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Smoking and Chronic Pain

From WikiMSK

Written by: Dr Jeremy Steinberg; peer reviewer: Dr Lucy Holtzhausen – created: 4 December 2022; last modified: 12 November 2024


The prevalence of smoking in those with chronic pain is up to double that of the general population. In the short term smoking is an analgesic, however in the long-term it is deleterious for pain as it exacerbates nociceptive, neuropathic, and psychosocial pain.[1] Smokers have higher pain intensities, number of painful areas, levels of disability, and opioid use to nonsmokers.[2] There is a positive correlation even when controlling for confounding demographic, socioeconomic, and mood disorder factors.[3] Many smokers identify coping with pain and anxiety as reasons for smoking.[4][5] There is therefore a bidirectional relationship with smoking and pain. Pain increases the desire to smoke, and smoking increases pain.[3]

Pathophysiology

The acute and chronic effects of cigarette smoking.[1]

Tobacco smoke contains nicotine and over 4000 other compounds. Nicotine plays a role in pain-related pathophysiology.

Nicotine binds to nicotinic acetylcholine receptors (nAChRs) which are found throughout the central and peripheral nervous systems and are involved in the physiology of arousal, sleep, anxiety, cognition, and pain. Nicotine also binds to opioid receptors.

Short Term Use

Cigarette smoking results in increased brain concentrations of nicotine within 7-10 seconds. It binds to nAChRs in the midbrain as well as in the peripheral nervous system. nAChR activation results in the release of noradrenaline, endogenous opioids, dopamine, and other neurotransmitters. This results in the feelings of euphoria and analgesia. The analgesic effect is from activation of the descending pain modulatory pathways and inhibition of afferent input to the dorsal horn.[1]

A meta-analysis for intranasal or transdermal nicotine found a small beneficial analgesic effect when used in the short-term for post-operative pain.[6]

Long Term Use

However inhaled nicotine has a half-life of approximately 30 minutes. This leads to a rapid decrease in the levels of the above neurotransmitters. This then leads to increased withdrawal, greater pain intensity, and cravings. Increased pain sensitivity occurs because long term use of nicotine results in neuroplastic changes with nAChR desensitisation and upregulation. The only way to overcome this would be to smoke constantly, which is not typically possible, and it would have other deleterious effects. It also results in decreased GABA levels.

Therefore with use in the longer term pain is worsened, and the short term analgesic effects are outweighed by increased pain sensitivity from nicotine withdrawal due to rapid brain elimination of nicotine. There may also be reduced endogenous opioid release, blunting of the hypothalamic-pituitary-adrenal axis during stress, and altered connectivity of the basal ganglia.

Furthermore smoking has other deleterious effects on the musculoskeletal system. It increases the risk of disc degeneration, fractures, delayed tissue healing, and osteoporosis. From a psychosocial perspective it can further intensify depressive and anxiety symptoms and cause sleep disturbance. Smokers are also more likely to abuse alcohol, other substances, and have suicidal ideation.

In rat models nicotine exposure results in improved pain thresholds after 1 to 3 weeks of exposure. However after 6 weeks of use pain thresholds are worsened. Chronic exposure leads to decreased pain thresholds in a neuropathic pain model following withdrawal.

Epidemiology

Current and previous smoking is an independent predictive factor of the prevalence and intensity of chronic pain - including nociceptive and neuropathic pain. Current smokers have greater rates of chronic pain than ex-smokers, which in turn have greater rates of pain than those that have never smoked. The prevalence of current smoking in patients with pain ranges from 42% to 68%.[1]

Chronic pain is also more severe in smokers than nonsmokers and ex-smokers when looking at pain frequency, intensity, duration, and number of painful sites.[7]

Not only is opioid use more common in smokers compared to non-smokers, there is also an increased quantity of opioid use per individual. Smoking adults with chronic pain have a 46% higher risk of starting opioids than non-smokers with chronic pain, and a 6.6 times risk of continuing opioids the next year. In comparing smokers vs non-smokers who use opioids for pain, smokers have a 95% increased risk of using a dosage of above 50 MME.[8] Even with higher use of opioids pain control is still worse than non-smokers. This association holds when controlling for confounding factors. It is also more difficult for smokers who use opioids to quite smoking. The analgesic effect of opioids is enhanced by supraspinal nicotinic acetylcholine receptors.[2]

