biostudies-literatureUnknown47(2)Laboureyras EUniversity Bordeaux, University Pierre et Marie Curie, University Paris Descartes, French CNRS, INSERM, Conseil Regional Aquitaine, Ministère enseignement Supérieur recherche et InnovationUniv Bordeaux French CNRS INSERM Univ Pierre et Marie Curie Univ Paris Descartes Conseil Regional Aquitaine Ministère Enseignement Superieur Recherche et InnovationOpioids are a mainstay of pain management but can induce unwanted effects, including analgesic tolerance and paradoxical hyperalgesia, either of which leads to increased pain. Clinically, however, the relationship between these two phenomena remains elusive. By evaluating changes in mechanical nociceptive threshold in male rats, we found that in contrast to a purely analgesic control response to a single subcutaneous administration of fentanyl (25 μg/kg), in rats subjected to inflammatory pain 2 weeks previously (Day₀), the same test dose (D₁₃) induced a bi-phasic response: initial decreased analgesia (tolerance) followed by hyperalgesia lasting several hours. Both the tolerance and hyperalgesia were further enhanced in rats that had additionally received fentanyl on Neuropsychopharmacology : official publication of the American College of Neuropsychopharmacology599-608https://www.ebi.ac.uk/biostudies/studies/S-EPMC8674360biostudies-literatureFentanyl-induced hyperalgesia and analgesic tolerance in male rats: common underlying mechanisms and prevention by a polyamine deficient diet.PMC8674360Pohl MBoujema MBMauborgne ASimonnet GLaboureyras ESimmers JfalseFentanyl-induced hyperalgesia and analgesic tolerance in male rats: common underlying mechanisms and prevention by a polyamine deficient diet.Opioids are a mainstay of pain management but can induce unwanted effects, including analgesic tolerance and paradoxical hyperalgesia, either of which leads to increased pain. Clinically, however, the relationship between these two phenomena remains elusive. By evaluating changes in mechanical nociceptive threshold in male rats, we found that in contrast to a purely analgesic control response to a single subcutaneous administration of fentanyl (25 μg/kg), in rats subjected to inflammatory pain 2 weeks previously (Day₀), the same test dose (D₁₃) induced a bi-phasic response: initial decreased analgesia (tolerance) followed by hyperalgesia lasting several hours. Both the tolerance and hyperalgesia were further enhanced in rats that had additionally received fentanyl on 2022-01-01T00:00:00Z2022 Jan2025-04-26T00:27:43.248Z2025-02-19T03:30:44.869ZS-EPMC86743603462101610.1038/s41386-021-01200-5