Clinical trial NCT06983678: Neural Correlates and Behavioral Impact of Withdrawal-induced Hyperalgesia Among People Who Smoke With and Without Chronic Pain
Official title: Neural Correlates and Behavioral Impact of Withdrawal-induced Hyperalgesia Among People Who Smoke With and Without Chronic Pain
Study type: INTERVENTIONAL
Overall status: NOT_YET_RECRUITING
Phase: NA
Conditions: Tobacco Use
Chronic Pain
Lead sponsor: Duke University
Sponsor class: OTHER
Collaborators: name: National Institute on Drug Abuse (NIDA)
First posted: 2025-05-21
Enrollment: 132
Sex: ALL
Minimum age (years): 21
Maximum age (years): 65
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: CROSSOVER
Primary purpose: BASIC_SCIENCE

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.

Detailed description: 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.

Eligibility criteria: Inclusion Criteria:

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

Exclusion Criteria:

1. pain complaint specifically due to cancer, rheumatoid arthritis, or complex regional pain syndrome;
2. actively taking steps to quit smoking;
3. inability to attend all required experimental sessions;
4. significant health problems, such as chronic hypertension, emphysema, seizure disorder, history of significant heart problems;
5. conditions that would make MRI scanning unsafe (e.g., metal implants, claustrophobia)
6. use of opioids within the past 90 days
7. past year alcohol or substance use disorder
8. positive urine test for illegal drugs (other than marijuana);
9. daily use of alcohol or marijuana;
10. lifetime history of psychotic disorder, or current unstable psychiatric disorder;
11. regular use of non-cigarette tobacco products or electronic cigarettes;
12. major surgery within the past 6 months or planned surgery within the timeframe of the study;
13. breath alcohol level \> 0.0 (participants failing for BAL will be allowed to rescreen once);
14. recently quit smoking for \> 3 days;
15. pregnancy or planning to become pregnant;
16. 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)

Primary outcomes:
measure: Pain intensity ratings to high heat vs neutral temperatures
timeFrame: Measured at each fMRI session (up to 1.5 hours)
measure: Activation of the inferior frontal gyrus (IFG)
timeFrame: Measured at each fMRI session (up to 1.5 hours)
measure: Resting state functional connectivity with the IFG
timeFrame: Measured at each fMRI session (up to 1.5 hours)
measure: Time to lapse
timeFrame: Measured daily during the 1-week abstinence test
measure: Daily pain ratings
timeFrame: Measured with daily EMA prompts for 10 days
measure: Daily withdrawal symptoms
timeFrame: Measured with daily EMA prompts for 10 days
measure: Fluctuations in pain ratings vs smoking urge
timeFrame: Measured 5 times per day with random EMA prompts for 10 days
measure: Fluctuations in pain ratings vs number of cigarettes smoked
timeFrame: Measured 5 times per day with random EMA prompts for 10 days
Secondary outcomes:
Other outcomes:
Locations:
Study officials:
affiliation: Duke University
name: Maggie Sweitzer, Ph.D.
role: PRINCIPAL_INVESTIGATOR
References: