Acute analgesic effects of nicotine and tobacco in humans: a meta-analysis

Abstract

Although animal models have consistently demonstrated acute pain-inhibitory effects of nicotine and tobacco, human experimental studies have yielded mixed results. The main goal of this meta-analysis was to quantify the effects of nicotine/tobacco administration on human experimental pain threshold and tolerance ratings. A search of PubMed and PsychINFO online databases identified 13 eligible articles, including k = 21 tests of pain tolerance (N = 393) and k = 15 tests of pain threshold (N = 339). Meta-analytic integration for both threshold and tolerance outcomes revealed that nicotine administered via tobacco smoke and other delivery systems (e.g., patch, nasal spray) produced acute analgesic effects that may be characterized as small to medium in magnitude (Hedges’ g = .35, 95% CI = .21-.50). Publication bias-corrected estimates remained significant and indicated that these effects may be closer to small. Gender composition was observed to be a significant moderator, such that pain threshold effects were more robust among samples that included more men than women. These results help to clarify a mixed literature, and may ultimately help to inform the treatment of both pain and nicotine dependence. Pain and tobacco smoking are both highly prevalent and comorbid conditions, current smoking has been associated with more severe chronic pain and physical impairment, and acute nicotine-induced analgesia could make smoking more rewarding and harder to give up. Future research should employ dynamic measures of experimental pain reactivity and further explore biopsychosocial mechanisms of action.

The Impact of Tobacco Cigarette Smoking on Spinal Cord Stimulation Effectiveness in Chronic Spine–Related Pain Patients

“…The acute analgesic effects of nicotine and tobacco in cigarettes have consistently been demonstrated in experimental animals, 41,42 albeit in human subjects the results have been controversial with the existence of paradoxical evidence. [3][4][5] Whereas some studies presented smoking as an adequate pain reliever in humans, 5,43,44 others found that they accentuate the sensation of pain 3,4,6,7 as well as cause functional impairment. 8,11 Findings of our study indicate that chronic spine-related pain patients who were managed with spinal cord stimulation do indeed report higher pain scores if they continue to smoke compared with both former smokers and lifelong nonsmokers, which goes in concordance with the majority of literature published about tobacco smoking and chronic pain.…”

“…2 One common association to chronic pain is tobacco smoking. Despite the observation that smoking may provide analgesic effects, [3][4][5] however, smokers have previously reported higher pain scores 6,7 and more associated functional impairments than lifelong nonsmokers. [8][9][10][11] According to the US Centers for Disease Control and Prevention, smoking remains the single most preventable cause of death in the United States.…”

Anxiety and Depression in Bidirectional Relations Between Pain and Smoking

“…Data derived from ecological momentary assessment and experimental research paradigms further indicate that the experience of pain can increase urge to smoke and function as a proximal antecedent of smoking behavior (Dhingra et al, 2014; Ditre & Brandon, 2008), especially when individuals hold expectations for nicotine/tobacco-related pain reduction (Ditre, Heckman, Butts, & Brandon, 2010). Indeed, new meta-analytic findings show that nicotine delivered via tobacco smoke and other means (e.g., nicotine patch) can produce acute analgesic effects that may be characterized as small to moderate in magnitude (Ditre, Heckman, Zale, Kosiba, & Maisto, under review). Finally, consistent with evidence that pain can motivate smoking, there are some data to suggest that pain may impede smoking cessation.…”

“…For example, researchers have suggested that high dose nicotine replacement therapy might confer acute analgesic benefits that help to mitigate pain during the early stages of quitting (Ditre, Heckman, et al, under review). In addition, bupropion is an efficacious smoking cessation aid that is also approved by the Food and Drug Administration (FDA) for treatment of depression (Fiore et al, 2008), and there is some evidence that smokers are less likely to relapse during the early stages of a quit attempt when bupropion and nicotine replacement therapy are combined (Fiore et al, 2008; Piper et al, 2007).…”

Marijuana and Prescription Pain Reliever Use among Cigarette Smokers

“…The relationship between the use of these two substances has a basis in the biological connection between them, as the endogenous opioid system is an underlying mechanism for several behavioral outcomes related to nicotine (i.e., nicotine craving, anxiolytic and anxiogenic effects, and nicotine withdrawal symptoms) (Nuechterlein et al 2016; Hadjiconstantinou & Neff 2011; Berrendero et al 2010). Like marijuana, nicotine is involved in anti-nociception via endogenous opioid system mediation, suggesting that nicotine is used for the self-medication of pain (Kishioka et al 2014; Ditre et al 2016); and in fact, nicotine heightens the anti-nociceptive effects of both opioids and marijuana (Kohut 2017). Several studies have documented common use patterns among tobacco, marijuana, and opioids/PPRs (Arterberry et al 2016; Abrahamsson & Hakansson 2015; Fiellin et al 2013).…”