Abnormal pain response in pain-sensitive opiate addicts after prolonged abstinence predicts increased drug craving

Abstract

Rationale Craving is a primary feature of opiate addiction and is clinically significant because of its potential to trigger opiate use and relapse. Opiate use can also produce abnormal pain perception. We predicted that for opiate addicts (OAs), there may be an association between these two major features of addiction (drug craving and abnormal pain responses). Objectives To examine pain responses in abstinent opiate addicts in comparison with healthy controls using a cold-pressor test (CPT) and investigate the correlations of cue-induced drug craving with pain responses. Material and methods Fifty-four abstinent OAs and 46 healthy subjects participated in the CPT, and the OAs were also exposed to heroin-related cues the day before the pain test. Outcome measures included pain-tolerance time, VAS ratings of pain intensity and distress, and (in the cue-exposure procedure) VAS ratings of heroin craving and anxiety. Results In the CPT, abstinent addicts showed shorter pain-tolerance time (85.1±14.1 s vs. 133.7±16.7 s, p<0.05) and higher ratings of pain distress (61±3.2 vs. 45.6±3.2, p< 0.01) compared to healthy controls. When we divided the addicts and controls into pain-sensitive (PS) and pain-tolerant (PT) groups by dichotomizing each group in terms of pain-tolerance time, we again found differences between the two PS groups (37.3±3.5 s vs. 57.4±5.1 s, p<0.01 for pain-tolerance time; 66.7±3.2 vs. 52.4±3.3, p<0.01 for distress ratings). For all participants, pain-tolerance time was negatively correlated with VAS ratings for pain intensity and distress. More importantly, the PS addicts reported greater cue-induced craving than the PT addicts (17.8±2.2 vs. 4.5±4.2, p<0.05). For the addict group as a whole, pain distress (the affective aspect of pain) was positively correlated with intensity of cue-induced craving measured on a different day (r=0.33, p=0.01). Conclusions A hyperalgesic state persists for at least 5 months in abstinent OAs and is predictive of cue-induced craving. Longitudinal research is needed to clarify the direction of causation between hyperalgesia and opiate addiction.

Dynamic risk factors in the misuse of opioid analgesics

“…A study of pain responses in opioid addicts entering a detoxification program versus healthy controls found significant differences in cold pressor tests (latency, visual analog scale score, tolerance) both at baseline and 28 days after opioid detoxification, indicating that pain differences persisted even after opioids were discontinued [81]. Another study of 54 opioid addicts who had discontinued opioids compared to 46 health subjects revealed former opioid addicts had hyperalgesic responses to pain that persisted at least 5 months after opioid abstinence [82].…”

Clarifying the roles of homeostasis and allostasis in physiological regulation.

“…While clinical research on individuals with a history of opioid drug abuse has inherent limitations (e.g., non-random assignment to drug use history), this corpus of work nonetheless illustrates how these sign reversals are not easily explained by common homeostatic views of adaptation (Compton, 1994; Compton, Canamar, Hillhouse, & Ling, 2012; Compton, Charuvastra, & Ling, 2001; Ren, Shi, Epstein, Wang, & Lu, 2009). For example, Compton found that cold-pressor pain tolerance counter-intuitively decreases as methadone dose increases (1994).…”

“…Chronic methadone users report maximal pain sensitivity at the time that they have the peak concentrations of the analgesic opioid (i.e., the increased pain sensitivity cannot be explained as a withdrawal effect from a waning drug concentration), and this is thought to be indicative of an over-activated corrective response. As another example, opiate addicts continue to make hyperalgesic responses, despite being abstinent from opioids for at least 5 months, suggesting that these responses are persistent and not easily deactivated even though the initial eliciting perturbation is no longer present (Ren et al, 2009). …”

Subliminal (latent) processing of pain and its evolution to conscious awareness

“…There are a number of examples but three illustrate the notion: (a) methadone addicts who have given up their addiction experience increased pain sensitivity to experimental pain years after halting their opioid use (Ren et al, 2009); (b) migraine patients who take opioids have an increased risk of disease chronification (Bigal and Lipton, 2008b); (c) chronic pain patients taking opioids may have so called opioid induced hyperalgesia (Lee et al, 2011), which probably relates to a process of pain ‘enhancement’ (hyperalgesia). Ongoing hyperalgesia may be a pre-determinant of more complex changes that lead to pain chronification (Woolf, 2011).…”