The DOI matches its Crossref record; 49 of the 49 references it cites were found in a registry or an index.
Differential modulation of remifentanil-induced analgesia and postinfusion hyperalgesia by S-ketamine and clonidine in humans
Open accessAbstract
Background: Experimental studies and clinical observations suggest a possible role for opioids to induce pain and hyperalgesia on withdrawal. The authors used a new experimental pain model in human skin to determine the time course of analgesic and hyperalgesic effects of the mu-receptor agonist remifentanil alone or in combination with the N-methyl-D-aspartate-receptor antagonist S-ketamine or the alpha(2)-receptor agonist clonidine. Methods: Thirteen volunteers were enrolled in this randomized, double-blind, placebo-controlled study. Transcutaneous electrical stimulation at a high current density (2 Hz, 67.3 +/- 16.8 mA, mean +/- SD) induced acute pain (numerical 11-point rating scale: 5-6 out of 10) and stable areas of mechanical hyperalgesia to punctate stimuli and touch (allodynia). The magnitude of pain and area of hyperalgesia were assessed before, during, and after drug infusion (remifentanil at 0.1 microg x kg-1 x min-1 and S-ketamine at 5 microg x kg-1 x min-1 over a period of 30 min, respectively; clonidine infusion at 2 microg/kg for 5 min). Results: Remifentanil reduced pain and areas of punctate hyperalgesia during infusion. In contrast, postinfusion pain and hyperalgesia were significantly higher than control. During infusion of S-ketamine, pain and hyperalgesia decreased and gradually normalized after infusion. When given in combination, S-ketamine abolished postinfusion increase of punctate hyperalgesia but did not reduce increased pain ratings. Clonidine alone did not significantly attenuate pain or areas of hyperalgesia. However, when given in combination with remifentanil, clonidine attenuated postinfusion increase of pain ratings. Conclusions: Opioid-induced postinfusion hyperalgesia could be abolished by S-ketamine, suggesting an N-methyl-d-aspartate-receptor mechanism. In contrast, elevated pain ratings after infusion were not reduced by ketamine but were alleviated by the alpha(2)-receptor agonist clonidine. The results of this study suggest different mechanisms of opioid-induced postinfusion antianalgesia and secondary hyperalgesia.
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Cites
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Long-lasting Hyperalgesia Induced by Fentanyl in Rats: Preventive Effect of Ketamine
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Remifentanil Versus Alfentanil
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“Activation of the NMDA-receptor system by opioids(17,18) has been identified to account for opioidinduced hyperalgesia.(3,19,20) In fact, combining remifentanil with the NMDA-receptor antagonist ketamine has been shown to reduce postoperative opioid requirement.”
Intraoperative high dose fentanyl induces postoperative fentanyl tolerance
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Opioid-induced Hyperalgesia: A Qualitative Systematic Review
Angst, M. S., & Clark, J. D. (2006) · Anesthesiology · doi:10.1097/00000542-200603000-00025 · Cited by 1,188
Attenuation of Antidepressant Effects of Ketamine by Opioid Receptor Antagonism
Williams, N. R., Heifets, B. D., Blasey, C., Sudheimer, K., Pannu, J., Pankow, H., Hawkins, J., Birnbaum, J., Lyons, D. M., Rodriguez, C. I., et al. (2018) · American Journal of Psychiatry · doi:10.1176/appi.ajp.2018.18020138 · Cited by 519
Neurobiology of opioid addiction: Opponent process, hyperkatifeia, and negative reinforcement
Koob, G. F. (2020) · Biological Psychiatry · doi:10.1016/j.biopsych.2019.05.023 · Cited by 477
Drug Addiction: Hyperkatifeia/Negative Reinforcement as a Framework for Medications Development
Koob, G. F. (2021) · Pharmacological Reviews · doi:10.1124/pharmrev.120.000083 · Cited by 337
The impact of opioid-induced hyperalgesia for postoperative pain
Koppert, W., & Schmelz, M. (2007) · Best Practice & Research Clinical Anaesthesiology · doi:10.1016/j.bpa.2006.12.004 · Cited by 154
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Metadata
- Authors
- Koppert, W., Sittl, R., Scheuber, K., Alsheimer, M., Schmelz, M., & Schüttler, J.
- Affiliations
- Universitätsklinikum Erlangen (DE)
- Staff Anesthesiologist.
- Visiting Research Fellow.
- Heidelberg University (DE)
- Venue
- Anesthesiology
- Published
- 2003-07-01
- Volume
- 99
- Issue
- 1
- Pages
- 152-159
- ISSN
- 0003-3022 (ISSN-L)
- OpenAlex
- W2037762739
- Cited by
- 352
- References
- 49
- Citations by year
- 2026: 4 · 2025: 14 · 2024: 9 · 2023: 11 · 2022: 10 · 2021: 10 · 2020: 44 · 2019: 11 · 2018: 10 · 2017: 9 · 2016: 13 · 2015: 17 · 2014: 20 · 2013: 19 · 2012: 22
- FWCI
- 14.38
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Locations
- Anesthesiology (publishedVersion)
- PubMed (publishedVersion)
- Funders
- Deutsche Forschungsgemeinschaft
- Topics
- Health Sciences › Medicine › Anesthesiology and Pain Medicine › Anesthesia and Pain Management
- Health Sciences › Medicine › Physiology (medical) › Pain Mechanisms and Treatments
- Health Sciences › Medicine › Anesthesiology and Pain Medicine › Pain Management and Opioid Use
- Keywords
- remifentanil, opioid-induced hyperalgesia, esketamine, clonidine, NMDA receptor antagonism, secondary hyperalgesia, allodynia, mu-opioid receptor
- MeSH terms
- Remifentanil, Adrenergic alpha-Agonists, Adult, Analgesics, Opioid, Anesthetics, Dissociative, Blood Pressure, Clonidine, Double-Blind Method, Electric Stimulation, Half-Life, Humans, Hyperalgesia, Infusions, Intravenous, Ketamine, Male, Oxygen, Pain Measurement, Physical Stimulation, Piperidines, Substance Withdrawal Syndrome, Receptors, Opioid, mu, Cross-Over Studies
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