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.

Fig. 1

Correlations between pain-tolerance time and distress and pain intensity. a Negative correlations between pain-tolerance time and distress in OAs and controls (r=−0.359, p=0.008 for OAs and r=−0.427, p=0.003 for the controls). b Correlations between pain-tolerance time and pain intensity in OAs and controls (r=−0.171, p=0.216 for OAs and r=−0.418, p=0.004 for the controls). Only controls showed significant negative correlations between pain-tolerance time and pain intensity. *p<0.01

Fig. 2

Comparison of cue-induced drug craving and anxiety between pain-sensitive and pain-tolerant opiate addicts. a Pain-sensitive opiate addicts reported greater craving increases than pain-tolerant opiate addicts when exposed to heroin-related cues. b Pain-sensitive opiate addicts did not show greater anxiety increases than pain-tolerant opiate addicts when exposed to heroin-related cues. *p<0.01 between PS and PT

Fig. 3

Correlations between cue-induced craving changes and pain-induced distress in OAs. OAs showed a positive correlation between craving changes and ratings of pain distress (r=0.33, p=0.01). *p<0.05