Decoding Mechanisms of Pain Modulation
Condition: Pain, Acute
MeSH terms: Acute Pain
Study type: Interventional

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.
    

Intervention name(s): Hypnosis; Vagus nerve stimulation; Sham control
Intervention type(s): Behavioral; Device; Device
Intervention description(s): 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.; 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 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
Allocation: Randomized
Intervention model: Parallel Assignment
Intervention model description: The HypnoPain trial is designed as an experimental randomized controlled, statistician blinded superiority trial with three parallel groups
Masking: Triple (Participant, Investigator, Outcomes Assessor)
Primary purpose: Treatment