Smoking increases risk of pain chronification through shared corticostriatal circuitry

Abstract

Smoking is associated with increased incidence of chronic pain. However, the evidence is cross-sectional in nature, and underlying mechanisms remain unclear. In a longitudinal observational study, we examined the relationship between smoking, transition to chronic pain, and brain physiology. In 160 subjects with subacute back pain (SBP: back pain lasting 4–12 weeks, and no prior back pain [BP] for at least 1 year) pain characteristics, smoking status, and brain functional properties were measured repeatedly over 1 year. Sixty-eight completed the study, subdivided into recovering (SBPr, n = 31) and persisting (SBPp, n = 37), based on >20% decrease in BP over the year. Thirty-two chronic back pain (CBP: duration > 5 years) and 35 healthy controls were similarly monitored. Smoking prevalence was higher in SBP and CBP but not related to intensity of BP. In SBP, smoking status at baseline was predictive of persistence of BP 1 year from symptom onset (differentiating SBPp and SBPr with 0.62 accuracy). Smoking status combined with affective properties of pain and medication use improved prediction accuracy (0.82). Mediation analysis indicated the prediction of BP persistence by smoking was largely due to synchrony of fMRI activity between two brain areas (nucleus accumbens and medial prefrontal cortex, NAc-mPFC). In SBP or CBP who ceased smoking strength of NAc-mPFC decreased from precessation to postcessation of smoking. We conclude that smoking increases risk of transitioning to CBP, an effect mediated by corticostriatal circuitry involved in addictive behavior and motivated learning.

Lifestyle and Chronic Pain across the Lifespan: An Inconvenient Truth?

“…Changing smoking behavior in people having chronic pain can be challenging, considering the established acute analgesic effects (small to medium effect sizes) of nicotine and tobacco in humans, making smoking more rewarding and harder to give up . This notion is in line with observations of the role of the corticostriatal circuitry—involved in addictive behavior and motivated learning in people with chronic low back pain . The analgesic effect of smoking may explain why pain represents a barrier to smoking cessation, even though the analgesic effect is most likely not affecting daily pain severity in a positive way: daily smokers and those who quit smoking have higher pain severity than non‐smoking people with chronic pain .…”

What Risk Factors Are Associated With Musculoskeletal Injury in US Army Rangers? A Prospective Prognostic Study

“…Smoking is related to poorer functional outcomes, independent of the nature or severity of injury [22]. It is an independent risk factor across a variety of populations and conditions [5,26,30,42], but specifically associated with delayed healing and recurrence of pain in shoulder [6], back [29], neck [14], and multiple other exercise-related injuries [2]. It has deleterious effects on peak bone mass [8], bone mineral density [43], bone healing [28], and wound healing [4,25] as well as many other general complications [41].…”

Alcohol and Pain: A Translational Review of Preclinical and Clinical Findings to Inform Future Treatment Strategies

“…Numerous neurotransmitter systems have been implicated with shared genetic underpinnings likely influencing neural adaptations in both AUD and chronic pain. Yet, to our knowledge, no studies have examined the neural circuitry of chronic pain and AUD in human clinical samples and we could only identify 2 studies that examined neural correlates of substance use among chronic pain patients (Boissoneault et al, ; Petre et al, ). For discussion of the overlapping neural adaptations and circuitry, we recommend prior reviews on the topic (Apkarian et al, ; Egli et al, ; Elman and Borsook, ; Yeung et al, ).…”

“…To test reward system involvement in the transition from acute pain to chronic pain (i.e., pain chronification) among smokers versus nonsmokers, Petre and colleagues () conducted secondary data analyses from a longitudinal neuroimaging study of 68 individuals with subacute chronic back pain (duration of 4 to 12 weeks) who were followed for 1 year. Smoking was significantly associated with the persistence of back pain at 1 year, and this effect was mediated by functional connectivity between the nucleus accumbens (NAc) and medial prefrontal cortex (mPFC) during a pain rating task.…”