Effect on Interventions

In the surgical setting, smokers have a higher incidence of inadequate post-operative pain control than nonsmokers and higher rates of chronic post-surgical pain regardless of the type of surgery (including arthroplasty and spinal surgery), as well as higher risk of chronic opioid use post surgery. Smokers also have poorer outcomes with nerve blocks and spinal cord simulators.[1]

Smokers may have poorer outcomes in MDT pain management programmes as well as lower rates of return to work.[1] Smokers may benefit from a high-intensity programme, with one study of a 15 day 8-hour a day programme finding that smokers had similar or better outcomes than non-smokers.[9]

Smoking Cessation

Smoking cessation is of vital importance in those with chronic pain but few smokers with pain are successfully able to quit and are often refractory to smoking cessation treatment. After initial withdrawal of nicotine, even after a few hours, there is rapid recovery of excess nAChRs from desensitisation which results in hyperexcitability of the nicotinine cholinergic system. This results in agitation driving the craving for nicotine to desensitise the nAChRs.[3]

This is why in the short term nicotine withdrawal worsens pain, however in the long term cessation appears to be beneficial.[1] Patience may be needed to see the benefits of smoking cessation on pain. and some of the harmful effects may not be reversible. Regardless of whether smoking cessation improves pain from the index pain problem, continuing to smoke may worsen pain and outcomes in the long-term.

Pain intensity may start to decrease after about 3 weeks of abstinence. However in the surgical literature, postoperative pain is worse than nonsmokers even if abstinence occurs 3 weeks before surgery.[1] One randomised trial of veteran smokers with chronic illness found no difference in pain at 5 months in those who quit versus those who continued to smoke.[10] But several other studies have found that patients who quit smoking have improvements in pain and improved response to various treatments. It is probably imperative to address underlying psychological issues.[1] In a study of over 5000 patients with pain related to various spinal disorders, those who had quit smoking during the course of treatment had significantly better pain levels than those who continued to smoke.[11] In another study of over 6000 older adults, smoking cessation over a period of four years was associated with lower rates of back pain.[12] Another study showed opioid use decreased by20% one year after smoking cessation.[8]

Prescription options to assist with smoking cessation include nicotine replacement therapy, bupropion, nortriptyline, and varenicline. As of December 2022 varenicline has been unavailable in New Zealand for many months. Bupropion and nortriptyline can be good options due to their mild analgesic effects.[1][13] It isn't clear whether nicotine replacement therapy such as patches, gum, and lozenges are beneficial in this population.

Vaping is not a good alternative because it also negatively impacts pain perception due to containing which increases pain sensitivity.[1]

Exercise should be promoted as a healthier alternative to analgesia through exercise induced hypoalgesia.[1]

Specific Conditions

Smoking is harmful in a variety of pain conditions including but not limited to headache disorders, low back pain, fibromyalgia, inflammatory arthritis, neuropathic pain, and cancer. It likely contributes to the development of these conditions.[3]

Degenerative Spinal Disease

Smoking is a strong risk factor for the development of degenerative spinal disease such.[14][15] The prevalence of smoking those with chronic low back pain is reported to be between 16-40%.[2] One large cohort study of over 70 thousand Canadians found a clear relationship between smoking and chronic low back pain risk. The prevalence was 23.3% in daily smokers compared to 15.7% in non-smokers. The association was stronger amongst younger individuals and the effect was dose dependent.[16] The rates of low back pain are higher even in passive smokers.[1]

Fibromyalgia

The rate of smoking amongst patients with fibromyalgia is higher than the general population. For example one study of 1566 patients reported a smoking prevalence of 38.7% in those with fibromyalgia compared to 24.7% of patients without fibromyalgia.[17]

Rheumatoid Arthritis

Rheumatoid arthritis is approximately twice as more prevalent in smokers compared to nonsmokers, and four times more prevalent for rheumatoid-factor positive rheumatoid arthritis.[18]

Neuropathic Pain

The rates of sciatica and postherpetic neuralgia are approximately twice that of nonsmokers.[1]

Cancer

Smoking is harmful in those with cancer for several reasons. It causes increased pain sensitivity, increased need for opioids, increased rates of chemotherapy induced peripheral neuropathy, and [1]increased pain with radiation.

