Updates on Smoking and Low Back Pain
An estimated 1 in 5 adults in the United States uses tobacco products every day or some days. This equates to 50 million people and 21.3% of the overall population.1 Smoking is more common among men (26.2%) than women (15.4%) and is most common among adults aged 25 to 44 years (25.2%).1 Tobacco use remains the leading cause of preventable death in the United States, accounting for more than 480,000 deaths each year.2 In addition, more than 16 million Americans suffer from a smoking-related disease, including cancer, and respiratory and vascular diseases.2
Interestingly, the prevalence of tobacco use is nearly 2-fold higher among patients with chronic pain.3-5 The reasons for this increased prevalence are believed to be related to many factors, encompassing both behavioral and biological mechanisms. This review will cover current knowledge on the biological mechanisms and pathophysiology behind the relationship between smoking and chronic pain. The behavioral mechanisms are discussed in a Q&A with Joseph W. Ditre, PhD.
Cigarettes contain many compounds that produce physiologic effects, but this review focuses on nicotine, which is the most widely studied of these compounds and is believed to play a role in pain modulation. Nicotine has analgesic properties that, at first, can help relieve acute pain. However, over time, nicotine can alter pain processing and contribute to the development of chronic pain and greater pain intensity. This paradox is an important aspect of both acute and chronic pain management for patients who use tobacco products.
Mechanism of Nicotine Action
A variety of factors are believed to contribute to the analgesic effects of short-term exposure to nicotine.
First, nicotine is an agonist of nicotinic acetylcholine receptors (nAChRs), which are found throughout the peripheral and central nervous system, and notably in brain regions associated with pain transmission, such as the dorsal horn, locus ceruleus, and thalamus.6 Specifically, nicotine acts on the α3β4 ganglion type in the autonomic ganglia and adrenal medulla, and the α4β2 nicotinic receptors in the central nervous system.6,7 The increased binding of nAChRs produces central antinociceptive effects that activate the spinal cord descending pain-inhibitory pathways, resulting in discharge of epinephrine from the adrenal medulla and catecholamines from sympathetic nerve endings.8-10
Activation of nAChRs also potentiates the release of other neurotransmitters, such as dopamine, that play a role in nicotine-mediated analgesia.8,11 This increased stimulation of dopamine also activates the mesolimbic dopamine reward system, which increases the importance of incentive cues associated with nicotine use.6 Through this reward system, painful stimuli can become a conditioned cue for smoking.6 Interestingly, activation of nAChRs is similar to activation of opioid receptors in that both stimulate the release of dopamine in the nucleus accumbens, which mediates the rewarding effects of nicotine and plays a role in pain perception.8,12,13
Second, the antinociceptive effects of nicotine also may be mediated by activation of endogenous opioid systems.14,15 Smoking stimulates the release of beta-endorphins, which are endogenous opioid polypeptide compounds that are similar to opioids in their analgesic effects.16,17 The more cigarettes smoked per day, the higher the plasma concentration of beta-endorphins.6,18
Third, smoking causes changes in the neuroendocrine system that could modulate pain perception. In general, the stress response (sympathetic and hypothalamic-pituitary-adrenal [HPA] activation)7 causes a decrease in pain perception.8,19 However, this stress response is blunted in chronic smokers, possibly because of attenuated modulation of endogenous opioids on the HPA.19
Fourth, pressor actions on the cardiovascular system have been hypothesized to play a role in the analgesic effect of nicotine. Some studies suggest that passive smoking and smoking cigarettes increases blood pressure, which in turn has been linked to reduced pain sensitivity.6,20-23
Other proposed mechanisms for the analgesic effects of nicotine include attentional narrowing, release of norepinephrine and serotonin, g-aminobutyric acid (GABA) receptor activity, regulation of inflammatory responses, and suppression of pain-related evoked potentials.6,24-28
While all of these analgesic effects of nicotine occur with brief exposure to nicotine, chronic nicotine exposure is linked to nAChR desensitization and tolerance29-31 and changes in the endogenous opioid system that may alter pain processing.31
Smoking and Chronic Pain Studies
It is important to differentiate the effects of nicotine in experimental versus epidemiologic studies. While experimental studies suggest an analgesic and antinociceptive effect of tobacco use in acute pain, epidemiologic studies point to a causal association between smoking and chronic pain.
Experimental studies point to analgesic and antinociceptive effects in acute pain. For example, in early research by Tripathi et al, the researchers assessed the analgesic effect of nicotine by measuring tail-flick latency in rats and mice.32 Brain levels of nicotine reached a maximum at 10 minutes, whereas antinociception was maximal at 2 minutes. Tachyphylaxis to antinociception developed in 10 minutes and lasted up to 14 hours. In a 1998 study, Jamner et al found that nicotine increased pain threshold and tolerance ratings of men but had no effect on pain ratings of women.33 In 2004, Flood et al studied the effects of intranasal nicotine for postoperative pain treatment. They found that patients treated with nicotine reported lower pain scores during the first hour after surgery and less pain 24 hours after surgery, and used half the amount of morphine as the control group.34
While short-term exposure to nicotine appears to have antinociceptive effects, chronic exposure to nicotine may change pain perception due to receptor desensitization. Indeed, studies suggest that nicotine withdrawal increases pain sensitivity and blunts stress response in chronic smokers in experimental pain tests, and that this effect drives excessive nicotine use via corticotropin-releasing factor signaling pathways.35,36
While an early landmark meta-analysis by Leboeuf-Yde did not show a consistent statistically significant positive association between smoking and low back pain (LBP) in studies published between 1974 and 1996,37 a resurgence of interest in this issue has produced more research in this field. Numerous recent studies have demonstrated an association between smoking and the prevalence of a variety of chronic pain conditions.38-41 In addition, chronic pain patients who smoke have greater pain intensity than those who do not smoke.42