Bookmark and Share

Back to Table of Contents | March 2011

Clinical and Health Affairs

Smoking and Chronic Pain: A Real-but-Puzzling Relationship

By Toby N. Weingarten, M.D., Yu Shi, M.D., M.P.H., Carlos B. Mantilla, M.D., Ph.D., W. Michael Hooten, M.D., and David O. Warner, M.D

■ Smoking produces profound changes in physiology beyond those associated with the delivery of nicotine to the bloodstream. It has long been known that these changes put patients at risk for heart disease, cancers, and lung diseases. More recently, it has been discovered that smoking is a risk factor for chronic pain. Robust epidemiological evidence is showing that smokers not only have higher rates of chronic pain but also rate their pain as more intense than nonsmokers. Because the relationship between smoking and pain is of relevance to clinicians in many specialties, researchers at Mayo Clinic are examining this relationship in depth. This article describes some of what they and others have discovered in recent years about the interactions between smoking and chronic pain.

Recent evidence suggests that smokers are more likely than nonsmokers to experience chronic pain.1-6 In fact, it appears that chronic pain is even more prevalent among former smokers than it is among those who have never smoked.6 In addition, smokers with chronic pain indicate that their pain is more intense than that of nonsmokers and say that their pain is associated with more occupational and social impairment.7-10 These observations are even more interesting given that they are contrary to what would be expected because of nicotine’s known analgesic properties. Thus, the relationship between pain and smoking is a fascinating phenomenon that has a considerable number of clinical implications. Although it is not fully understood, research is beginning to shed light on how smoking and pain interact.

The Many Interactions between Smoking and Chronic Pain
Findings from recent prospective studies suggest a causal relationship between smoking and chronic pain. For example, one study found that Finnish adolescents who smoke at age 16 were more likely to develop pain symptoms by age 18.4 Another one found that adolescent smokers were at increased risk for hospitalization for low-back pain later in life and that male smokers were at increased risk for lumbar discectomy.3 A longitudinal study of 9,600 twins found a dose-response relationship between the number of cigarettes smoked and the development of back pain.1

The Benefits of Cognitive Behavioral Therapy

Smokers respond as well as nonsmokers to cognitive behavioral therapy for the treatment of chronic pain. For example, smokers who completed an intense three-week cognitive behavioral therapy rehabilitative program for patients with severe chronic pain at Mayo Clinic’s Pain Rehabilitation Center experienced equal or better responses than nonsmokers and were as able to successfully taper off opioids, despite greater pain and functional impairment at program entry.1 Similar observations have been made in smokers with fibromyalgia and who were treated with cognitive behavioral therapy at Mayo’s Fibromyalgia and Chronic Fatigue Clinic.

1. Hooten WM, Townsend CO, Bruce BK, Warner DO. The effects of smoking status on opioid tapering among patients with chronic pain. Anesth Analg. 2009;108(1):308-15.

Smokers with chronic pain are more adversely affected by their pain than nonsmokers with chronic pain. Studies of patients presenting to the Mayo Clinic Pain Rehabilitation Center, Outpatient Pain Clinic, Orofacial Pain Clinic, and Fibromyalgia and Chronic Fatigue Clinic consistently show that smokers report greater pain intensity and greater functional impairment than nonsmokers.7-10 In addition, their scores on measures of life interference were worse. For example, smokers with fibromyalgia missed more days of work; reported worse sleep, greater anxiety, and depression; and had more pain, stiffness, and fatigue than nonsmokers with fibromyalgia.9

Because nicotine has analgesic properties and smoking a cigarette can blunt pain perception,11 the higher prevalence and increased severity of chronic pain in smokers as compared with nonsmokers may seem surprising. Researchers are exploring this apparent paradox. They have found that nicotine-habituated animals undergoing nicotine withdrawal demonstrate increased sensitivity to pain stimuli.12 They have also found that when human smokers are deprived of nicotine, they perceive pain stimuli earlier and have reduced tolerance for pain.13,14 Thus, some postulate that nicotine withdrawal could increase a smoker’s perception of pain and even the intensity of chronic pain.

Heightened awareness of pain in response to nicotine withdrawal could, in turn, further encourage smoking because it reduces a person’s perception of pain and/or helps them cope with the pain or mitigates anxiety associated with increased pain. For example, in at least one study, smokers reported that feeling pain made them want to smoke.15 Current research at Mayo Clinic is examining if and how pain motivates female smokers with fibromyalgia to smoke.

