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NCT Number: NCT06983678

Neural Correlates and Behavioral Impact of Withdrawal-induced Hyperalgesia Among People Who Smoke With and Without Chronic Pain

Individuals with chronic pain are more likely to smoke cigarettes and have more difficulty quitting smoking than the general population, in part because withdrawal from smoking can lead to temporary increases in pain. This research will examine how smoking withdrawal changes the way the brain processes pain, and whether these withdrawal-related changes interfere with the ability to stop smoking. The results of this research will provide important information that can be used to guide the development of interventions to help people with chronic pain who smoke cigarettes to quit smoking and improve their health.

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Key information

Conditions

Tobacco Use Behavior Chronic Pain Neurologic Manifestations Pain Pathological Conditions, Signs and Symptoms Signs and Symptoms

Age range

21 year–65 year

Sex eligibility

All sexes

Study type

Interventional

Phase

Not applicable

Primary location

Duke North Pavilion

Durham, North Carolina, 27705, United States

Location status: Recruiting

Location contact

Clinical Research Coordinator

CONTACT

[email protected]

984-209-9816

About this study

Eligible participants will complete an initial in-person screening session in which eligibility is confirmed and baseline pain and smoking measures are collected, followed by a sensory testing and training session, in which participants are introduced to the mock MRI scanner and familiarized with the thermal pain stimulation and psychophysiological rating procedures. Participants will then complete two fMRI sessions using a within-subjects, crossover design, with one scan following 24-hrs abstinence from smoking, and the other following smoking as usual. Both fMRI sessions will be identical other than the smoking instructions prior to the scan. During each scan, participants will complete experience and provide ratings to painful heat stimuli. Before and after scanning, participants will complete measures of craving, withdrawal, and current pain level. After completion of the scanning sessions, participants will return to the lab for a baseline visit prior to beginning the abstinence test. During that session, they will have software installed on their smartphone for ecological momentary assessment (EMA), and they will be trained in the procedures for biochemical verification of abstinence. They will then complete 3 days of baseline EMA, during which participants are prompted at 5 random times throughout the day, and once in the evening, to answer questions about their pain, smoking urge, and recent smoking. They will then continue EMA while attempting to abstain from smoking during the 1-week abstinence test. During the abstinence test, each day of abstinence is reinforced with money using a descending schedule. Participants will provide breath samples over video during this week using equipment provided by the lab in order to verify abstinence from smoking. At the conclusion of the study, participants will return to the lab for a final visit to return all equipment.

Who can participate

Healthy volunteers accepted: No

Only the study team can determine whether someone qualifies for participation.

Inclusion criteria

  • History of chronic non-cancer low back pain with duration ≥ 6 months OR no history of chronic pain;
  • age 21-65;
  • smoking of at least 10 cig/day for > 2 years;
  • have an iPhone or Android smartphone capable of running the EMA software

Exclusion criteria

  • pain complaint specifically due to cancer, rheumatoid arthritis, or complex regional pain syndrome;
  • actively taking steps to quit smoking;
  • inability to attend all required experimental sessions;
  • significant health problems, such as chronic hypertension, emphysema, seizure disorder, history of significant heart problems;
  • conditions that would make MRI scanning unsafe (e.g., metal implants, claustrophobia)
  • use of opioids within the past 90 days
  • past year alcohol or substance use disorder
  • positive urine test for illegal drugs (other than marijuana);
  • daily use of alcohol or marijuana;
  • lifetime history of psychotic disorder, or current unstable psychiatric disorder;
  • regular use of non-cigarette tobacco products or electronic cigarettes;
  • major surgery within the past 6 months or planned surgery within the timeframe of the study;
  • breath alcohol level > 0.0 (participants failing for BAL will be allowed to rescreen once);
  • recently quit smoking for > 3 days;
  • pregnancy or planning to become pregnant;
  • any factors that at the discretion of the investigators would adversely affect the participant or integrity of the study (e.g., ongoing legal action or disability claim regarding pain, uncontrolled psychiatric disorder, head/neck injury, use of certain medications)

Treatment and study plan

Smoking as usual fMRI session

Behavioral

Participants in this condition will continue smoking as usual prior to the fMRI session

Abstinent fMRI session

Behavioral

Participants in this condition will be asked to abstain from smoking or using any other tobacco products for 24 hours prior to the fMRI session

Primary outcomes

  1. Pain intensity ratings to high heat vs neutral temperatures

    Time frame: Measured at each fMRI session (up to 1.5 hours)

    Participants will rate their current pain intensity following each of the heat stimulus blocks during the fMRI scans. Pain intensity is measured on a 0-10 visual analogue scale, with higher scores indicating greater pain.

  2. Activation of the inferior frontal gyrus (IFG)

    Time frame: Measured at each fMRI session (up to 1.5 hours)

    % signal change in response to the contrast of high heat vs rest will be extracted from right and left IFG

  3. Resting state functional connectivity with the IFG

    Time frame: Measured at each fMRI session (up to 1.5 hours)

    Fisher-Z transformed correlation maps of connectivity with the IFG will be evaluated within a subcortical mask including the caudate and thalamus

  4. Time to lapse

    Time frame: Measured daily during the 1-week abstinence test

    The number of days of continuous, biochemically verified abstinence prior to smoking

  5. Daily pain ratings

    Time frame: Measured with daily EMA prompts for 10 days

    Mean pain ratings during the initial days of abstinence will be examined as a function of chronic pain status, assessed at baseline

  6. Daily withdrawal symptoms

    Time frame: Measured with daily EMA prompts for 10 days

    Daily withdrawal symptoms will be assessed over EMA using the Minnesota Smoking Withdrawal Scale. Mean withdrawal symptoms during the initial days of abstinence will be examined as a function of chronic pain status, assessed at baseline

  7. Fluctuations in pain ratings vs smoking urge

    Time frame: Measured 5 times per day with random EMA prompts for 10 days

    Fluctuations in pain ratings will be examined to determine their association with level of smoking urge

  8. Fluctuations in pain ratings vs number of cigarettes smoked

    Time frame: Measured 5 times per day with random EMA prompts for 10 days

    Fluctuations in pain ratings will be examined to determine their association with number of cigarettes smoked between each assessment.

Study contacts

Contact information is provided by the study sponsor or research team.

Clinical Research Coordinator

CONTACT

[email protected]

919-907-9955

Sponsors and collaborators

Lead sponsor

Duke University

Other

Collaborators

  • National Institute on Drug Abuse (NIDA)

Registry information

Acronym: PRISM02

Important dates

Study start
2025
Primary completion
2030
Study completion
2030
First posted
May 21, 2025
Registry last updated
Nov 20, 2025

OpenTrials presents study information sourced from ClinicalTrials.gov. The official registry record should be consulted for the latest information.

View the official ClinicalTrials.gov record (opens in a new tab)

This listing is for discovery and informational purposes only. It is not medical advice, does not guarantee that a study is recruiting, and does not determine eligibility. Contact the study team and a qualified healthcare professional when considering participation.

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