Emerging research reveals that people with substance use disorders (SUDs) may have increased pain sensitivity/hyperalgesia when withdrawing from addictive substances. Understanding how drug withdrawal affects pain is a major area of basic/clinical investigation.
A December 2025 neuroimaging study by Wei and colleagues offered detailed evidence linking short-term smoking abstinence to increased pain perception. This study enrolled 60 men preparing for surgery, assigning them to the abstinent smoker group or the nonsmoker group. Because smokers preparing for elective surgery are typically instructed to quit on hospital admission, the researchers studied individuals with a short period of cessati…
Emerging research reveals that people with substance use disorders (SUDs) may have increased pain sensitivity/hyperalgesia when withdrawing from addictive substances. Understanding how drug withdrawal affects pain is a major area of basic/clinical investigation.
A December 2025 neuroimaging study by Wei and colleagues offered detailed evidence linking short-term smoking abstinence to increased pain perception. This study enrolled 60 men preparing for surgery, assigning them to the abstinent smoker group or the nonsmoker group. Because smokers preparing for elective surgery are typically instructed to quit on hospital admission, the researchers studied individuals with a short period of cessation. The researchers demonstrated that newly abstinent smokers had significantly higher pain than nonsmokers, as well as substantially higher postoperative opioid needs for pain control. These findings confirmed earlier work from the same group showing reduced tolerance to electrical pain stimuli and greater narcotic use after surgery.
Nicotine withdrawal leads not only to increased pain perception but also to increased emotional awareness of painful stimuli. This explains why abstinent smokers report more subjective pain and need higher postoperative analgesic doses. Surgical teams often struggle with postoperative pain management, and this new evidence explains why their analgesic needs may exceed expectations. Nicotine replacement therapy (NRT) might mitigate withdrawal-hyperalgesia, and preliminary findings do show improved pain thresholds.
This hyperalgesia appears pronounced during the early weeks of abstinence and slowly normalizes over three months. The short preoperative nicotine detox and abstinence period that is commonly advised for surgical safety may paradoxically increase short-term pain sensitivity and medication requirements while still offering long-term health benefits.
Health providers, especially anesthesiologists and surgeons, ask patients to stop smoking and using drugs before surgery. But we know SUD detox can make people highly sensitive to pain with elevated pain perception and reduced pain relief from pain medications. Recommending ending smoking before major surgery is essential. Still, detox and SUD histories need to be considered when calculating anesthesia and pain medication doses, and the duration necessary; standard postoperative dosing is often inadequate.
Opioid Use Disorders and Hyperalgesia
Although the specific neuropharmacology of substances differs, opioids, alcohol, and cannabis each show similarities to nicotine and nicotine withdrawal pain sensitivity changes. In contrast, however, cocaine, methamphetamine, and benzodiazepines have limited pain sensitization effects during withdrawal.
When opioid-dependent individuals are detoxified and begin acute withdrawal, pain sensitivity rises sharply. Studies consistently show lowered heat, cold, mechanical, and electrical pain thresholds during withdrawal, as well as increased ongoing pain despite the absence of new injury. Opioid withdrawal offers the clearest, best-documented example of withdrawal-associated hyperalgesia in humans, typically more intense and longer-lasting than nicotine-related hyperalgesia.
In addition to risks associated with preoperative opioid use and abuse, pain management during the perioperative period can be challenging, as these patients tend to develop tolerance, opioid-induced hyperalgesia, and higher postoperative pain scores, ***requiring three to four times higher doses of opioids ***compared to non-tolerant individuals. As a result of increased opioid requirements, these patients also experience increased risks for perioperative complications, including excessive sedation, respiratory depression, and a longer hospital stay, as well as higher costs.
Alcohol Withdrawal and Pain
Alcohol withdrawal produces increased pain sensitivity. Controlled human studies have demonstrated greater spontaneous pain in individuals undergoing detoxification from heavy alcohol use. This phenomenon likely reflects the neuroadaptive consequences of chronic alcohol exposure which, of course, has pain-relieving effects.
Cannabis, Anesthesia, and Pain Management
It’s crucial for patients to inform their health care providers about cannabis use before surgery to ensure proper pain management and anesthesia planning, as cannabis can significantly impact outcomes. A large Cleveland Clinic study of surgical patients currently or previously using cannabis had significantly higher postoperative opioid consumption and pain scores than nonusers. Higher doses of anesthesia drugs are often required for cannabis users to stay sedated and pain-free during procedures.
Individuals using cannabis within 30 days before surgery were compared to patients who never used cannabis. The patients previously using cannabis suffered significantly more pain during the first 24 hours after surgery compared to patients who never used cannabis. Also, cannabis users consumed more opioids after surgery than those who had not used cannabis. Cannabis use disorders are increasing in the U.S., as is the need to detox from cannabis before surgery.
Studies have found that cannabis users need more potent anesthesia (like propofol) and significantly more opioids (like fentanyl) to achieve the same pain relief as non-users. Although cannabis withdrawal hyperalgesia has not been studied as extensively as opioid or nicotine hyperalgesia, evidence is accumulating.
Stimulants
In contrast, cocaine and methamphetamine withdrawal evidence is inconsistent, and the magnitude of the effect is modest compared with nicotine, opioids, alcohol, or cannabis.
Summary
When a patient with a substance use disorder (SUD) requests more analgesia than the care team anticipates, anesthesiologists approach the situation as a clinical pain-management and safety problem, not a moral or disciplinary one. They reassess location or source of pain and surgical factors, assume a physiologic explanation first, and use multimodal, individualized pain strategies. Often, when opioids are titrated to pain effect, they are at higher doses than opioid-naïve patients. Withholding opioids solely due to SUD history is generally considered substandard care.
Short-term abstinence (days to weeks) may heighten pain sensitivity. Hyperalgesia has emerged as a core withdrawal phenomenon across multiple addictive drugs. Heightened pain during abstinence not only complicates pain management, anesthesiology, and surgical care, but also reinforces drug-taking by creating negative reinforcement loops sustaining addiction and undermining cessation. This new neuroimaging study advances our understanding of nicotine withdrawal by demonstrating how hyperalgesia results from detox, sensory amplification, disrupted network regulation, and altered prefrontal function.
References
Wei K, Tao K, Bi Y, Miao X, Xiao H, Zhang Y, Qiu H, Zhu J, Chen Q, Shen L, Xu H, Ma M, Hu L, Wang K, Lu Z. Altered regional brain activity underlying the higher postoperative analgesic requirements in abstinent smokers: A prospective cohort study.. J Neurosci. 2025 Dec 8:e0109252025. doi: 10.1523/JNEUROSCI.0109-25.2025. Epub ahead of print. PMID: 41360674.
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Ekrami E, Sari S, Kopac O, Wang D, Mascha EJ, Stamper S, Esa WAS, Nair H, Ruetzler K, Turan A. Association Between Cannabis Use and Opioid Consumption, Pain, and Respiratory Complications After Surgery: A Retrospective Cohort Analysis. Anesth Analg. 2024 Oct 1;139(4):724-733. doi: 10.1213/ANE.0000000000006785. Epub 2024 Jan 8. PMID: 38190341.
Rubenstein, Dana,b,*; Green, Michael J.C; Sweitzer, Maggie M.A; Keefe, Francis J.A; McClernon, F. Josepha,B. Bidirectional relationships between pain and patterns of cannabis and tobacco use in a US nationally representative sample. PAIN 166(3):p 518- 526, March 2025. | DOI: 10.1097/j.pain.0000000000003381