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

NCT06983678 | Recruiting

• 2 other identifiers: Pro001177591R01DA060859-01A1
• Study Type: interventional
• Target: 132
• Locations: 1 country
• Sites: 1

Brief Summary

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.

Conditions

Tobacco Use; Chronic Pain

Outcome Measures

Primary Outcomes (8)

• Pain intensity ratings to high heat vs neutral temperatures

  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.

  Measured at each fMRI session (up to 1.5 hours)

• Activation of the inferior frontal gyrus (IFG)

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

  Measured at each fMRI session (up to 1.5 hours)

• Resting state functional connectivity with the IFG

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

  Measured at each fMRI session (up to 1.5 hours)

• Time to lapse

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

  Measured daily during the 1-week abstinence test

• Daily pain ratings

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

  Measured with daily EMA prompts for 10 days

• Daily withdrawal symptoms

  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

  Measured with daily EMA prompts for 10 days

• Fluctuations in pain ratings vs smoking urge

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

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

• Fluctuations in pain ratings vs number of cigarettes smoked

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

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

Study Arms (4)

Participants with chronic pain - Smoking as usual fMRI session first followed by Abstinent fMRI

EXPERIMENTAL

Participants with chronic pain randomized to complete a smoking as usual fMRI session followed by an Abstinent fMRI session.

Behavioral: Smoking as usual fMRI session; Behavioral: Abstinent fMRI session

Participants with chronic pain - Abstinent fMRI session first followed by Smoking as usual fMRI

EXPERIMENTAL

Participants with chronic pain randomized to complete an Abstinent fMRI session followed by a smoking as usual fMRI session.

Behavioral: Smoking as usual fMRI session; Behavioral: Abstinent fMRI session

Participants without chronic pain - Smoking as usual fMRI session first followed by Abstinent fMRI

EXPERIMENTAL

Participants without chronic pain randomized to complete a smoking as usual fMRI session followed by an Abstinent fMRI session.

Behavioral: Smoking as usual fMRI session; Behavioral: Abstinent fMRI session

Participants without chronic pain - Abstinent fMRI session first followed by Smoking as usual fMRI

EXPERIMENTAL

Participants without chronic pain randomized to complete an Abstinent fMRI session followed by a smoking as usual fMRI session.

Behavioral: Smoking as usual fMRI session; Behavioral: Abstinent fMRI session

Interventions

Smoking as usual fMRI session BEHAVIORAL

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

Participants with chronic pain - Abstinent fMRI session first followed by Smoking as usual fMRI; Participants with chronic pain - Smoking as usual fMRI session first followed by Abstinent fMRI; Participants without chronic pain - Abstinent fMRI session first followed by Smoking as usual fMRI; Participants without chronic pain - Smoking as usual fMRI session first followed by Abstinent fMRI

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

Participants with chronic pain - Abstinent fMRI session first followed by Smoking as usual fMRI; Participants with chronic pain - Smoking as usual fMRI session first followed by Abstinent fMRI; Participants without chronic pain - Abstinent fMRI session first followed by Smoking as usual fMRI; Participants without chronic pain - Smoking as usual fMRI session first followed by Abstinent fMRI

Eligibility Criteria

• Age: 21 Years - 65 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• 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;

Sponsors & Collaborators

• Duke University: lead
• National Institute on Drug Abuse (NIDA): collaborator

Study Sites (1)

Duke North Pavilion

Durham, North Carolina, 27705, United States

RECRUITING

MeSH Terms

Conditions

Tobacco Use; Chronic Pain

Interventions

Smoking Devices

Condition Hierarchy (Ancestors)

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

Intervention Hierarchy (Ancestors)

Manufactured Materials; Technology, Industry, and Agriculture

Study Officials

• Maggie Sweitzer, Ph.D.

  Duke University

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Clinical Research Coordinator

CONTACT

919-907-9955; sweitzerlab@duke.edu

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: BASIC SCIENCE
• Intervention Model: CROSSOVER
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: May 14, 2025
• First Posted: May 21, 2025
• Study Start: November 4, 2025
• Primary Completion (Estimated): March 31, 2030
• Study Completion (Estimated): March 31, 2030
• Last Updated: November 20, 2025

Record last verified: 2025-11

Data Sharing

• IPD Sharing: Will not share

Locations

US (1)