Opioid-induced hyperalgesia: Pathophysiology and clinical implications
DOI:
https://doi.org/10.5055/jom.2008.0017Keywords:
opioids, pain, opioid-induced hyperalgesia, intensivistsAbstract
Background: Opioid-induced hyperalgesia (OIH) refers to a phenomenon whereby opioid administration results in a lowering of pain threshold, clinically manifest as apparent opioid tolerance, worsening pain despite accelerating opioid doses, and abnormal pain symptoms such as allodynia.Aim: The current review, while providing a clinically oriented updated overview on the pathophysiology of OIH, focuses predominantly on evidence-based clinical and management aspects of this important and often baffling phenomenon.
Method: Online and manual search using key words such as opioid-induced hyperalgesia, opioid-induced abnormal pain sensitivity, opioid hyperalgesia, opioidinduced paradoxical pain, or opioid-induced abnormal pain, followed by full-text access and further crossreferencing.
Results: The underlying pathophysiology of this phenomenon, although still unclear, appears to be related to an opioid-induced imbalance between the internal antinociceptive and pronociceptive systems. Clinical differentiation of an apparent opioid tolerance state includes OIH. Once diagnosed or provisionally considered, treatment strategies could include opioid dose reduction, opioid rotation, use of agents with NMDA receptor antagonism, and a properly timed coxib.
Conclusion: Despite initial skepticism and reservations, the phenomenon of OIH in humans is now accepted a clinical reality and a challenge faced by anesthesiologists, intensivists, pain specialists, and other workers in a diverse range of settings from perioperative care to palliative care medicine.
References
Simmonet G, Rivat C: Opioid-induced hyperalgesia: Abnormal or normal pain. NeuroReport. 2003; 14: 1-7.
Mao J: Opioid-induced abnormal pain sensitivity: Implications in clinical opioid therapy. Pain. 2002; 100: 213-217.
Xu X-J, Colpaert F, Wiesenfeld-Hallin Z: Opioid hyperalgesia and tolerance versus 5-HT1a receptor-mediated inverse tolerance. Trends Pharmacol Sci. 2003; 24: 634-639.
Mercadante S, Ferrera P, Villari P, et al.: Hyperalgesia: An emerging iatrogenic syndrome. J Pain Symptom Manage. 2003; 26: 769-775.
Ossipov MH, Lai J, King T, et al.: Antinociceptive and nociceptive actions of opioids. J Neurobiol. 2004; 61: 126-148.
Fine PG: Opioid insights: Opioid-induced hyperalgesia and opioid rotation. J Pain Palliat Care Pharmacother. 2004; 18: 75- 79.
Ali NM: Hyperalgesic response in a patient receiving high concentrations of spinal morphine. Anesthesiology. 1986; 65: 449.
De Conno F, Caraceni A, Martini C, et al.: Hyperalgesia and myoclonus with intrathecal infusion of high-dose morphine. Pain. 1991; 47: 337-339.
Devulder J: Hyperalgesia induced by high-dose intrathecal sufentanil in neuropathic pain. J Neurosurg Anesthesiol. 1997; 9: 146-148.
Wilson GR, Reisfield GM: Morphine hyperalgesia: A case report. Am J Hosp Palliat Care. 2003; 20: 459-461.
Chung KS, Carson S, Glassman D, et al.: Successful treatment of hydromorphone-induced neurotoxicity and hyperalgesia. Conn Med. 2004; 68: 547-549.
Koppert W: Opioid-induced hyperalgesia. Pathophysiology and clinical relevance. Anaesthesist. 2004; 53: 455-466.
Angst MS, Clark JD: Opioid-induced hyperalgesia. A qualitative systematic review. Anesthesiology. 2006; 104: 570-587.
Wilder-Smith OHG, Arendt-Nielsen L: Postoperative hyperalgesia. Its clinical importance and relevance. Anesthesiology. 2006; 104: 601-607.
Chang G, Chen L, Mao J: Opioid tolerance and hyperalgesia. Med Clin N Am. 2007; 91: 199-211.
Koppert W, Schmelz M: The impact of opioid-induced hyperalgesia for postoperative pain. Best Pract Res Clin Anaesthesiol. 2007; 21: 65-83.
Mercadante S. Opioid rotation for cancer pain: Rationale and clinical aspects. Cancer. 1999; 86: 1856-1866.
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: 279-286.
Heinricher MM, Neubert MJ: Neural basis for the hyperalgesic action of cholecystokinin in the rostral ventromedial medulla. J Neurophysiol. 2004; 92: 1982-1989.
