The Journal of Pain
Volume 10, Issue 3 , Pages 316-322, March 2009

Hyperalgesia in Opioid-Managed Chronic Pain and Opioid-Dependent Patients

  • Justin L. Hay

      Affiliations

    • Discipline of Pharmacology, Medical School North, University of Adelaide, SA, Australia
    • Corresponding Author InformationAddress reprint requests to Dr Justin Hay, CHDR, Zernikedreef 10, 2333 CL Leiden, The Netherlands.
  • ,
  • Jason M. White

      Affiliations

    • Discipline of Pharmacology, Medical School North, University of Adelaide, SA, Australia
    • Drug and Alcohol Services South Australia, Parkside, SA, Australia
  • ,
  • Felix Bochner

      Affiliations

    • Discipline of Pharmacology, Medical School North, University of Adelaide, SA, Australia
    • Department of Clinical Pharmacology, Royal Adelaide Hospital, Adelaide, SA, Australia
  • ,
  • Andrew A. Somogyi

      Affiliations

    • Discipline of Pharmacology, Medical School North, University of Adelaide, SA, Australia
    • Department of Clinical Pharmacology, Royal Adelaide Hospital, Adelaide, SA, Australia
  • ,
  • Tim J. Semple

      Affiliations

    • Pain Management Unit, Royal Adelaide Hospital, Adelaide, SA, Australia
  • ,
  • Bruce Rounsefell

      Affiliations

    • Pain Management Unit, Royal Adelaide Hospital, Adelaide, SA, Australia

Received 28 March 2008; received in revised form 15 September 2008; accepted 7 October 2008. published online 22 December 2008.

Abstract 

This observational study aimed to determine whether pain sensitivity in patients with noncancer chronic pain, taking either methadone or morphine, is similar to patients maintained on methadone for dependence therapy, compared with a control group. Nociceptive thresholds were measured on a single occasion with von Frey hairs, electrical stimulation, and cold pressor tests. In all subjects receiving methadone or morphine, nociceptive testing occurred just before a scheduled dose. Cold pressor tolerance values in patients with noncancer, chronic pain, treated with morphine and methadone, were 18.1 ± 2.6 seconds (mean ± SEM) and 19.7 ± 2.3 seconds, respectively; in methadone-maintained subjects it was 18.9 ± 1.9 seconds, with all values being significantly (P < .05) lower than opioid-naïve subjects (30.7 ± 3.9 seconds). These results indicate that patients with chronic pain managed with opioids and methadone-maintained subjects are hyperalgesic when assessed by the cold pressor test but not by the electrical stimulation test. None of the groups exhibited allodynia as measured using the von Frey hairs. These results add to the growing body of evidence that chronic opioid exposure increases sensitivity to some types of pain. They also demonstrate that in humans, this hyperalgesia is not associated with allodynia.

Perspective

This article presents an observational study whereby the pain sensitivity of patients with chronic pain managed with opioids and opioid-maintained patients were compared with opioid-naïve patients. The results suggest that opioid use may contribute to an increase in the sensitivity to certain pain experimental stimuli.

Key words: Pain, methadone, morphine, antinociception, chronic pain

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 Supported in part by the Faculty of Health Science Small Research Grant Scheme. Justin Hay was a recipient of a University of Adelaide Postgraduate scholarship. Presented in part at the 11th World Congress on Pain (IASP), August 2005, Sydney, Australia.

PII: S1526-5900(08)00801-8

doi:10.1016/j.jpain.2008.10.003

The Journal of Pain
Volume 10, Issue 3 , Pages 316-322, March 2009