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

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).

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.

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.

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).

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.