Vera-Portocarrero LP, Zhang ET, King T, et al.: Spinal NK-1 receptor expressing neurons mediate opioid-induced hyperalgesia and antinociceptive tolerance via activation of descending pathways. Pain. 2007; 129: 35-45.
Liang DY, Liao G, Wang J, et al.: A genetic analysis of opioid- induced hyperalgesia in mice. Anesthesiology. 2006; 104: 1054-1062.
Liang DY, Liao G, Lighthall GK, et al.: Genetic variants of the P-glycoprotein gene Abcb1b modulate opioid-induced hyperalgesia, tolerance and dependence. Pharmacogenet Genomics. 2006; 16: 825-835.
Juni A, Klein G, Kest B: Morphine hyperalgesia in mice is unrelated to opioid activity, analgesia, or tolerance: evidence for multiple diverse hyperalgesic systems. Brain Res. 2006; 1070: 35-44.
Juni A, Klein G, Pintar JE, et al.: Nociception increases during opioid infusion in opioid receptor triple knock-out mice. Neuroscience. 2007; 147: 439-444.
Koppert W, Sittl R, Scheuber K, et al.: Differential modulation of remifentanil-induced analgesia and postinfusion hyperalgesia by S-ketamine and clonidine in humans. Anesthesiology. 2003; 99: 152-159.
Wilder-Smith OH, Tassonyi E, Crul BJ, et al.: Quantitative sensory testing and human surgery: Effects of analgesic management on postoperative neuroplasticity. Anesthesiology. 2003; 98: 1214-1222.
Kawamata M, Watanabe H, Nishikawa K, et al.: Different mechanisms of development and maintenance of experimental incision-induced hyperalgesia in human skin. Anesthesiology. 2002; 97: 550-559.
Luginbuhl M, Gerber A, Schnider TW, et al.: Modulation of remifentanil-induced analgesia, hyperalgesia, and tolerance by small-dose ketamine in humans. Anesth Analg. 2003; 96: 726-732.
Joly V, Richebe P, Guignard B, et al.: Remifentanil-induced postoperative hyperalgesia and its prevention with small-dose ketamine. Anesthesiology. 2005; 103: 147-155.
Edwards RR, Sarlani E, Wesselmann U, et al.: Quantitative assessment of experimental pain perception: Multiple domains of clinical relevance. Pain. 2005; 114: 315-319.
Reznikov I, Pud D, Eisenberg E: Oral opioid administration and hyperalgesia in patients with cancer or chronic nonmalignant pain. Br J Clin Pharmacol. 2005; 60: 311-318.
Siao P, Cros DP: Quantitative sensory testing. Phys Med Rehabil Clin N Am. 2003; 14: 261-286.
Chong PS, Cros DP: Technology literature review: Quantitative sensory testing. Muscle Nerve. 2004; 29: 734-747.
Mitra S, Sinatra RS: Perioperative management of acute pain in the opioid dependent patient. Anesthesiology. 2004; 101: 212-227.
Visser E, Schug SA: The role of ketamine in pain management. Biomed Pharmacother. 2006; 60: 341-348.
Ilkjaer S, Bach LF, Nielsen PA, et al.: Effect of preoperative oral dextromethorphan on immediate and late postoperative pain and hyperalgesia after total abdominal hysterectomy. Pain. 2000; 86: 19-24.
Schmid RL, Sandler AN, Katz J.: Use and efficacy of lowdose ketamine in the management of acute postoperative pain: A review of current techniques and outcomes. Pain. 1999; 82: 111-125.
Weinbroum AA, Gorodezky A, Nirkin A, et al.: Dextromethorphan for the reduction of immediate and late postoperative pain and morphine consumption in orthopedic oncology patients: A randomized, placebo-controlled, double-blind study. Cancer. 2002; 95: 1164-1170.
Weinbroum AA, Bender B, Bickels J, et al.: Preoperative and postoperative dextromethorphan provides sustained reduction in postoperative pain and patient-controlled epidural analgesia requirement: A randomized, placebo-controlled, double-blind study in lower-body bone malignancy-operated patients. Cancer. 2003; 97: 2334-2340.
Weinbroum AA, Gorodezky A, Niv D, et al.: Dextromethorphan attenuation of postoperative pain and primary and secondary thermal hyperalgesia. Can J Anaesth. 2001; 48: 167-174.
Katz NP: Morphidex (MS:DM) double-blind, multiple-dose studies in chronic pain patients. J Pain Symptom Manage. 2000; 19: S37-S41.
Frymoyer AR, Rowbotham MC, Petersen KL: Placebocontrolled comparison of a morphine/dextromethorphan combination with morphine on experimental pain and hyperalgesia in healthy volunteers. J Pain. 2007; 8: 19-25.
