Significant pain reduction in chronic pain patients after detoxification from high-dose opioids

Michael J. Baron, MD, MPH; Paul W. McDonald, PhD

doi:10.5055/jom.2006.0041

Authors

Michael J. Baron, MD, MPH
Paul W. McDonald, PhD

DOI:

https://doi.org/10.5055/jom.2006.0041

Keywords:

opioid, tolerance, hyperalgesia, sensitization, detoxification, buprenorphine

Abstract

Opioid tolerance is a well-established phenomenon that often occurs in patients taking opioids for the treatment of chronic pain. Typically, doctors need to periodically elevate patients’ opioid doses in an attempt to manage their underlying pain conditions, resulting in escalating opioid levels with only moderate to negligible improvement in pain relief. Recently, opioid-induced hyperalgesia has been recognized as a potential form of central sensitization in which a patient’s pain level increases in parallel with elevation of his or her opioid dose. Here, we report a retrospective study of patients undergoing detoxification from high-dose opioids prescribed to treat an underlying chronic pain condition which had not resolved in the year prior. All patients were converted to ibuprofen to manage pain, with a subgroup treated with buprenorphine during detoxification. Selfreports for pain scores were taken at first evaluation, follow-up visits, and termination. Twenty-one of 23 patients reported a significant decrease in pain after detoxification, suggesting that high-dose opioids may contribute to pain sensitization via opioid-induced hyperalgesia, decreasing patient pain threshold and potentially masking resolution of the preexisting pain condition.

Author Biographies

Michael J. Baron, MD, MPH

Psychiatry, Vanderbilt University, Nashville, Tennessee.

Paul W. McDonald, PhD

Neuroscience, Booz Allen Hamilton, McLean, Virginia.

References

Cox BM: Drug Tolerance and Physical Dependence. New York: Churchill Livingstone, 1990.

Foley KM: Opioids. Neurol Clin. 1993; 11(3): 503-522.

Foley KM: Misconceptions and controversies regarding the use of opioids in cancer pain. Anticancer Drugs. 1995; 6 Suppl 3: 4-13.

Way EL, Loh HH, Shen FH: Simultaneous quantitative assessment of morphine tolerance and physical dependence. J Pharmacol Exp Ther. 1969; 167(1): 1-8.

Collett BJ: Opioid tolerance: The clinical perspective. Br J Anaesth. 1998; 81(1): 58-68.

Ruscheweyh R, Sandkuhler J: Opioids and central sensitisation: II. Induction and reversal of hyperalgesia. Eur J Pain. 2005; 9(2): 149-152.

von Zastrow M: Mechanisms regulating membrane trafficking of G protein-coupled receptors in the endocytic pathway. Life Sci. 2003; 74(2-3): 217-224.

Zuo Z: The role of opioid receptor internalization and betaarrestins in the development of opioid tolerance. Anesth Analg. 2005; 101(3): 728-734, table of contents.

Bailey CP, Connor M: Opioids: Cellular mechanisms of tolerance and physical dependence. Curr Opin Pharmacol. 2005; 5(1): 60-68.

Borgland SL: Acute opioid receptor desensitization and tolerance: Is there a link? Clin Exp Pharmacol Physiol. 2001; 28(3): 147-154.

Cochin J, Kornetsky C: Development and loss of tolerance to morphine in the rat after single and multiple injections. J Pharmacol Exp Ther. 1964; 145: 1-10.

Houde RW: The analgesic connection: The Nathan B. Eddy memorial lecture. NIDA Res Monogr. 1984; 55: 4-13.

Kaneto H, Kosaka N, Hirota N: Timing of cycloheximide administration and inhibition of the development of analgesic tolerance to morphine. Life Sci. 1982; 31(20-21): 2351-2354.

Loh HH, Shen FH, Way EL: Inhibition of morphine tolerance and physical dependence development and brain serotonin synthesis by cycloheximide. Biochem Pharmacol. 1969; 18(10): 2711-2721.

Blanchet C, Sollini M, Luscher C: Two distinct forms of desensitization of G-protein coupled inwardly rectifying potassium currents evoked by alkaloid and peptide mu-opioid receptor agonists. Mol Cell Neurosci. 2003; 24(2): 517-523.

Patel MB, Patel CN, Rajashekara V, et al.: Opioid agonists differentially regulate mu-opioid receptors and trafficking proteins in vivo. Mol Pharmacol. 2002; 62(6): 1464-1470.

Tanowitz M, von Zastrow M: A novel endocytic recycling signal that distinguishes the membrane trafficking of naturally occurring opioid receptors. J Biol Chem. 2003; 278(46): 45978-45986.

Bot G, Blake AD, Li S, et al.: Fentanyl and its analogs desensitize the cloned mu opioid receptor. J Pharmacol Exp Ther. 1998; 285(3): 1207-1218.

Liu JG, Liao XP, Gong ZH, et al.: Methadone-induced desensitization of the delta-opioid receptor is mediated by uncoupling of receptor from G protein. Eur J Pharmacol. 1999; 374(2): 301-308.

Celver J, Xu M, Jin W, et al.: Distinct domains of the mu-opioid receptor control uncoupling and internalization. Mol Pharmacol. 2004; 65(3): 528-537.

Ossipov MH, Lai J, King T, et al.: Underlying mechanisms of pronociceptive consequences of prolonged morphine exposure. Biopolymers. 2005; 80(2-3): 319-324.

Vanderah TW, Suenaga NM, Ossipov MH, et al.: Tonic descending facilitation from the rostral ventromedial medulla mediates opioid-induced abnormal pain and antinociceptive tolerance. J Neurosci. 2001; 21(1): 279-286.

Celerier E, Laulin J, Larcher A, et al.: Evidence for opiateactivated NMDA processes masking opiate analgesia in rats. Brain Res. 1999; 847(1): 18-25.

Mao J, Mayer DJ: Spinal cord neuroplasticity following repeated opioid exposure and its relation to pathological pain. Ann N Y Acad Sci. 2001; 933: 175-184.

Ossipov MH, Lai J, Vanderah TW, et al.: Induction of pain facilitation by sustained opioid exposure: Relationship to opioid antinociceptive tolerance. Life Sci. 2003; 73(6): 783-800.

Manlandro JJ Jr: Buprenorphine for office-based treatment of patients with opioid addiction. J Am Osteopath Assoc. 2005; 105(6 Suppl 3): S8-S13.

Sjogren P, Jensen NH, Jensen TS: Disappearance of morphine-induced hyperalgesia after discontinuing or substituting morphine with other opioid agonists. Pain. 1994; 59(2): 313-316.

Cowan DT, Allan L, Griffiths P: A pilot study into the problematic use of opioid analgesics in chronic non-cancer pain patients. Int J Nurs Stud. 2002; 39(1): 59-69.

Hoffmann O, Plesan A, Wiesenfeld-Hallin Z: Genetic differences in morphine sensitivity, tolerance and withdrawal in rats. Brain Res. 1998; 806(2): 232-237.

Yu Y, Zhang L, Yin X, et al.: Mu opioid receptor phosphorylation, desensitization, and ligand efficacy. J Biol Chem. 1997; 272(46): 28869-28874.

Ward TN: Medication overuse headache. Prim Care. 2004; 31(2): 369-380, vii.

Mahowald ML, Singh JA, Majeski P: Opioid use by patients in an orthopedics spine clinic. Arthritis Rheum. 2005; 52(1): 312-321.