Increased Emotional-motivational Processing in Patients with Chronic Pain and Its Neural Correlates

NCT05257356 | Completed DMC

• 1 other identifier: P000PS_203872/1
• Study Type: interventional
• Target: 138
• Locations: 1 country
• Sites: 1

Brief Summary

Chronic pain causes immense suffering and reductions in quality of life as well as enormous socioeconomic costs. Very many chronic pain patients fall into the category of unspecific pain, i.e. pain without clear medical explanation, with lacking effective treatments. It is assumed that a negative hedonic shift, characterized by excessive emotional-motivational processing and neg-ative affect, contributes causally to the development and maintenance of chronic pain. The mechanisms leading to such a shift are largely unclear; however, learning mechanisms appear likely candidates, possibly causing decreased connectivity in the fronto-striatal brain circuits. The project's over-all aim is to characterize mechanisms of emotional-motivational pain pro-cessing. The specific objectives are to illustrate that emotional-motivational pain components are heightened in chronic pain and that they can be de-creased by counterconditioning as an important and pervasive mechanisms in everyday life. Furthermore, its neural correlates in fronto-striatal networks underlying the conditioning effects will be characterized.

Conditions

Chronic Pain; Low Back Pain

Keywords

pain; chronic pain; emotional-motivational pain components; counterconditioning; negative hedonic shift

Outcome Measures

Primary Outcomes (2)

• Successful Avoidance Responses

  In Substudy1(b) and Substudy2: The number of successful avoidance responses upon correct discrimination responses in the task assessing sensory-discriminative and emotional-motivational pain responses simultaneously.

  during the procedure

• Fronto-striatal Networks

  In Substudy 2: Blood oxygen level dependent (BOLD) signal and changes in functional connectivity in fronto-striatal networks while assessing sesnorydiscriminative and emotional-motivational pain responses simultaneously.

  during the procedure

Secondary Outcomes (15)

• Reaction Times (RT)

  during the procedure

• Pain Threshold in °C

  baseline

• Pain Tolerance in °C

  baseline

• Visual Analogue Scale (VAS) for Perceived Pain Intensity

  during the procedure

• Visual Analogue Scale (VAS) for Perceived Pain Unpleasantness

  during the procedure

Study Arms (2)

Chronic Pain Patients

EXPERIMENTAL

All participants perform 1 psychophysical task to assess sensory-discriminative and emotional-motivational pain responses simultaneously. The performance of chronic pain patients will be compared to healthy volunteers to characterize possible alterations in patients. Associative learning by monetary reinforcement will be implemented to diminish the aversiveness of pain, which is assumed to be already increased in patients. Primary objectives: Show that emotional-motivational components are increased relative to sensory-discriminative components in chronic pain, and that enhanced emotional-motivational pain responses in chronic pain can be decreased by counterconditioning, leading to a normalization of pain perception relative to healthy individuals. Secondary objective: Assess whether chosen personality traits assessed by questionnaires can explain variations in sensory-discriminative and emotional-motivational pain responses.

Behavioral: psychophysical tasks

Healthy Controls

EXPERIMENTAL

Substudy 1(b): Participants perform 1 psychophysical task to assess sensory-discriminative and emotional-motivational pain responses simultaneously. Associative learning by monetary reinforcement is implemented to diminish the pain aversiveness. Substudy2: Participants perform the same task combined with MRI assessing the counterconditioning effects on frontostriatal circuits. Primary objective: Show that emotional-motivational components are increased relative to sensory-discriminative components in chronic pain (Substudy 1(b)). Assess the neural correlates of the counterconditioning effects on emotional-motivational pain responses, specifically alterations in functional connectivity in frontostriatal networks compared to the unchanged natural state (Substudy 2). Secondary objective: To assess whether chosen personality traits assessed by questionnaires can explain variations in sensory-discriminative and emotional-motivational pain responses (Substudy1(b)+2).

Behavioral: psychophysical tasks

Interventions

psychophysical tasks BEHAVIORAL

Substudy 1(b): All participants will perform one psychophysical task to assess sensory-discriminative and emotional-motivational pain responses simultaneously. The responses and the reaction times of chronic pain patients will be compared to those of healthy participants to characterize possible alterations in the patients (Substudy 1). Associative learning by monetary reinforcement will be implemented to diminish the aversiveness of the pain, which is assumed to be already increased in the patients. Substudy 2: As in Substudy 1, all participants will perform one psychophysical task to assess sensory-discriminative and emotional-motivational pain responses simultaneously combined with MRI assessing the effects of the counterconditioning on fronto-striatal circuits.

