title: Tolerance, opioid-induced allodynia and withdrawal associated allodynia in infant and young rats.
abstract: Our laboratory has previously characterized age-dependent changes in nociception upon acute morphine withdrawal. This study characterizes changes in mechanical and thermal nociception following acute, intermittent, or continuous morphine administration in infant (postnatal days 5-8) and young (postnatal days 19-21) rats. Morphine was given as a single acute administration (AM), intermittently twice a day for 3 days (IM), or continuously for 72 h via pump (CM). AM did not produce long-term changes in mechanical or thermal nociception in either infant or young rats. CM produced changes in mechanical nociception that included the development of tolerance, opioid-induced mechanical allodynia and withdrawal-associated mechanical allodynia in young rats, but only tolerance and a prolonged withdrawal-associated mechanical allodynia in infant rats. IM produced withdrawal-associated mechanical allodynia in both infant and young rats. Measuring paw withdrawal responses to thermal stimuli, infant and young rats showed tolerance without opioid-induced thermal hyperalgesia or withdrawal-associated thermal hyperalgesia following CM. In contrast to CM, withdrawal-associated thermal hyperalgesia was seen in both ages following IM. In conclusion, CM versus IM differentially modified mechanical and thermal nociception, suggesting that opioid-dependent thermal hyperalgesia and mechanical allodynia can be dissociated from each other in infant and young rats. Furthermore, tolerance, opioid-induced hypersensitivity, and withdrawal-associated hypersensitivity are age-specific and may be mediated by distinct mechanisms.
authors.affiliation: Department of Anesthesia, Stanford University School of Medicine, Stanford, CA 94305, USA.
authors.forename: M H
authors.initials: MH
authors.lastname: Zissen
authors.forename: G
authors.initials: G
authors.lastname: Zhang
authors.forename: A
authors.initials: A
authors.lastname: McKelvy
authors.forename: J T
authors.initials: JT
authors.lastname: Propst
authors.forename: J J
authors.initials: JJ
authors.lastname: Kendig
authors.forename: S M
authors.initials: SM
authors.lastname: Sweitzer
mesh_terms: D000375:Aging / Q000523:psychology*; D000701:Analgesics, Opioid / Q000008:administration & dosage / Q000009:adverse effects* / Q000494:pharmacology*; D000818:Animals; D000831:Animals, Newborn; D001522:Behavior, Animal / Q000187:drug effects; D004343:Drug Implants; D004361:Drug Tolerance; D005260:Female; D006358:Hot Temperature; D006930:Hyperalgesia / Q000139:chemically induced / Q000523:psychology; D015918:Infusion Pumps, Implantable; D007279:Injections, Subcutaneous; D008297:Male; D009020:Morphine / Q000008:administration & dosage / Q000009:adverse effects* / Q000494:pharmacology*; D010146:Pain / Q000139:chemically induced* / Q000209:etiology*; D010147:Pain Measurement / Q000187:drug effects; D017288:Pain Threshold / Q000187:drug effects; D010812:Physical Stimulation; D051381:Rats; D017207:Rats, Sprague-Dawley; D011930:Reaction Time / Q000187:drug effects; D013375:Substance Withdrawal Syndrome / Q000523:psychology*; D015430:Weight Gain / Q000187:drug effects
chemical_list: D000701:Analgesics, Opioid; D004343:Drug Implants; D009020:Morphine