Fentanyl-induced hyperalgesia and analgesic tolerance in male rats: common underlying mechanisms and prevention by a polyamine deficient diet

Autor: Annie Mauborgne, Guy Simonnet, Meric Ben Boujema, Michel Pohl, John Simmers, Emilie Laboureyras
Jazyk: angličtina
Rok vydání: 2021
Předmět:
Zdroj: Neuropsychopharmacology
Popis: 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 (Day(0)), the same test dose (D(13)) 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 D(0). The dose-response profiles (5 fg to 50 μg/kg) of pain- and opioid-experienced rats were very different from pain/drug-naive rats. At ultra-low fentanyl doses (
Databáze: OpenAIRE