J Korean Med Assoc.  2014 Jan;57(1):41-46. 10.5124/jkma.2014.57.1.41.

Opioid-induced hyperalgesia

• Lee H

• KMID: 2194833
• DOI: http://doi.org/10.5124/jkma.2014.57.1.41

Abstract

Perioperative opioid-induced hyperalgesia (OIH) can be defined as the "increased perception of pain after opioid-based anesthesia and surgery" since hyperalgesia is defined as "increased pain from a stimulus that normally provokes pain." OIH has been identified mainly after remifentanil-based anesthesia in surgical patients given the high dose and rapid withdrawal used. The mechanisms of OIH have been postulated mainly by the cellular-level adaptation in internalization of the receptors and downregulation of intracellular coupling, upregulation of spinal dynorphins, and activation of N-methyl-D-aspartate receptors have been postulated as well. The clinical aspects of OIH with various causes, especially remifentanil, have been investigated. Pros and cons related to remifentanil-induced hyperalgesia have been suggested. The dose and duration of remifentanil used in surgery and anesthesia can be the appropriate factors for OIH, including the way of setting for the control groups of those studies, and the methods for evaluating the pain. Opioids remain one of the most powerful pain killers for acute pain management. Opioids are sometimes necessary for perioperative analgesia, but OIH can be an unavoidable risk. Ongoing interest in OIH and the development of anesthesia optimized for its prevention will increase the quality of perioperative life.

Keyword

Drug tolerance; Hyperalgesia; Opioid

MeSH Terms

Acute Pain
Analgesia
Analgesics, Opioid
Anesthesia
Down-Regulation
Drug Tolerance
Dynorphins
Humans
Hyperalgesia*
Methods
Receptors, N-Methyl-D-Aspartate
Up-Regulation
Analgesics, Opioid
Dynorphins
Receptors, N-Methyl-D-Aspartate

Reference

1. Siegel S, Hinson RE, Krank MD, McCully J. Heroin "overdose" death: contribution of drug-associated environmental cues. Science. 1982; 216:436–437.

2. Kissin I, Bright CA, Bradley EL Jr. Acute tolerance to continuously infused alfentanil: the role of cholecystokinin and N-methyl-D-aspartate-nitric oxide systems. Anesth Analg. 2000; 91:110–116.

3. Adam F, Bonnet F, Le Bars D. Tolerance to morphine analgesia: evidence for stimulus intensity as a key factor and complete reversal by a glycine site-specific NMDA antagonist. Neuropharmacology. 2006; 51:191–202.

4. Trafton JA, Abbadie C, Marek K, Basbaum AI. Postsynaptic signaling via the [mu]-opioid receptor: responses of dorsal horn neurons to exogenous opioids and noxious stimulation. J Neurosci. 2000; 20:8578–8584.

5. Gardell LR, Wang R, Burgess SE, Ossipov MH, Vanderah TW, Malan TP Jr, Lai J, Porreca F. Sustained morphine exposure induces a spinal dynorphin-dependent enhancement of excitatory transmitter release from primary afferent fibers. J Neurosci. 2002; 22:6747–6755.

6. Vinik HR, Kissin I. Rapid development of tolerance to analgesia during remifentanil infusion in humans. Anesth Analg. 1998; 86:1307–1311.

7. Gustorff B, Nahlik G, Hoerauf KH, Kress HG. The absence of acute tolerance during remifentanil infusion in volunteers. Anesth Analg. 2002; 94:1223–1228.

8. Guignard B, Bossard AE, Coste C, Sessler DI, Lebrault C, Alfonsi P, Fletcher D, Chauvin M. Acute opioid tolerance: intraoperative remifentanil increases postoperative pain and morphine requirement. Anesthesiology. 2000; 93:409–417.

9. Crawford MW, Hickey C, Zaarour C, Howard A, Naser B. Development of acute opioid tolerance during infusion of remifentanil for pediatric scoliosis surgery. Anesth Analg. 2006; 102:1662–1667.

10. Cortinez LI, Brandes V, Munoz HR, Guerrero ME, Mur M. No clinical evidence of acute opioid tolerance after remifentanil-based anaesthesia. Br J Anaesth. 2001; 87:866–869.

11. Hood DD, Curry R, Eisenach JC. Intravenous remifentanil produces withdrawal hyperalgesia in volunteers with capsaicin-induced hyperalgesia. Anesth Analg. 2003; 97:810–815.

12. Hansen EG, Duedahl TH, Romsing J, Hilsted KL, Dahl JB. Intra-operative remifentanil might influence pain levels in the immediate post-operative period after major abdominal surgery. Acta Anaesthesiol Scand. 2005; 49:1464–1470.

13. Lee LH, Irwin MG, Lui SK. Intraoperative remifentanil infusion does not increase postoperative opioid consumption compared with 70% nitrous oxide. Anesthesiology. 2005; 102:398–402.