, 2008; Sallette et al., 2005) such that pain perception is altered (Perkins et al., 1994; Silverstein, 1982). Second, smoking may worsen disease processes, such as osteoporosis, which may cause pain (An et al., 1994; Glassman et al., 2000; Law & Hackshaw, 1997). Third, Veliparib clinical smoking may be a coping strategy utilized to manage anxiety and stress induced by pain such that pain may contribute to the maintenance of smoking behavior (Ditre, Heckman, Butts, & Brandon, 2010). Finally, smoking is associated with other factors that can affect pain such as depression. Symptoms of depression are more prevalent in smokers compared with non smokers (Breslau, Peterson, Schultz, Chilcoat, & Andreski, 1998; Brown, Madden, Palenchar, & Cooper-Patrick, 2000; Murphy et al.

, 2003), and smoking predicts the onset of depression as well as exacerbates existing symptoms of depression (Klungsoyr, Nygard, Sorensen, & Sandanger, 2006; Pasco et al., 2008). Given that the mechanisms underlying the association between smoking and pain are not known, it is difficult to predict how abstinence from smoking might affect pain. Several considerations may apply. In experimental humans and animal studies, smoking can have acute analgesic effects in subjects without chronic pain (Jamner et al., 1998; Perkins et al., 1994), which could favor pain exacerbation when exposure to smoke is eliminated. However, it is not known whether smoking a cigarette changes pain perception in smokers with chronic pain. Animal models suggest that nicotine withdrawal is associated with increased sensitivity to pain stimuli (Anderson et al.

, 2004; Biala et al., 2005; Schmidt et al., 2001; Yang et al., 1992). If smoking represents a coping strategy for pain, abstinence may result in the loss of a means of dealing with pain, which may increase the reporting of pain. To the extent that the body may recover from altered pain perception and structural damaged caused by smoking, long-term abstinence may improve pain symptoms. If smoking is just an indicator of other causal factors for pain such as depression, abstinence may have little effect. We did not observe a consistent effect of smoking abstinence on pain in this analysis of data of older adults, suggesting that (a) any changes in pain perception or structural damage caused by smoking are not reversible, (b) smoking per se does not affect chronic pain but rather is associated with other factors such as depression that are causal for pain exacerbation, or (c) that there is no net effect of changes in multiple factors that contribute to a relationship between smoking and pain.

To our knowledge, no prior study has directly investigated the relationship between smoking cessation and changes Entinostat in pain. However, other studies that have included former smokers suggest that chronic pain is also more common in this subgroup of adults (Jakobsson, 2008; John, Alte, et al., 2006; Palmer et al., 2003).