Preclinical study in a postoperative pain model to investigate the action of ketamine, lidocaine, and ascorbic acid in reversing fentanyl-induced, non–glutamate-dependent hyperalgesia

Abstract. Introduction:. Opioid-induced hyperalgesia (OIH) is a paradoxical phenomenon in which exposure to opioids can increase sensitivity to painful stimuli. Currently, several drugs have been used in an attempt to prevent OIH. We design this study to address the effect of preemptive treatment wi...

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Bibliographic Details
Main Authors: Marina Ayres Delgado, Luana Assis Ferreira, Bianka Jaciara dos Santos Gomes, Isis Katarine Orlandi Leite, Marcus Vinícius Gomez, Célio Castro-Junior
Format: Article
Language:English
Published: Wolters Kluwer 2023-04-01
Series:PAIN Reports
Online Access:http://journals.lww.com/painrpts/fulltext/10.1097/PR9.0000000000001062
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Summary:Abstract. Introduction:. Opioid-induced hyperalgesia (OIH) is a paradoxical phenomenon in which exposure to opioids can increase sensitivity to painful stimuli. Currently, several drugs have been used in an attempt to prevent OIH. We design this study to address the effect of preemptive treatment with ketamine, lidocaine, and ascorbic acid in a rat preclinical model of perioperative opioid-induced hyperalgesia. Methods:. To reproduce OIH in a model of postoperative pain, rats received successive doses of fentanyl subcutaneously and underwent an incision in the paw. In an attempt to prevent OIH, ketamine, lidocaine, and ascorbic acid were administered before treatment with fentanyl. The von Frey test and the hot-plate test were used to evaluate mechanical allodynia and thermal hyperalgesia, respectively, with a follow-up period from 1 hour up to 7 days after surgery. Spinal cord nerve terminals (synaptosomes) were used to assess glutamate release under our experimental conditions. Results:. Consecutive fentanyl injections increased the postoperative pain as indicated by increased thermal hyperalgesia and allodynia 48 hours after incision. Ketamine, lidocaine, and the combination of ketamine + lidocaine were able to prevent thermal hyperalgesia but not mechanical allodynia. Ascorbic acid did not prevent the hyperalgesia induced by fentanyl. We found no correlation between spinal glutamate release and the pharmacological treatments. Conclusion:. Fentanyl induced a hyperalgesic effect that last few days in a postoperative model of pain. Hyperalgesic effect was not totally inhibited by ketamine and lidocaine in rats. Increased glutamate release was not the main molecular mechanism of fentanyl-induced hyperalgesia.
ISSN:2471-2531