Chronic Pain Patients; Healthy Controls

Eligibility Criteria

• Age: 18 Years - 70 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Between 18 and 70 years of age (in Substudy 1: age- and sex-matched to chronic pain patients)
• Good overall health status
• Sufficient knowledge of German or English to follow instructions
• Ability to give written informed consent

You may not qualify if:

• Pain longer than \>3 consecutive days and on more than 30 days within the last 12 months
• Major psychiatric or neurological disorders, and substance abuse
• Consumption of alcohol, illegal drugs, and analgesic drugs within 24 hours before testing
• Pregnancy
• For Substudy 2: An MR-specific safety questionnaire will be filled in to check for any contradiction to magnetic resonance imaging (MRI): wearing an electronic device, implants or prosthetics, injury from metal parts or fragments, metal parts in or on the body, surgery on the head, heart or back, tattoo or permanent makeup, problems lying still for long periods of time, claustrophobia, possible pregnancy, metal contraceptive coil
• CHRONIC PAIN PATIENTS
• Between 18 and 70 years of age
• Unspecific musculoskeletal pain as defined according to the ICD-11 as chronic primary pain (MG30.1, e.g. chronic widespread pain, complex regional pain syndrome, chronic primary headache or orofacial pain, chronic migraine, chronic tension-type headache, trigeminal autonomic cephalalgias, burning mouth syndrome, chronic primary visceral pain, irritable bowel syndrome, chronic primary musculoskeletal pain), and which is not classified as chronic cancer related pain (MG30.2; e.g. chronic cancer pain, chronic post-cancer treatment pain), chronic postsurgical or post traumatic pain (MG30.3; e.g. chronic postsurgical pain, chronic posttraumatic pain), chronic secondary musculoskeletal pain (MG30.4; e.g. chronic musculoskeletal pain from persistent inflammation, chronic musculoskeletal pain associated with structural changes, chronic musculoskeletal pain associated with a disease of the nervous system), chronic secondary visceral pain (MG30.5; e.g. chronic visceral pain from persistent inflammation, chronic visceral pain from vascular mechanisms, chronic visceral pain from mechanical factors), chronic neuropathic pain (MG30.6; e.g. chronic peripheral neuropathic pain, trigeminal neuralgia, postherpetic neuralgia, chronic central neuropathic pain), chronic secondary headache or orofacial pain (MG30.7; e.g. chronic dental pain, chronic neuropathic orofacial pain, trigeminal neuralgia, headache or orofacial pain attributed to chronic secondary temporo-mandibular disorders), other specified chronic pain (MG30.Y), or other non-specified chronic pain (MG30.Z)
• Sufficient knowledge of German or English to follow instructions
• Ability to give written informed consent
• Major psychiatric or neurological disorders, and substance abuse
• Regular intake of opioids for pain (e.g. burprenorphine, codeine, fentanyl, hydromorphone, orphine, oxycodone, tapentadol, tilidine/na-loxone, tramadol)
• Consumption of alcohol, illegal drugs, and analgesic drugs within 24 hours before testing
• Pregnancy

Sponsors & Collaborators

• susanne becker: lead
• SNSF: collaborator

Study Sites (1)

Balgrist Campus

Zurich, Canton of Zurich, 8008, Switzerland

Location

MeSH Terms

Conditions

Chronic Pain; Low Back Pain; Pain

Condition Hierarchy (Ancestors)

Neurologic Manifestations; Signs and Symptoms; Pathological Conditions, Signs and Symptoms; Back Pain

Study Officials

• Susanne Becker, Dr. Prof.

  Balgrist Universitätsklinik

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: RANDOMIZED
• Masking: SINGLE
• Who Masked: PARTICIPANT
• Masking Details: Participants are not fully instructed about the purpose before and during the test but will be debriefed after testing.
• Purpose: BASIC SCIENCE
• Intervention Model: CROSSOVER
• Sponsor Type: OTHER
• Responsible Party: SPONSOR INVESTIGATOR
• PI Title: Head of Research Group

Model Details: Substudy 1(b): All participants will perform one psychophysical task to assess sensory-discriminative and emotional-motivational pain responses simultaneously. The responses and the reaction times of chronic pain patients will be compared to those of healthy participants to characterize possible alterations in the patients. Associative learning by monetary reinforcement will be implemented to diminish the aversiveness of the pain, which is assumed to be already increased in the patients. Substudy 2: As in Substudy 1, all participants will perform one psychophysical task to assess sensory-discriminative and emotional-motivational pain responses simultaneously combined with MRI assessing the effects of the counterconditioning on fronto-striatal circuits.

Study Record Dates

• First Submitted: February 3, 2022
• First Posted: February 25, 2022
• Study Start: April 6, 2022
• Primary Completion: April 5, 2024
• Study Completion: April 5, 2024
• Last Updated: February 11, 2025

Record last verified: 2024-09

Data Sharing

• IPD Sharing: Will not share

Locations

CH (1)