A NEW study reveals that nicotine withdrawal heightens pain sensitivity in smokers, who require substantially more postoperative analgesics than nonsmokers. Researchers identified distinct brain changes linked to hyperalgesia, helping to explain why pain responses escalate during abstinence.
Neural Mechanisms Driving Pain During Nicotine Withdrawal
Clinicians have long observed that smokers preparing for surgery often report increased discomfort, but the role of nicotine withdrawal in shaping pain has been less clear. In this study, investigators examined how nicotine withdrawal affects neural processing, behavioural pain responses, and postoperative analgesic requirements. They focused on smokers undergoing a defined abstinence window, during which pain sensitivity appears to rise before normalising after approximately three months.
Brain Function, Pain Thresholds, and Analgesic Use
Sixty male patients were enrolled, including 30 abstinent smokers and 30 nonsmokers scheduled for partial hepatectomy. Using clinical assessments, smoking histories, pain measures, and resting-state functional MRI, the researchers compared the groups. Abstinent smokers demonstrated lower pain thresholds and higher postoperative analgesic requirements. Neuroimaging revealed reduced fractional amplitude of low-frequency fluctuations in the ventromedial prefrontal cortex, increased regional homogeneity in the left middle occipital gyrus, and decreased functional connectivity between the ventromedial prefrontal cortex and both the bilateral middle temporal gyrus and precuneus. Preoperative pain threshold positively correlated with abstinence duration and specific patterns of regional brain activity and connectivity. The relationship between abstinent time and pain threshold was mediated by activity in the calcarine and posterior cingulate cortex. Moreover, dysfunction in the ventromedial prefrontal cortex and left anterior cingulate cortex fully mediated the link between withdrawal symptoms and postoperative analgesic requirements. These findings indicate that nicotine withdrawal disrupts supraspinal neural circuits in ways that contribute directly to hyperalgesia.
Implications for Clinical Practice and Pain Management
The results suggest that clinicians should consider nicotine withdrawal as a significant driver of perioperative pain and analgesic needs. Revised preoperative guidance could help reduce reliance on opioids by identifying high-risk patients and implementing targeted interventions that address withdrawal-related sensitivity. Future research may inform personalised analgesic plans and explore neuromodulatory therapies that mitigate the neural disruptions associated with nicotine withdrawal.
Reference
Wei K et al. Altered regional brain activity underlying the higher postoperative analgesic requirements in abstinent smokers: a prospective cohort study. J Neurosci. 2025;DOI:10.1523/JNEUROSCI.0109-25.2025.
