Decoding Mechanisms of Pain Modulation

Not Applicable

Completed

• Conditions: Pain, Acute
• Interventions: Device: Sham control; Behavioral: Hypnosis; Device: Vagus nerve stimulation

• Registration Number: NCT05336370
• Lead Sponsor: University of Oslo

Brief Summary

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.

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 Timeline

• Study First Submitted: 2022-04-12
• Study First Submitted QC: 2022-04-19
• Study First Posted: 2022-04-20
• Study Start: 2022-08-01
• Primary Completion: 2023-11-17
• Study Completion: 2023-11-17
• Status Verified: 2023-12
• Last Update Submitted: 2023-12-01
• Last Update Posted: 2023-12-04

Recruitment & Eligibility

• Status: COMPLETED
• Sex: All
• Target Recruitment: 156

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 & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Sham tVNS	Sham control	Participants in the sham tVNS will receive the electrode similar to the active treatment, but no stimulation will be performed.
Hypnosis	Hypnosis	A brief hypnosis session will be provided to participants in this arm prior to immersion in the cold water.
Active tVNS	Vagus nerve stimulation	Participants in the active tVNS condition will receive electronic stimulation of the vagus nerve prior to immersion in the cold water.

Primary Outcome Measures

Name	Time	Method
Pain tolerance	up to 10 minutes (During exposure (hand immersion in cold water))	Time elapsed before removing the hand from the water.

Secondary Outcome Measures

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

Trial Locations

Locations (1)

University of Oslo; 🇳🇴 Oslo, Norway