Abstract
Evidence suggests that patients on opiate maintenance therapy for the treatment of
addiction present with opioid-induced hyperalgesia. This study compared the experimental
(cold-pressor, electrical stimulation) pain responses of 82 treatment-seeking heroin-dependent
adults, randomized to methadone (METH, n = 11) or buprenorphine (BUP, n = 64) therapy,
with matched drug free controls (n = 21). Heroin-dependent participants were evaluated
at baseline (treatment entry), medication (METH or BUP) stabilization (4–8 weeks),
and chronic administration (12–18 weeks), at trough (just prior to dosing) and peak
(3 hours after dosing) plasma levels. Collection of the control group’s pain responses
occurred twice during a single session, 3 hours apart. Baseline comparisons indicate
that heroin-dependent individuals demonstrate significantly shorter latencies to threshold
and tolerance for cold-pressor pain than the control group. Across pain stimuli and
time points, little change in pain responses was found over time, the exception being
cold pressor pain tolerance, for which hyperalgesia significantly increased at trough
METH/BUP levels in both groups as they stabilized in treatment. We conclude that heroin-dependent
individuals are hyperalgesic, and that once stabilized in treatment, are not different
in pain responses regardless of treatment agent. The effects of nonpharmacologic therapy
and previous heroin use may explain increased hyperalgesia found with treatment.
Perspective
To better understand the clinical phenomenon of opioid-induced hyperalgesia, this
article describes experimental pain responses of heroin-dependent participants both
prior to and over the course of maintenance therapy with methadone or buprenorphine.
Hyperalgesia is present with illicit and treatment opioid use, and does not appear
to appreciably improve over the course of treatment.
Key words
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References
- Acute pain management for patients receiving maintenance methadone or buprenorphine therapy.Ann Intern Med. 2006; 17: 127-134
- Opioid-induced hyperalgesia; A qualitative systematic review.Anesthesiology. 2006; 104: 570-587
- Methadone maintenance patients are cross tolerant to the antinociceptive effects of very high plasma morphine concentrations.Pain. 2006; 120: 267-275
- Comparison of Beck Depression Inventories -IA and -II in psychiatric outpatients.J Pers Assess. 1996; 67: 588-597
- A family-based investigation of cold pain tolerance.Pain. 2008; 138: 111-118
- Long-lasting hyperalgesia induced by fentanyl in rats: Preventive effect of ketamine.Anesthesiology. 2000; 92: 465-472
- Opioid tolerance and hyperalgesia.Med Clin North Am. 2007; 91: 199-211
- Opioid-induced hyperalgesia in humans: Molecular mechanisms and clinical considerations.Clin J Pain. 2008; 24: 79-96
- Mechanisms of opioid-induced pain and antinociceptive tolerance: Signal transduction.Pain. 2002; 95: 287-288
- Cold-pressor pain tolerance in opiate and cocaine abusers: Correlates of drug type and use status.J Pain Symptom Manage. 1994; 9: 462-473
- Pain responses in methadone-maintained opioid abusers.J Pain Symptom Manage. 2000; 20: 237-245
- Pain intolerance in opioid-maintained former opiate addicts: Effect of long-acting maintenance agent.Drug Alcohol Depend. 2001; 63: 139-146
- Effects of aspirin on detection and tolerance of electric shock.J Appl Physiol. 1965; 20: 1052-1055
- Hyperalgesic responses in methadone maintenance patients.Pain. 2001; 90: 91-96
- Methadone maintenance patients are cross-tolerant to the antinociceptive effects of morphine.Pain. 2001; 93: 155-163
- Same incidence of adverse drug events after codeine administration irrespective of the genetically determined differences in morphine formation.Pain. 1998; 76: 27-33
- Do opioids induce hyperalgesia in humans? An evidence-based structured review.Pain Med. 2009; 10: 829-839
- Rounsefell: Hyperalgesia in opioid-managed chronic pain and opioid-dependent patients.J Pain. 2009; 10: 316-322
- Pain perception in drug-free and in methadone-maintained human ex-addicts.Proc Soc Exp Biol Med. 1979; 162: 392-395
- The impact of opioid-induced hyperalgesia for postoperative pain.Best Pract Res Clin Anaesthesiol. 2007; 21: 65-83
- A comprehensive review of opioid-induced hyperalgesia.Pain Physician. 2011; 14: 145-161
- A murine model of opioid-induced hyperalgesia.Brain Res Mol Brain Res. 2001; 86: 56-62
- Persistent analgesia in former opiate addicts is resistant to blockade of endogenous opioids.Biol Psychiatry. 1997; 42: 962-964
- Methadone maintenance therapy versus no opioid replacement therapy for opioid dependence.Cochrane Database Syst Rev. 2009; 8: CD002209
- Buprenorphine maintenance versus placebo or methadone maintenance for opioid dependence.Cochrane Database Syst Rev. 2008; 16: CD002207
- An improved diagnostic instrument for substance abuse patients: The Addiction Severity Index.J Nervous Mental Dis. 1980; 168: 26-33
- Pain management in the addicted patient: Practical considerations.Nurs Outlook. 2000; 48: 81-85
- Individual differences in pain sensitivity: Measurement, causation, and consequences.Pain. 2009; 10: 231-237
- Significantly higher methadone dose for methadone maintenance treatment (MMT) patients with chronic pain.Pain. 2005; 113: 340-346
- The differential effect of methadone dose and of chronic pain on pain perception of former heroin addicts receiving methadone maintenance treatment.J Pain. 2011; 12: 41-50
- Physical pain and associated clinical characteristics in treatment-seeking patients in four substance use disorder treatment modalities.Am J Addict. 2008; 17: 121-125
- Abnormal heat and pain perception in remitted heroin dependence months after detoxification from methadone-maintenance.Drug Alcohol Depend. 2008; 95: 237-244
- Opioids and abnormal pain perception: New evidence from a study of chronic opioid addicts and healthy subjects.Drug Alcohol Depend. 2006; 82: 218-223
- Prevalence and characteristics of chronic pain among chemically dependent patients in methadone maintenance and residential treatment facilities.JAMA. 2003; 289: 2370-2378
- Comparison of the cold pressor test and contact thermode-delivered cold stimuli for the assessment of cold pain sensitivity.J Pain. 2010; 11: 728-736
- Treatment of pain in methadone-maintained patients.Mt Sinai J Med. 2000; 67: 412-422
- The World Federation of Societies of Biological Psychiatry (WFSBP) guidelines for the biological treatment of substance use and related disorders. Part 2: Opioid dependence.World J Biol Psychiatry. 2011; 12: 160-187
- Manual for the State-Trait Anxiety Inventory.Consulting Psychologists Press, Inc., Menlo Park, CA1983
- Concentric shock electrode for pain stimulation.Psychophysiology. 1965; 1: 296-298
- Response of experimental pain to analgesic drugs. II. Codeine and placebo.Clin Pharmacol Ther. 1966; 7: 323-331
Article Info
Publication History
Published online: March 19, 2012
Accepted:
January 13,
2012
Received in revised form:
December 19,
2011
Received:
August 13,
2011
Footnotes
Funding for study expenses and subject payment was provided by NIDA grant DA13706 .
No conflicts of interest exist.
Identification
Copyright
© 2012 American Pain Society. Published by Elsevier Inc. All rights reserved.