Resources

Smoking cesssation in patients with pain - Iida 2022.pdf

References

Papers of particular interest have been highlighted as: ◆ of special interest ◆◆ of outstanding interest

  1. ↑ 1.00 1.01 1.02 1.03 1.04 1.05 1.06 1.07 1.08 1.09 1.10 1.11 1.12 1.13 1.14 Iida, Hiroki; Yamaguchi, Shigeki; Goyagi, Toru; Sugiyama, Yoko; Taniguchi, Chie; Matsubara, Takako; Yamada, Naoto; Yonekura, Hiroshi; Iida, Mami (2022-12). "Consensus statement on smoking cessation in patients with pain". Journal of Anesthesia. 36 (6): 671–687. doi:10.1007/s00540-022-03097-w. ISSN 1438-8359. PMC 9666296. PMID 36069935. Check date values in: |date= (help)
  2. ↑ 2.0 2.1 2.2 Orhurhu, Vwaire J.; Pittelkow, Thomas P.; Hooten, W. Michael (2015). "Prevalence of smoking in adults with chronic pain". Tobacco Induced Diseases. 13 (1): 17. doi:10.1186/s12971-015-0042-y. ISSN 2070-7266. PMC 4504349. PMID 26185492.
  3. ↑ 3.0 3.1 3.2 3.3 Khan, James S.; Hah, Jennifer M.; Mackey, Sean C. (2019-10). "Effects of smoking on patients with chronic pain: a propensity-weighted analysis on the Collaborative Health Outcomes Information Registry". Pain. 160 (10): 2374–2379. doi:10.1097/j.pain.0000000000001631. ISSN 1872-6623. PMC 6768701. PMID 31149975. Check date values in: |date= (help)
  4. ↑ Lee, Megan; Snow, Jennifer; Quon, Caroline; Selander, Kim; DeRycke, Eric; Lawless, Mark; Driscoll, Mary; Ditre, Joseph W.; Mattocks, Kristin M.; Becker, William C.; Bastian, Lori A. (2021-10). "I smoke to cope with pain: patients' perspectives on the link between cigarette smoking and pain". Wiener Klinische Wochenschrift. 133 (19–20): 1012–1019. doi:10.1007/s00508-021-01931-x. ISSN 1613-7671. PMID 34460005. Check date values in: |date= (help)
  5. ↑ Patterson, Alexander L.; Gritzner, Susan; Resnick, Michael P.; Dobscha, Steven K.; Turk, Dennis C.; Morasco, Benjamin J. (2012-03). "Smoking cigarettes as a coping strategy for chronic pain is associated with greater pain intensity and poorer pain-related function". The Journal of Pain. 13 (3): 285–292. doi:10.1016/j.jpain.2011.11.008. ISSN 1528-8447. PMC 3293999. PMID 22325299. Check date values in: |date= (help)
  6. ↑ Matthews, Annette M.; Fu, Rongwei; Dana, Tracy; Chou, Roger (2016-01-12). "Intranasal or transdermal nicotine for the treatment of postoperative pain". The Cochrane Database of Systematic Reviews. 2016 (1): CD009634. doi:10.1002/14651858.CD009634.pub2. ISSN 1469-493X. PMC 8729826. PMID 26756459.
  7. ↑ Ditre, Joseph W.; Brandon, Thomas H.; Zale, Emily L.; Meagher, Mary M. (2011-11). "Pain, nicotine, and smoking: research findings and mechanistic considerations". Psychological Bulletin. 137 (6): 1065–1093. doi:10.1037/a0025544. ISSN 1939-1455. PMC 3202023. PMID 21967450. Check date values in: |date= (help)
  8. ↑ 8.0 8.1 Encinosa, William; Bernard, Didem; Valdez, R. Burciaga (2025-01). "The association between smoking, chronic pain, and prescription opioid use: 2013-2021". The Journal of Pain (in English). 26: 104707. doi:10.1016/j.jpain.2024.104707. Check date values in: |date= (help)
