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

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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.

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Acknowledgments

This work was supported in part by the grant from the National Basic Research Program of China (973 Program, 2007CB512302 and 2009CB522004), the National High Technology Research and Development Program of China (863 Program, 2006AA02Z4D1), and the China–Canada Joint Health Research Program (No: 30611120528). We thank Xiaoli Zhang, Jingjie Yu, and Tangying Lu for technical assistant and Yu Liu for helpful comments on an early version of the manuscript.

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Authors and Affiliations

  1. National Institute on Drug Dependence, Peking University, 38, Xue Yuan Road, HaiDian District, Beijing, 100083, China

    Zhen-Yu Ren, Jie Shi, Jun Wang & Lin Lu

  2. Intramural Research Program, National Institute on Drug Abuse, National Institutes of Health, Baltimore, MD, 21224, USA

    David H. Epstein

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  1. Zhen-Yu Ren
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  2. Jie Shi
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  4. Jun Wang
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  5. Lin Lu
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Correspondence to Lin Lu.

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Ren, ZY., Shi, J., Epstein, D.H. et al. Abnormal pain response in pain-sensitive opiate addicts after prolonged abstinence predicts increased drug craving. Psychopharmacology 204, 423–429 (2009). https://doi.org/10.1007/s00213-009-1472-0

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  • DOI: https://doi.org/10.1007/s00213-009-1472-0

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