar forearm for 30 minutes. The capsaicin-induced neurogenic inflammation can be quantified by assessing the intensity, extent and duration of the capsaicin-induced cutaneous flare response using thermal infrared imaging. Using heat stimuli delivered to the treated skin and surrounding skin, the intensity and duration of the capsaicin-induced hyperalgesia will also be assessed. The experimental session will last approximately two hours.

Intervention Type OTHER

Central sensitization session

The extent of secondary mechanical hyperalgesia induced by high-frequency electrical stimulation (HFS) of the skin of the left or right volar forearm will be used as a measure of the susceptibility to develop central sensitization. The stimulation will be delivered using a multi-pin electrode designed to preferentially activate epidermal free nerve endings. The strength, spatial extent and duration of the HFS-induced changes in pinprick sensitivity will be characterized by using calibrated mechanical pinprick stimuli. The experimental session will last approximately one hour.

Intervention Type OTHER

Eligibility Criteria

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Inclusion Criteria

* Aged between 18 and 65 years
* Ability to provide written informed consent
* Understanding French

Exclusion Criteria

* Current or recent (\< 2 months) use of antibiotics, probiotics, fiber supplements or any other molecule that modifies intestinal transit.
* Current or recent (\< 1 month) use of non-steroidal anti-inflammatory drugs and glucocorticoids
* Not willing or able to abstain from acute alcohol intoxication from 7 days prior to each of the two study sessions.
* Consumption of alcohol 24 hours prior to each of the two study sessions.
* Consumption of hypnotics, centrally-acting analgesics or psychotropic drugs.
* Obesity: body mass index \> 30 kg.m-2
* Pregnancy and breast-feeding
* Diabetes
* Cancer
* History of inflammatory bowel disease
* History of weight-loss surgery (e.g., gastric bypass, gastric band)
* History of autoimmune disease (e.g., lupus, rheumatoid arthritis)
* Evidence for any other clinically significant disease on direct questioning.
* Being a volleyball player due to risk of modified sensitivity of the volar forearm skin.
* Any implanted medical device such as cardiac pacemakers, cochlear implants and medication pumps.
* Dermatological condition affecting the skin of the volar forearms.
* History of an allergy to chili peppers/capsaicin.
* Any other reason to exclude the subject according to judgment by the investigator.
Minimum Eligible Age

18 Years

Maximum Eligible Age

65 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

Yes

Sponsors

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Université Catholique de Louvain

OTHER

Sponsor Role lead

Responsible Party

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Responsibility Role SPONSOR

Principal Investigators

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André Mouraux, MD, PhD

Role: PRINCIPAL_INVESTIGATOR

UCLouvain, IONS

Locations

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UCLouvain, IONS

Woluwe-Saint-Lambert, , Belgium

Site Status RECRUITING

Countries

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Belgium

Central Contacts

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Gwenaëlle Mievis, PhD Student

Role: CONTACT

+32488451915

Facility Contacts

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André Mouraux, MD, PhD

Role: primary

Gwenaëlle Mievis, PhD Student

Role: backup

Other Identifiers

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PAIN,SLEEP,MICROBIOTA

Identifier Type: -

Identifier Source: org_study_id

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