Tolerance, opioid-induced allodynia and withdrawal associated allodynia in infant and young rats

• Published in: Neuroscience 2007-01, Vol.144 (1), p.247-262
• Main Authors: Zissen, M.H, Zhang, G, McKelvy, A, Propst, J.T, Kendig, J.J, Sweitzer, S.M
• Format: Article
• Language: English
• Subjects: Aging - psychology; allodynia; Analgesics, Opioid - administration & dosage; Analgesics, Opioid - adverse effects; Analgesics, Opioid - pharmacology; Animals; Animals, Newborn; Behavior, Animal - drug effects; Biological and medical sciences; Drug Implants; Drug Tolerance; Female; Fundamental and applied biological sciences. Psychology; Hot Temperature; hyperalgesia; Hyperalgesia - chemically induced; Hyperalgesia - psychology; Infusion Pumps, Implantable; Injections, Subcutaneous; Male; Medical sciences; Morphine - administration & dosage; Morphine - adverse effects; Morphine - pharmacology; morphine withdrawal; neonatal rat; Nervous system (semeiology, syndromes); Nervous system as a whole; Neurology; Pain - chemically induced; Pain - etiology; Pain Measurement - drug effects; Pain Threshold - drug effects; Physical Stimulation; Rats; Rats, Sprague-Dawley; Reaction Time - drug effects; spinal cord; Substance Withdrawal Syndrome - psychology; Vertebrates: nervous system and sense organs; Weight Gain - drug effects
• ISSN: 0306-4522; 1873-7544
• DOI: 10.1016/j.neuroscience.2006.08.078

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.