Overview

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.

Eligibility

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.