Duedahl TH, Dirks J, Petersen KB, et al.: Intravenous dextromethorphan to human volunteers: Relationship between pharmacokinetics and anti-hyperalgesic effect. Pain. 2005; 113: 360-368.
Morley JS, Watt JW, Wells JC, et al.: Methadone in pain uncontrolled by morphine. Lancet. 1993; 342: 1243.
Williams PI, Sarginson RE, Ratcliffe JM: Use of methadone in the morphine-tolerant burned paediatric patient. Br J Anaesth. 1998; 80: 92-95.
Mercadante S, Arcuri E: Hyperalgesia and opioid switching. Am J Hosp Palliat Care. 2005; 22: 291-294.
Axelrod DJ, Reville B: Using methadone to treat opioidinduced hyperalgesia and refractory pain. J Opioid Manage. 2007; 3: 113-114.
De Kock MF, Crochet B, Morimont C, et al.: Intravenous or epidural clonidine for intra and postoperative analgesia. Anesthesiology. 1993; 79: 525-531.
De Kock MF, Pichon G, Scholtes JL: Intraoperative clonidine enhances postoperative morphine patient-controlled analgesia. Can J Anaesth. 1992; 39: 537-544.
Fairbanks CA, Wilcox GL: Spinal antinociceptive synergism between morphine and clonidine persists in mice made acutely or chronically tolerant to morphine. J Pharmacol Exp Ther. 1999; 288: 1107-1116.
Joshi W, Connelly NR, Reuben SS, et al.: An evaluation of the safety and efficacy of administering rofecoxib for postoperative pain management. Anesth Analg. 2003; 97: 35-38.
Reuben SS, Bhopatkar M, Maciolek H, et al.: Preemptive analgesic effect of rofecoxib after ambulatory arthroscopic knee surgery. Anesth Analg. 2002; 94: 55-59.
Malmberg AB, Yaksh TL: Hyperalgesia mediated by spinal glutamate or substance P receptor blocked by spinal cyclooxygenase inhibition. Science. 1992; 257: 1276-1279.
Malmberg AB, Yaksh TL: Cyclooxygenase inhibition and the spinal release of prostaglandin E2 and amino acids evoked by paw formalin injection: A Microdialysis study in unanesthetized rats. J Neurosci. 1995; 15: 2768-2776.
Tröster A, Sittl R, Singler B, et al.: Modulation of remifentanil- induced analgesia and postinfusion hyperalgesia by parecoxib in humans. Anesthesiology. 2006; 105: 1016-1023.
Lee SC, Wang JJ, Ho ST: Nalbuphine coadministered with morphine prevents tolerance and dependence. Anesth Analg. 1997; 84: 810-815.
Tao PL, Hwang CL, Chen CY: U-50,488 blocks the development of morphine tolerance and dependence at very low dose in mice. Eur J Pharmacol. 1994; 256: 281-286.
Koppert W, Ihmsen H, Koerber N, et al.: Different profiles of buprenorphine-induced analgesia and antihyperalgesia in a human pain model. Pain. 2005; 118: 15-22.
Sittl R. Transdermal buprenorphine in the treatment of chronic pain. Expert Rev Neurother. 2005; 5:315-323.
Simmonet G: Opioids: From analgesia to anti-hyperalgesia? Pain. 2005; 118: 8-9.
Bruera E, Peirera J, Watanabe C, et al.: Opioid rotation in patients with cancer pain. A retrospective comparison of dose ratios between methadone, hydromorphone, and morphine. Cancer. 1996; 78: 852-857.
Mercadante S. Opioid rotation for cancer pain: Rationale and clinical aspects. Cancer. 1999; 86: 1856-1866.
Thomsen AB, Becker N, Eriksen J: Opioid rotation in chronic non-malignant pain patients. Acta Anaesthesiol Scand. 1999; 43: 918-923.
Morley JS, Watt JW, Wells JC, et al.: Methadone in pain uncontrolled by morphine. Lancet. 1993; 342: 1243.
Williams PI, Sarginson RE, Ratcliffe JM: Use of methadone in the morphine-tolerant burned paediatric patient. Br J Anaesth. 1998; 80: 92-95.
Pocock N: Case report and discussion: Opioid-induced hyperalgesia. J Clin Oncol. 2007; 25: 4497-4498.
Siniscalchi A, Piraccini E, Miklosova Z, et al.: Opioidinduced hyperalgesia and rapid opioid detoxification after tacrolimus administration. Anesth Analg. 2008; 106: 645-646.
Zylicz Z, Krajnik M: Opioid-induced hyperalgesia as a problem in pain management. Mechanisms of onset, diagnosis and treatment. Adv Palliat Med. 2007; 6: 37-44.
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