Researchers are also attempting to identify the mechanisms that might lead to increased pain in smokers. Some point to the changes that occur in the neuroendocrine system in response to long-term smoking. In the nonsmoker, the physiologic stress that results from pain activates the sympathetic nervous system and the hypothalamic-pituitary-adrenal (HPA) axis. The increased sympathetic output blunts pain perception. However, the HPA system is down-regulated in smokers, which may increase their perception of pain.

Another potential explanation may be that smoking accelerates degenerative changes such as those from osteoporosis and lumbar disc disease, and impairs bone healing. Such changes could predispose smokers to injury, impede healing, and subsequently increase their risk for future chronic pain.

Psychosocial factors also may have an effect. Current scientific understanding of biological processes and neural pathways suggests a link between depression and pain. It is known that smokers have higher rates of mood disorders such as depression and anxiety than nonsmokers and that patients with these mood disorders have more chronic pain. We also know that patients with chronic pain have higher rates of mood disorders. We recently reviewed a national data set and found that smoking increased the likelihood of pain in older adults but only in those who were also depressed.16 However, in a recent analysis of patients treated at our Pain Rehabilitation Center, we found that pain severity was independently associated with depression severity but not smoking status.17 Obviously, the interactions between smoking, depression, and chronic pain are not completely understood and are complex. However, the clinician who encounters a smoker with chronic pain should strongly consider that mood disorders also may be present.

Research is also examining how income and marital status play into this issue. Smokers tend to be less educated, poorer, and more likely to be unemployed and divorced than nonsmokers. In addition, as smoking rates decline, smokers are becoming increasingly marginalized in society. Weingarten et al. reported that 50% of smokers presenting to our outpatient tertiary pain clinic were unemployed or disabled, compared with 18% of nonsmokers.8 These differences suggest smokers are more isolated and lacking in social support than nonsmokers. It is thought that these factors could contribute to functional impairment from chronic pain.

Another consideration is that current and former heavy smokers are more likely to use prescription analgesics.18 We observed that more smokers than nonsmokers admitted to our Pain Rehabilitation Center used opioid analgesics and used them at higher doses.18 In addition, we discovered that male smokers consumed the greatest quantities of opioid analgesics.19 Smokers are known to have higher rates of drug abuse, and smoking is almost ubiquitous among opioid abusers. We also know that smoking alters the pharmacokinetics of opioids. A study comparing the effects of hydrocodone on both smokers and nonsmokers with back pain found that the smokers used more hydrocodone tablets yet continued to report greater pain. Interestingly, despite taking higher doses of hydrocodone, they had lower serum hydrocodone levels.20 An explanation for this may be that the polycyclic aromatic hydrocarbons, substances in cigarette smoke, induce P450 enzymes involved in morphine metabolism. This could account for the higher consumption of opioids in male smokers with chronic pain.

Tobacco Cessation in Chronic Pain Patients
Current guidelines recommend that clinicians advise tobacco users to quit and provide them with the assistance to do so at every encounter. Certainly chronic pain patients would benefit from stopping smoking. However, given the imperfectly understood relationship between pain and smoking, it is not clear how tobacco abstinence affects chronic pain. In the short term, nicotine abstinence has the potential to make it worse, and stopping smoking would remove a mechanism that smokers perceive as useful in coping with anxiety. Yet, in the long term, recovery from the effects of smoking might improve chronic pain.

Smokers who suffer from chronic pain have the same motivation to quit as smokers who do not have pain.21 However, we found that very few patients enrolled in our Pain Rehabilitation Center who smoked could successfully quit despite receiving tobacco-intervention services.10 We need to find ways to help smokers with chronic pain quit successfully. One approach might be to help them adopt coping strategies other than smoking such as relaxation techniques and behavior modifications. Clearly, we need additional research to better understand the effects of nicotine abstinence on chronic pain in order to develop effective interventions that can be readily applied in the clinical setting.

Chronic pain is among the many health problems associated with smoking. When smokers develop chronic pain, their symptoms and disability are often worse than those of nonsmokers with chronic pain. The reasons for these observations are likely multifactorial; but as yet they are not clear. Clinicians should provide tobacco-cessation interventions to their patients with chronic pain who use tobacco even though more research is needed regarding how smoking cessation might affect their pain and how best to help them quit. MM

Toby Weingarten is an assistant professor of anesthesiology, Yu Shi is a research fellow, Carlos Mantilla is an associate professor of anesthesiology and physiology, W. Michael Hooten is an assistant professor of anesthesiology, and David Warner is a professor of anesthesiology at Mayo Clinic.

