View source for Smoking and Chronic Pain

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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.<ref name=":1">{{Cite journal|last=Iida|first=Hiroki|last2=Yamaguchi|first2=Shigeki|last3=Goyagi|first3=Toru|last4=Sugiyama|first4=Yoko|last5=Taniguchi|first5=Chie|last6=Matsubara|first6=Takako|last7=Yamada|first7=Naoto|last8=Yonekura|first8=Hiroshi|last9=Iida|first9=Mami|date=2022-12|title=Consensus statement on smoking cessation in patients with pain|url=https://pubmed.ncbi.nlm.nih.gov/36069935|journal=Journal of Anesthesia|volume=36|issue=6|pages=671–687|doi=10.1007/s00540-022-03097-w|issn=1438-8359|pmc=9666296|pmid=36069935}}</ref> Smokers have higher pain intensities, number of painful areas, levels of disability, and [[Opioid Deprescribing|opioid]] use to nonsmokers.<ref name=":0">{{Cite journal|last=Orhurhu|first=Vwaire J.|last2=Pittelkow|first2=Thomas P.|last3=Hooten|first3=W. Michael|date=2015|title=Prevalence of smoking in adults with chronic pain|url=https://pubmed.ncbi.nlm.nih.gov/26185492|journal=Tobacco Induced Diseases|volume=13|issue=1|pages=17|doi=10.1186/s12971-015-0042-y|issn=2070-7266|pmc=4504349|pmid=26185492}}</ref> There is a positive correlation even when controlling for confounding demographic, socioeconomic, and mood disorder factors.<ref name=":2">{{Cite journal|last=Khan|first=James S.|last2=Hah|first2=Jennifer M.|last3=Mackey|first3=Sean C.|date=2019-10|title=Effects of smoking on patients with chronic pain: a propensity-weighted analysis on the Collaborative Health Outcomes Information Registry|url=https://pubmed.ncbi.nlm.nih.gov/31149975|journal=Pain|volume=160|issue=10|pages=2374–2379|doi=10.1097/j.pain.0000000000001631|issn=1872-6623|pmc=6768701|pmid=31149975}}</ref> Many smokers identify coping with pain and anxiety as reasons for smoking.<ref>{{Cite journal|last=Lee|first=Megan|last2=Snow|first2=Jennifer|last3=Quon|first3=Caroline|last4=Selander|first4=Kim|last5=DeRycke|first5=Eric|last6=Lawless|first6=Mark|last7=Driscoll|first7=Mary|last8=Ditre|first8=Joseph W.|last9=Mattocks|first9=Kristin M.|last10=Becker|first10=William C.|last11=Bastian|first11=Lori A.|date=2021-10|title=I smoke to cope with pain: patients' perspectives on the link between cigarette smoking and pain|url=https://pubmed.ncbi.nlm.nih.gov/34460005|journal=Wiener Klinische Wochenschrift|volume=133|issue=19-20|pages=1012–1019|doi=10.1007/s00508-021-01931-x|issn=1613-7671|pmid=34460005}}</ref><ref>{{Cite journal|last=Patterson|first=Alexander L.|last2=Gritzner|first2=Susan|last3=Resnick|first3=Michael P.|last4=Dobscha|first4=Steven K.|last5=Turk|first5=Dennis C.|last6=Morasco|first6=Benjamin J.|date=2012-03|title=Smoking cigarettes as a coping strategy for chronic pain is associated with greater pain intensity and poorer pain-related function|url=https://pubmed.ncbi.nlm.nih.gov/22325299|journal=The Journal of Pain|volume=13|issue=3|pages=285–292|doi=10.1016/j.jpain.2011.11.008|issn=1528-8447|pmc=3293999|pmid=22325299}}</ref> There is therefore a bidirectional relationship with smoking and pain. Pain increases the desire to smoke, and smoking increases pain.<ref name=":2" />
== Pathophysiology ==
[[File:Smoking pathophysiology pain.jpg|thumb|The acute and chronic effects of cigarette smoking.<ref name=":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.<ref name=":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.<ref>{{Cite journal|last=Matthews|first=Annette M.|last2=Fu|first2=Rongwei|last3=Dana|first3=Tracy|last4=Chou|first4=Roger|date=2016-01-12|title=Intranasal or transdermal nicotine for the treatment of postoperative pain|url=https://pubmed.ncbi.nlm.nih.gov/26756459|journal=The Cochrane Database of Systematic Reviews|volume=2016|issue=1|pages=CD009634|doi=10.1002/14651858.CD009634.pub2|issn=1469-493X|pmc=8729826|pmid=26756459}}</ref>

