Analgesic Effects of Nicotine

December 28, 2020

During perioperative anesthesia management, physicians face unique challenges when treating patients who smoke cigarettes. Besides the detrimental impact of smoking on the respiratory system and wound healing, nicotine addiction can significantly affect a patient’s recovery timeline [1]. Smokers exhibit an increased pain threshold; researchers attribute this, at least partially, to the analgesic effects of nicotine [1]. However, patients who smoke also demonstrate an augmented level of chronic pain, which may culminate in higher received doses of morphine [1]. Research on the analgesic effects of nicotine may result in alternative tools for pain management. 

Nicotine’s analgesic effects are likely caused by its activation of presynaptic nicotinic cholinergic receptors [2, 3]. These receptors cue the local release of pain inhibitors such as serotonin and norepinephrine [2]. Nicotine also has anti-inflammatory effects and may promote the release of endogenous opioids, both of which would also contribute to decreased pain [3]. Compared to opioids, nicotine has opposite side effects: nicotine intake often increases the ventilatory drive and stimulation [2]. However, it can trigger nausea in non-smokers while serving as an antiemetic for smokers, much like opioids [2].  

Although animal studies had previously suggested the efficacy of nicotine in pain management, the first human study to elucidate this correspondence occurred in 2004 [1]. The researchers administered a single 3 mg dose of intranasal nicotine to 20 healthy, non-smoking women (mean age 45, with a standard deviation of 8 years) in a randomized, double-blind, placebo-controlled trial [4]. The subjects were to undergo uterine surgery via a low transverse incision [4]. The women who received nicotine reported less pain after the first and twenty-fourth hours following surgery and used 50% less morphine than the control group [4]. Later studies by Habib et al. and Hong et al. corroborated these findings [3]. In the former experiment, 90 nonsmoking men who were to undergo retropubic prostatectomy reported significant decreases in morphine use in comparison to the control group [5]. As for the Hong et al. study, 40 non-smokers undergoing abdominal or pelvic surgery reported both lower self-reported pain scores and decreased morphine use [6]. 

Despite these promising results, not all studies have reported the same positive correspondence between nicotine use and decreased pain. In the Habib et al. study, subjects did not report a significantly lower rate of perioperative pain in comparison to the control group [3]. Another 2008 study reported neither lower pain scores nor morphine dosages in patients receiving intranasal nicotine treatment following surgery [7]. Additionally, there was no difference between groups in terms of vomiting and nausea [7]. One explanation for the disparity in these results versus those of other studies’ may be the inclusion of smokers in the trial–none of the previous trials included smokers–and the greater dose of nicotine administered to patients [3].  

Researchers must still explore safety concerns, optimal doses, and efficacy on smoking patients before forming decisive conclusions about nicotine’s analgesic benefits [3]. In particular, the addictive nature of nicotine necessitates strict caution and cost-benefit analyses. With time, alternative antinociceptive may offer physician a robust avenue for pain management. 


[1] D. O. Warner, “Tobacco dependence in surgical patients,” Current Opinion in Anaesthesiology, vol. 20, no. 3, p. 279-283, June 2007. [Online]. Available:

[2] G. Diaz and P. Flood, “Strategies for effective postoperative pain management,” Minerva Anestesiologica, vol. 72, no. 3, p. 145-150, March 2006. [Online]. Available:

[3] N. L. Benowitz, “Nicotine and Postoperative Management of Pain,” Anesthesia & Analgesia, vol. 107, no. 3, p. 739-741, September 2008. [Online]. Available:

[4] P. Flood and D. Daniel, “Intranasal Nicotine for Postoperative Pain Treatment,” Anesthesiology, vol. 101, no. 6, p. 1417-1421, December 2004. [Online]. Available:

[5] A. S. Habib et al., “Transdermal Nicotine for Analgesia After Radical Retropubic Prostatectomy,” Anesthesia & Analgesia, vol. 107, no. 3, p. 999-1004, September 2008. [Online]. Available:

[6] D. Hong et al., “Transdermal Nicotine Patch for Postoperative Pain Management: A Pilot Dose-Ranging Study,” Anesthesia & Analgesia, vol. 107, no. 3, p. 1005-1010, September 2008. [Online]. Available:

[7] A. Turan et al., “Transdermal Nicotine Patch Failed to Improve Postoperative Pain Management,” Anesthesia & Analgesia, vol. 107, no. 3, p. 1011-1017, September 2008. [Online]. Available: