Smoking-induced nociception.

described multiple potential factors whereby smoking may contribute to pain. Smith (5) has postulated a potential novel mechanism whereby smoking may contribute to inflammatory pain via its inhibitory actions on an enzyme known as leukotriene A4 hydrolase (LTA4H), --an action on the peptidase site of LTA4H revealed by Snelgrove et al(6). Epidemiologic studies have reported an association between smoking and low back pain (7,8). Leboeuf-Yde et al (9) performed a systematic literature review on the association between smoking and low back pain based on 47 studies published between 1974 and 1996. Many, but not all, studies find a positive association between smoking and low back pain. Goldberg et al. reviewed publications from 1976 through mid-1997 on the association between smoking and nonspecific back pain and also found that smoking is associated with nonspecific back pain in some, but not all, of the studies (10). Other studies suggest that among those with chronic pain, smokers complain of greater pain intensity and an increased number of painful sites (11,12). Shi and colleagues have noted that many factors may influence the relationship between smoking and chronic pain including: 1) smoking-induced altered processing of pain, chronic exposure to cigarette smoke (chronic smoke exposure may change pain perception in smokers compared with nonsmokers]) (Smokers may perceive a given stimulus as more painful (at least while deprived of cigarettes) and may smoke to relieve increased pain perceptions caused by incipient nicotine withdrawal when nicotine blood levels fall (e.g., during sleep) 2) smoking-induced neuroendocrine system modulation of apin perception; 3) smoking-induced structural damage to other systems/processes [interference with bone and connective tissue homeostasis, interference with wound healing, interference with oxygen delivery]; 4) smoking-induced mood changes [association with depression]; 5) smoking associated psychosocial factors, and/or 6) smoking associated opioid use and interaction with opioids or opioidergic systems/pathways. [Opioid-related pathways may modulate both the analgesic effects of nicotine and the reinforcing properties of smoking that contribute to addiction] (Exposure to cigarette smoke may also alter the pharmacokinetics of opioids) (4). Although the review of Shi et al. concentrates on nicotine-modulation of pain they appropriately point out that “any of the approximately 3,000 other constituents of cigarette smoke may also be involved in the development of painful conditions (4). “Chronic exposure to carbon monoxide increases the level of heme oxygenase (13,14); thus “the possible involvement of the heme oxygenase-carbon monoxide system in the susceptibility of smokers to chronic pain deserves further study” (4). Smith has proposed a novel potential mechanism in which smoking may facilitate inflammatory pain that appears to be unrelated to nicotine or carbon monoxide (5). Leukotriene B4 (LTB4) is largely derived from the action of 5-lipoxygenase on arachidonic acid in leukocytes (15,16). LTB4 may evoke profound hyperalgesia on intradermal injection into the dorsum of the rat’s hindpaw (17). LTB4 induced-hyperalgesia is distinguished from that of PGE2 by a dependence Editorial