=== 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.

== Effect on Pain 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.<ref name=":1" />

Smokers may have poorer outcomes in MDT pain management programmes as well as lower rates of return to work.<ref name=":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.<ref>{{Cite journal|last=Hooten|first=W. Michael|last2=Townsend|first2=Cynthia O.|last3=Bruce|first3=Barbara K.|last4=Schmidt|first4=John E.|last5=Kerkvliet|first5=Jennifer L.|last6=Patten|first6=Christi A.|last7=Warner|first7=David O.|date=2009-03|title=Effects of smoking status on immediate treatment outcomes of multidisciplinary pain rehabilitation|url=https://pubmed.ncbi.nlm.nih.gov/18721171|journal=Pain Medicine (Malden, Mass.)|volume=10|issue=2|pages=347–355|doi=10.1111/j.1526-4637.2008.00494.x|issn=1526-4637|pmid=18721171}}</ref>

== Smoking Cessation ==
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.<ref name=":2" />

This is why In the short term nicotine withdrawal worsens pain, however in the long term cessation may be beneficial.<ref name=":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, continuing to smoke may worsen pain and outcomes in the long-term.

The prevalence rates of chronic pain in ex-smokers is higher than nonsmokers. However chronic pain is more severe in smokers than nonsmokers and ex-smokers when looking at pain frequency, intensity, duration, and number of painful sites.<ref>{{Cite journal|last=Ditre|first=Joseph W.|last2=Brandon|first2=Thomas H.|last3=Zale|first3=Emily L.|last4=Meagher|first4=Mary M.|date=2011-11|title=Pain, nicotine, and smoking: research findings and mechanistic considerations|url=https://pubmed.ncbi.nlm.nih.gov/21967450|journal=Psychological Bulletin|volume=137|issue=6|pages=1065–1093|doi=10.1037/a0025544|issn=1939-1455|pmc=3202023|pmid=21967450}}</ref>  

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.<ref name=":1" /> However 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.<ref>{{Cite journal|last=Bastian|first=Lori A.|last2=Fish|first2=Laura J.|last3=Gierisch|first3=Jennifer M.|last4=Stechuchak|first4=Karen M.|last5=Grambow|first5=Steven C.|last6=Keefe|first6=Francis J.|date=2015-12|title=Impact of Smoking Cessation on Subsequent Pain Intensity Among Chronically Ill Veterans Enrolled in a Smoking Cessation Trial|url=https://pubmed.ncbi.nlm.nih.gov/26210348|journal=Journal of Pain and Symptom Management|volume=50|issue=6|pages=822–829|doi=10.1016/j.jpainsymman.2015.06.012|issn=1873-6513|pmid=26210348}}</ref> 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.<ref name=":1" />

Vaping is not a good alternative because it also negatively impacts pain perception due to containing which increases pain sensitivity.<ref name=":1" />

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.<ref name=":1" /><ref>{{Cite journal|last=Semenchuk|first=M. R.|last2=Sherman|first2=S.|last3=Davis|first3=B.|date=2001-11-13|title=Double-blind, randomized trial of bupropion SR for the treatment of neuropathic pain|url=https://pubmed.ncbi.nlm.nih.gov/11706096|journal=Neurology|volume=57|issue=9|pages=1583–1588|doi=10.1212/wnl.57.9.1583|issn=0028-3878|pmid=11706096}}</ref>