The authors’ research is funded by the Mayo Foundation.

1. Hestbaek L, Leboeuf-Yde C, Kyvik KO. Are lifestyle-factors in adolescence predictors for adult low back pain? A cross-sectional and prospective study of young twins. BMC Musculoskelet Disord. 2006;7:27.
2. Leboeuf-Yde C. Smoking and low back pain. A systematic literature review of 41 journal articles reporting 47 epidemiologic studies. Spine. 1999;24(14): 1463-70.
3. Mattila VM, Saarni L, Parkkari J, Koivusilta L, Rimpela A. Predictors of low back pain hospitalization--a prospective follow-up of 57,408 adolescents. Pain. 2008;139(1):209-17.
4. Mikkonen P, Leino-Arjas P, Remes J, Zitting P, Taimela S, Karppinen J. Is smoking a risk factor for low back pain in adolescents? A prospective cohort study. Spine. 2008;33(5):527-32.
5. Miranda H, Viikari-Juntura E, Punnett L, Riihimaki H. Occupational loading, health behavior and sleep disturbance as predictors of low-back pain. Scand J Work Environ Health. 2008; 34(6):411-9.
6. Palmer KT, Syddall H, Cooper C, Coggon D. Smoking and musculoskeletal disorders: findings from a British national survey. Ann Rheum Dis. 2003;62(1):33-6.
7. Weingarten TN, Iverson BC, Shi Y, Schroeder DR, Warner DO, Reid KI. Impact of tobacco use on the symptoms of painful temporomandibular joint disorders. Pain. 2009;147(1-3):67-71.
8. Weingarten TN, Moeschler SM, Ptaszynski AE, Hooten WM, Beebe TJ, Warner DO. An assessment of the association between smoking status, pain intensity, and functional interference in patients with chronic pain. Pain Physician. 2008;11(5):643-53.
9. Weingarten TN, Podduturu VR, Hooten WM, Thompson JM, Luedtke CA, Oh TH. Impact of tobacco use in patients presenting to a multidisciplinary outpatient treatment program for fibromyalgia. Clin J Pain. 2009;25(1):39-43.
10. Hooten WM, Townsend CO, Bruce BK, et al. Effects of smoking status on immediate treatment outcomes of multidisciplinary pain rehabilitation. Pain Med. 2009;10(2):347-55.
11. Girdler SS, Maixner W, Naftel HA, Stewart PW, Moretz RL, Light KC. Cigarette smoking, stress-induced analgesia and pain perception in men and women. Pain. 2005;114(3):372-85.
12. Biala G, Budzynska B, Kruk M. Naloxone precipitates nicotine abstinence syndrome and attenuates nicotine-induced antinociception in mice. Pharmacol Rep. 2005;57(6):755-60.
13. Perkins KA, Grobe JE, Stiller RL, et al. Effects of nicotine on thermal pain detection in humans. Exper Clin Psychopharmacol. 1994;2(1):95-106.
14. Silverstein B. Cigarette smoking, nicotine addiction, and relaxation. J Pers Soc Psychol. 1982; 42(42):946-50.
15. Ditre JW, Brandon TH. Pain as a motivator of smoking: effects of pain induction on smoking urge and behavior. J Abnorm Psychol. 2008;117(2):467-72.
16. Shi Y, Hooten WM, Roberts RO, Warner DO. Modifiable risk factors for incidence of pain in older adults. Pain. 2010;151(2):366-71.
17. Hooten WM, Shi Y, Gazelka HM, Warner DO. The effects of depression and smoking on pain severity and opioid use in patients with chronic pain. Pain. 2011;152(1):223-9.
18. John U, Alte D, Hanke M, Meyer C, Volzke H, Schumann A. Tobacco smoking in relation to analgesic drug use in a national adult population sample. Drug Alcohol Depend. 2006;85(1):49-55.
19. Hooten WM, Townsend CO, Bruce BK, Warner DO. The effects of smoking status on opioid tapering among patients with chronic pain. Anesth Analg. 2009;108(1):308-15.
20. Ackerman WE 3rd, Ahmad M. Effect of cigarette smoking on serum hydrocodone levels in chronic pain patients. J Ark Med Soc. 2007;104(1):19-21.
21. Hahn EJ, Rayens MK, Kirsh KL, Passik SD. Brief report: pain and readiness to quit smoking cigarettes. Nicotine Tob Res. 2006;8(3):473-80.

. .