Pain-related Fear as a Facilitator of Nocebo Hyperalgesia

Summary

Nocebo hyperalgesia is characterized by adverse pain outcomes, induced by patients' expectations. In the lab, nocebo effects are commonly studied via classical conditioning, a method that employs pairings of neutral cues/treatments with different pain intensities to install differential pain-related expectations. In such conditioning experiments, participants are typically taught that a (sham) treatment exaggerates their pain, by surreptitiously administering high intensity (e.g. pain) stimuli in combination with this treatment. Verbal suggestions are also often used to inform participants of the supposed adverse effects of such treatments. In nocebo studies, higher pain levels and suggestions that are of more threatening nature may induce fear, thereby adding a crucial element to the experimental manipulation. Since nocebo effects are hypothesized to arise in clinical settings due to a combination of several psychological and cognitive mechanisms, it is important to study the role that factors such as higher pain levels, conditioned pain-related fear, or more threatening verbal suggestions may play in the formation of nocebo hyperalgesia. To date, no studies have focused on the fear-inducing effect that different pain intensities or verbal threat suggestions may have and how this fear, in turn, may strengthen the acquisition of nocebo effects. This study aims to investigate whether higher pain intensity or higher pain-related fear induced via threatening suggestions facilitate the acquisition and hinder subsequent extinction of nocebo hyperalgesia. This study will be conducted at Leiden University.

Conditions

• Hyperalgesia
• Chronic Pain Syndrome
• Chronic Pain, Psychogenic
• Fear of Pain

Interventions

BEHAVIORAL

Threat manipulation (control, no threat)

Before the start of conditioning, a mock skin-sensitivity test informs participants that their skin reacts to heat normally and it is safe for them to participate. A skin-sensitivity reading shows participants a scale that is in the green (no danger) zone.

BEHAVIORAL

Threat manipulation

Before the start of conditioning, a mock skin-sensitivity test informs participants that their skin is very sensitive and their nerve fibers are very responsive and they may have adverse reactions to the heat-pain application. A skin-sensitivity reading shows participants a scale that is in the red (higher danger) zone.

BEHAVIORAL

Conditioning of moderate pain

During nocebo trials of the acquisition phase, conditioned stimuli (i.e., on-screen visual cues "ON" signaling the activation of sham electrical stimulation) are paired to unconditioned moderate-pain stimuli, to induce a negative association between the activation of electrical stimuli and an increase in pain. During control trials of the acquisition phase, the deactivation of the sham electrical stimulation (i.e., on-screen message "OFF") is paired to 'baseline' pain of lower intensity.

BEHAVIORAL

Conditioning of high pain

During nocebo trials of the acquisition phase, conditioned stimuli (i.e., on-screen visual cues "ON" signaling the activation of sham electrical stimulation) are paired to unconditioned high-pain stimuli, to induce a negative association between the activation of electrical stimuli and an increase in pain. During control trials of the acquisition phase, the deactivation of the sham electrical stimulation (i.e., on-screen message "OFF") is paired to pain of lower intensity.

BEHAVIORAL

Extinction

During extinction, the previously conditioned nocebo effects on pain are attenuated by pairing the nocebo and control visual cues (i.e., on-screen messages "ON" and "OFF") to pain stimuli of only lower intensity.

Sponsors & Collaborators

• Universiteit Leiden

  collaborator OTHER

• KU Leuven

  collaborator OTHER

• Maastricht University

  collaborator OTHER

• Leiden University Medical Center

  lead OTHER

Principal Investigators

• Andrea WM Evers · Leiden University Medical Center

Study Design

Allocation

RANDOMIZED

Purpose

BASIC_SCIENCE

Masking

SINGLE

Model

PARALLEL

Eligibility

Min Age

17 Years

Max Age

35 Years

Sex

ALL

Healthy Volunteers

Yes

Timeline & Regulatory

Start

2019-10-14

Primary Completion

2020-02-14

Completion

2020-02-14

Countries

• Netherlands

Study Locations