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

== Opioid Use ==
Not only is opioid use more common in smokers compared to non-smokers, there is also an increased quantity of opioid use per individual. 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.<ref name=":0" />

== 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.<ref name=":2" />

=== Degenerative Spinal Disease ===
Smoking is a strong risk factor for the development of degenerative spinal disease such.<ref>{{Cite journal|last=Khurana|first=Vini G.|date=2021|title=Adverse impact of smoking on the spine and spinal surgery|url=https://pubmed.ncbi.nlm.nih.gov/33880223|journal=Surgical Neurology International|volume=12|pages=118|doi=10.25259/SNI_6_2021|issn=2229-5097|pmc=8053459|pmid=33880223}}</ref><ref>{{Special|1}}{{Cite journal|last=Rajesh|first=Niharika|last2=Moudgil-Joshi|first2=Jigishaa|last3=Kaliaperumal|first3=Chandrasekaran|date=2022-01-01|title=Smoking and degenerative spinal disease: A systematic review|url=https://www.sciencedirect.com/science/article/pii/S2772529422000571|journal=Brain and Spine|language=en|volume=2|pages=100916|doi=10.1016/j.bas.2022.100916|issn=2772-5294|pmc=PMC9560562|pmid=36248118}}</ref> The prevalence of smoking those with [[Chronic Low Back Pain|chronic low back pain]] is reported to be between 16-40%.<ref name=":0" /> 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.<ref>{{Cite journal|last=Alkherayf|first=Fahad|last2=Agbi|first2=Charles|date=2009-10-01|title=Cigarette smoking and chronic low back pain in the adult population|url=https://pubmed.ncbi.nlm.nih.gov/19796577|journal=Clinical and Investigative Medicine. Medecine Clinique Et Experimentale|volume=32|issue=5|pages=E360–367|doi=10.25011/cim.v32i5.6924|issn=1488-2353|pmid=19796577}}</ref> The rates of low back pain are higher even in passive smokers.<ref name=":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.<ref>{{Cite journal|last=Goesling|first=Jenna|last2=Brummett|first2=Chad M.|last3=Meraj|first3=Taha S.|last4=Moser|first4=Stephanie E.|last5=Hassett|first5=Afton L.|last6=Ditre|first6=Joseph W.|date=2015-07|title=Associations Between Pain, Current Tobacco Smoking, Depression, and Fibromyalgia Status Among Treatment-Seeking Chronic Pain Patients|url=https://pubmed.ncbi.nlm.nih.gov/25801019|journal=Pain Medicine (Malden, Mass.)|volume=16|issue=7|pages=1433–1442|doi=10.1111/pme.12747|issn=1526-4637|pmc=4765172|pmid=25801019}}</ref>

=== 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.<ref>{{Cite journal|last=Sugiyama|first=D.|last2=Nishimura|first2=K.|last3=Tamaki|first3=K.|last4=Tsuji|first4=G.|last5=Nakazawa|first5=T.|last6=Morinobu|first6=A.|last7=Kumagai|first7=S.|date=2010-01|title=Impact of smoking as a risk factor for developing rheumatoid arthritis: a meta-analysis of observational studies|url=https://pubmed.ncbi.nlm.nih.gov/19174392|journal=Annals of the Rheumatic Diseases|volume=69|issue=1|pages=70–81|doi=10.1136/ard.2008.096487|issn=1468-2060|pmid=19174392}}</ref>

=== Neuropathic Pain ===
The rates of sciatica and postherpetic neuralgia are approximately twice that of nonsmokers.<ref name=":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 <ref name=":1" />increased pain with radiation.

==Resources==
{{PDF|Smoking cesssation in patients with pain - Iida 2022.pdf}}

== References ==
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[[Category:Lifestyle]]
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