  9. ↑ Hooten, W. Michael; Townsend, Cynthia O.; Bruce, Barbara K.; Schmidt, John E.; Kerkvliet, Jennifer L.; Patten, Christi A.; Warner, David O. (2009-03). "Effects of smoking status on immediate treatment outcomes of multidisciplinary pain rehabilitation". Pain Medicine (Malden, Mass.). 10 (2): 347–355. doi:10.1111/j.1526-4637.2008.00494.x. ISSN 1526-4637. PMID 18721171. Check date values in: |date= (help)
  10. ↑ Bastian, Lori A.; Fish, Laura J.; Gierisch, Jennifer M.; Stechuchak, Karen M.; Grambow, Steven C.; Keefe, Francis J. (2015-12). "Impact of Smoking Cessation on Subsequent Pain Intensity Among Chronically Ill Veterans Enrolled in a Smoking Cessation Trial". Journal of Pain and Symptom Management. 50 (6): 822–829. doi:10.1016/j.jpainsymman.2015.06.012. ISSN 1873-6513. PMID 26210348. Check date values in: |date= (help)
  11. ↑ Behrend, Caleb; Prasarn, Mark; Coyne, Ellen; Horodyski, MaryBeth; Wright, John; Rechtine, Glenn R. (2012-12-05). "Smoking Cessation Related to Improved Patient-Reported Pain Scores Following Spinal Care". Journal of Bone and Joint Surgery (in English). 94 (23): 2161–2166. doi:10.2106/JBJS.K.01598. ISSN 0021-9355.
  12. ↑ Ikeda, Takaaki; Cooray, Upul; Murakami, Masayasu; Osaka, Ken (2023-09). "Assessing the impacts of smoking cessation and resumption on back pain risk in later life". European Journal of Pain (in English). 27 (8): 973–980. doi:10.1002/ejp.2139. ISSN 1090-3801. Check date values in: |date= (help)
  13. ↑ Semenchuk, M. R.; Sherman, S.; Davis, B. (2001-11-13). "Double-blind, randomized trial of bupropion SR for the treatment of neuropathic pain". Neurology. 57 (9): 1583–1588. doi:10.1212/wnl.57.9.1583. ISSN 0028-3878. PMID 11706096.
  14. ↑ Khurana, Vini G. (2021). "Adverse impact of smoking on the spine and spinal surgery". Surgical Neurology International. 12: 118. doi:10.25259/SNI_6_2021. ISSN 2229-5097. PMC 8053459. PMID 33880223.
  15. ↑ ◆ Rajesh, Niharika; Moudgil-Joshi, Jigishaa; Kaliaperumal, Chandrasekaran (2022-01-01). "Smoking and degenerative spinal disease: A systematic review". Brain and Spine (in English). 2: 100916. doi:10.1016/j.bas.2022.100916. ISSN 2772-5294. PMC 9560562. PMID 36248118.CS1 maint: PMC format (link)
  16. ↑ Alkherayf, Fahad; Agbi, Charles (2009-10-01). "Cigarette smoking and chronic low back pain in the adult population". Clinical and Investigative Medicine. Medecine Clinique Et Experimentale. 32 (5): E360–367. doi:10.25011/cim.v32i5.6924. ISSN 1488-2353. PMID 19796577.
  17. ↑ Goesling, Jenna; Brummett, Chad M.; Meraj, Taha S.; Moser, Stephanie E.; Hassett, Afton L.; Ditre, Joseph W. (2015-07). "Associations Between Pain, Current Tobacco Smoking, Depression, and Fibromyalgia Status Among Treatment-Seeking Chronic Pain Patients". Pain Medicine (Malden, Mass.). 16 (7): 1433–1442. doi:10.1111/pme.12747. ISSN 1526-4637. PMC 4765172. PMID 25801019. Check date values in: |date= (help)
  18. ↑ Sugiyama, D.; Nishimura, K.; Tamaki, K.; Tsuji, G.; Nakazawa, T.; Morinobu, A.; Kumagai, S. (2010-01). "Impact of smoking as a risk factor for developing rheumatoid arthritis: a meta-analysis of observational studies". Annals of the Rheumatic Diseases. 69 (1): 70–81. doi:10.1136/ard.2008.096487. ISSN 1468-2060. PMID 19174392. Check date values in: |date= (help)

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