# Using Very Low Nicotine Content Cigarettes as a Strategy to Disrupt the Pain-Smoking Reinforcement Cycle

> **NIH NIH R21** · DUKE UNIVERSITY · 2022 · $201,250

## Abstract

Tobacco smoking and chronic pain are highly comorbid conditions. Smoking and pain have
been proposed to influence each other through a reciprocal positive feedback loop, in which
pain increases motivation to smoke and smoking worsens pain over time. Nicotine has been
shown to provide mild, short-term anti-nociceptive effects, which may contribute to powerful
negative reinforcement learning. Conversely, smoking withdrawal exacerbates pain, presenting
a potential barrier to smoking cessation. The goal of the proposed research is to examine
whether switching to Very Low Nicotine Content (VLNC) cigarettes can directly weaken the
pain-smoking reinforcement cycle, and attenuate withdrawal-induced hyperalgesia, among
smokers with chronic pain. The research will employ a randomized between-subjects design to
evaluate the effects of smoking VLNC’s versus Normal Nicotine Content (NNC) cigarettes on
smoking behavior, pain, withdrawal symptoms and motivation to quit among daily smokers with
chronic (>3 months) non-cancer back pain. Moreover, ecological momentary assessments
(EMA) will be used to examine changes in bidirectional associations between pain, smoking
urge and behavior as a function of cigarette condition. Participants will complete 1-week of
baseline EMA while smoking their usual brand of cigarettes to familiarize them with study
procedures; they will then be randomized to 4-weeks of NNCs or VLNCs. EMA will continue
during weeks 1 and 4 of study cigarette use, and will assess smoking behavior and urge,
negative affect, and pain intensity and interference. Participants will attend weekly in-person
visits to obtain biomarker verification of cigarette compliance, and will complete measures of
nicotine dependence, self-efficacy and motivation to quit, and pain-related coping. At the start of
the study and at the end of 4-weeks of study cigarette use, a 24-hr smoking abstinence test will
be used to assess withdrawal symptoms and withdrawal-induced hyperalgesia. In general, we
hypothesize that switching to VLNCs will attenuate the bidirectional associations between
smoking and pain as assessed via EMA, and will lead to decreased symptoms of withdrawal
and pain during the 24-hour abstinence test. We also hypothesize that VLNCs will be
associated with improvements in abstinence self-efficacy and intention to quit smoking, and
decreased reliance on smoking to cope with pain. These results will provide critical insights into
the role of nicotine in maintaining smoking/pain associations and the potential for VLNCs to
extinguish learned associations to promote smoking cessation in this vulnerable population.

## Key facts

- **NIH application ID:** 10458026
- **Project number:** 5R21DA052729-02
- **Recipient organization:** DUKE UNIVERSITY
- **Principal Investigator:** Maggie M Sweitzer
- **Activity code:** R21 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2022
- **Award amount:** $201,250
- **Award type:** 5
- **Project period:** 2021-08-01 → 2024-07-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10458026

## Citation

> US National Institutes of Health, RePORTER application 10458026, Using Very Low Nicotine Content Cigarettes as a Strategy to Disrupt the Pain-Smoking Reinforcement Cycle (5R21DA052729-02). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/10458026. Licensed CC0.

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