Decoding Mechanisms of Pain Modulation (HypnoPain)

Decoding Mechanisms of Pain Modulation Through Hypnosis and Vagus Nerve Stimulation

The main objective of this experimental trial is to gain further insights into the mechanisms of pain modulation, and more specifically, whether expectations of coping is one of the involved mechanisms. This will be investigated by comparing two different interventions known to influence pain perception; hypnosis and non-invasive stimulation of the vagus nerve, prior to a pain exposure task (hand immersion in cold water). Expectations will be assessed both pre- and post intervention.

Study Overview

• Status: Completed
• Conditions: Pain, Acute
• Intervention / Treatment: Behavioral: Hypnosis; Device: Vagus nerve stimulation; Device: Sham control

Detailed Description

Pain is a subjective experience, influenced by biological, psychological and social factors. This multidimensional view of pain has led to various efforts to affect people's pain experience. Nonpharmacological interventions, such as hypnosis, have proven successful in reducing pain whilst providing few, if any, negative side effects. Hypnosis involves a state of highly focused attention, with a constriction in peripheral awareness and a heightened responsiveness to social cues. This particular state can exert a powerful influence on the mind and body, yet the mechanisms responsible for this effect remains to a large degree unknown. The aim of this study is to investigate the effect of hypnosis given prior to a painful procedure (cold pressor test, CPT), to investigate the effect on pain perception and tolerance, but most importantly, to investigate if the effect is mediated by a change in expectations of coping. Previous studies have provided support for the the effect of hypnosis on expectations, but they have focused exclusively on stimulus expectancies (expectations of pain intensity), while the current study will focus on response outcome expectancies (expectations of coping) in line with the Cognitive Activation Theory of Stress (CATS).

Whilst hypnosis may dampen the stress response through expectancies (top-down), another way of dampening the stress response is through transcutaneous vagus nerve stimulation (tVNS) (bottom-up). Vagus nerve stimulation is proposed as another nonopioid pain treatment with minimal side effects. The vagus nerve is the 10th cranial nerve, connecting the viscera and the brain and influencing multiple systems of the body including the cardiac, immunologic, and endocrine system, and the activity of many visceral organs. This makes the vagus nerve a possibly important mediating (transmitting) and modulating nerve of pain signals . Stimulation of the vagus nerve is believed to modulate pain by inhibiting inflammation, oxidative stress, and sympathetic activity, and possibly also by inducing a brain activation pattern that may be incongruent with the pain matrix (i.e. brain regions commonly active during pain). VNS might also mediate the effects of the opioid system in pain modulation. These mechanisms have in common that they are hypothesized to affect neuronal hyperexcitability, resulting in a reduced pain perception, which is supported by experimental animal studies.

• Study Type: Interventional
• Enrollment (Actual): 156
• Phase: Not Applicable

Contacts and Locations

Study Locations

• Norway
  • Oslo, Norway
    • University of Oslo

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 70 years (Adult, Older Adult)
• Accepts Healthy Volunteers: Yes

Description

Inclusion Criteria:

• Adults aged 18-70 years
• Fluent Norwegian language skills

Exclusion Criteria:

• History of cardiovascular disease
• Chronic pain conditions (any diagnoses resulting in chronic pain)

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Triple

Number of Arms

3

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Hypnosis; A brief hypnosis session will be provided to participants in this arm prior to immersion in the cold water.	Behavioral: Hypnosis; The hypnosis will be conducted by clinical psychologists who have the formal competence and training in hypnosis. We will be using a tailored hypnosis script designed for this particular study, with a duration of 10-15 minutes. The script involves a hypnotic induction (relaxation-based), imagery (suggestions for pleasant visual imagery), a deepening procedure, and symptom-specific suggestions. The introduction begins by having the hypnotist debunk many of the common myths and misconceptions that patients may hold about hypnosis, and provide a description of hypnosis. Hypnosis is described as focused attention and concentration - like being so lost in a book or movie that it is easy to lose track of what is going on around you. Once the patient is deeply hypnotized, the therapist offers suggestions to reduce distress and improve pain tolerance.
Experimental: Active tVNS; Participants in the active tVNS condition will receive electronic stimulation of the vagus nerve prior to immersion in the cold water.	Device: Vagus nerve stimulation; A CE approved tVNS device will be used to stimulate the afferent auricular branch of the vagus nerve located medial of the tragus at the entry of the acoustic meatus [36]. A standardized intensity of 10 mA with a pulse width of 250 μs and a consistent stimulation frequency of 25 Hz will be used for optimal stimulation. The stimulation will constantly alternate between active stimulation for 30 seconds, followed by a break of 30 seconds [37], and will have a duration of 15 minutes. Active tVNS is performed in a relaxed position, sitting back in a chair no more than 30 degrees from the horizontal, with both feet flat on the floor, and hands on thighs with palms facing downward. The bipolar stimulation electrode is placed correctly within the concha of the left ear. Participants are instructed to breathe normally while not talking or making any movements during their session.
Sham Comparator: Sham tVNS; Participants in the sham tVNS will receive the electrode similar to the active treatment, but no stimulation will be performed.	Device: Sham control; Sham tVNS is performed in a relaxed position, sitting back in a chair no more than 30 degrees from the horizontal, with both feet flat on the floor, and hands on thighs with palms facing upward. The bipolar stimulation electrode is placed correctly within the concha of the left ear, but no actual stimulation will be performed. The electrode will be left on for 15 minutes. Participants are instructed to breathe normally while not talking or making any movements during their session

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Pain tolerance	Time elapsed before removing the hand from the water.	up to 10 minutes (During exposure (hand immersion in cold water))

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Pain intensity	rated on a NRS 0-10 where 0 is "no pain" and 10 is "the worst pain imaginable"	Immediately after the cold pressor test
Pain bothersomeness	NRS 0-10 where 0 is "not bothersome at all" and 10 is "the most bothersome imaginable"	Immediately after the cold pressor test

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
Expectancies of coping	NRS 0-10: "To what degree do you expect to cope with the painful procedure?"	Within 5 minutes pre- and within 5 minutes post intervention
Expectancies of coping: pre-conscious	The Function Acquisition Speed Test, linking verbal associations involving the painful procedure (CPT) and coping concordant and dis-concordant words	Within 5 minutes pre- and within 5 minutes post intervention

Collaborators and Investigators

• Sponsor: University of Oslo

Publications and helpful links

Helpful Links

• Related Info

Study record dates

Study Major Dates

• Study Start (Actual): August 1, 2022
• Primary Completion (Actual): November 17, 2023
• Study Completion (Actual): November 17, 2023

Study Registration Dates

• First Submitted: April 12, 2022
• First Submitted That Met QC Criteria: April 19, 2022
• First Posted (Actual): April 20, 2022

Study Record Updates

• Last Update Posted (Actual): December 4, 2023
• Last Update Submitted That Met QC Criteria: December 1, 2023
• Last Verified: December 1, 2023

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Pain; Neurologic Manifestations; Acute Pain
• Other Study ID Numbers: 409472

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES
• IPD Plan Description: We plan to share the study protocol, README files as well the statistical codes for the main analysis in an open repository (e.g. Open Science Framework) to ensure transparency and reproducability.
• IPD Sharing Time Frame: As soon as possible
• IPD Sharing Access Criteria: Openly accessible
• IPD Sharing Supporting Information Type: STUDY_PROTOCOL; SAP; ICF; ANALYTIC_CODE

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: Yes