A Randomized-controlled Clinical Trial of Hypnosis Versus Open Label Placebo for Chronic Neuropathic Pain With an Investigation of Neuro-cognitive Dysfunctions as Maintaining Factors and Therapeutic Targets

The current study, through two sub-studies, aims to investigate through clinical, psychophysical and biological methodology in a population of patients with chronic neuropathic pain (i.e. involving a peripheral or CNS lesion), A) signs of a maladaptive stress response, correlates of decreased pain modulation, and of cognitive impairment, B) test hypnosis vs. open label placebo as potential mechanistic treatments of these suspected maintaining factors.

Patients will be recruited at the CHUV's Pain Center and via collaborating physicians treating patients with neuropathic pain (general practitioner, neurologist…). Controls will be recruited via advertisements posted in public places such as the CHUV, or the University of Lausanne's website and compounds.

Participants will be informed, in a clear and comprehensible way, of the nature of the study, its purpose, the procedures involved, the expected duration, the potential risks and benefits and any discomfort it may entail.

Participants (patients and volunteers) will be first phone or live pre-screened by the study team to ensure they fulfil the inclusion criteria (except the MMSE). Then, eligible participants will be invited to the pain centre for the first study visit. During this visit informed will first be collected by the PI. Following this, a screening of the cognitive function of the participant will be performed through the MMSE test. Participants with a score lower than 24/30 will be excluded and informed of their exclusion and its cause. Pre-screening and/or screening data of non-included participants will be archived anonymously at the pain center in order to document the CONSORT diagram. All other consented participants will then take part in the first study procedures, which consist in a psychophysical assessment to determine their baseline performance. These will be compared between patients and matched volunteers without chronic pain, as well as longitudinally across treatment groups. This assessment lasts approximately 3h and includes physiological recording (cardiac rhythm, pulse-oxymetry, respiratory frequency), cognitive functions evaluation (Wisconsin cards sorting test, Trail Making Test, Complex Figure Copy) and questionnaires (Brief Pain Inventory, Hospital Anxiety and Depression Scale, Tampa Scale of Kinesiophobia, Pain Catastrophizing Scale, WHO-BREF quality of Life, Brief Resilience Scale, Pain coping, scale and sleep index). During this visit, patients will also undergo sensory testing to evaluate their abilities to modulate pain perception. Moderately painful 10s.heat stimuli will be applied on the forearm with a thermode (Medoc TSA, Israel). In pseudo-random order, participants are instructed to pay attention to the stimulus, vs. use distraction or focused mental imagery (i.e. reappraisal of the sensation). A peripheral blood plasma sample will also be collected for metabolomic analysis, in collaboration with the Metabolomics platform of the University of Lausanne. The day before the psychophysical assessment, participants will receive instructions for saliva collection in order to determine the variation of cortisol levels during the day (4 time points) and metabolomic signature. They will receive kits either directly or by mail. Participants will bring the samples along with them to the study visit.

Healthy volunteers will only participate in this unique visit. Patients will be randomized in equal proportions into the "Hypnosis", "Open Label Placebo" or the "treatment as usual" arm.