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

Neuroscience. 2007 Jan 5;144(1):247-62. doi: 10.1016/j.neuroscience.2006.08.078. Epub 2006 Oct 19.

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.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Aging / psychology*
  • Analgesics, Opioid / administration & dosage
  • Analgesics, Opioid / adverse effects*
  • Analgesics, Opioid / pharmacology*
  • Animals
  • Animals, Newborn
  • Behavior, Animal / drug effects
  • Drug Implants
  • Drug Tolerance
  • Female
  • Hot Temperature
  • Hyperalgesia / chemically induced
  • Hyperalgesia / psychology
  • Infusion Pumps, Implantable
  • Injections, Subcutaneous
  • Male
  • Morphine / administration & dosage
  • Morphine / adverse effects*
  • Morphine / pharmacology*
  • Pain / chemically induced*
  • Pain / etiology*
  • Pain Measurement / drug effects
  • Pain Threshold / drug effects
  • Physical Stimulation
  • Rats
  • Rats, Sprague-Dawley
  • Reaction Time / drug effects
  • Substance Withdrawal Syndrome / psychology*
  • Weight Gain / drug effects

Substances

  • Analgesics, Opioid
  • Drug Implants
  • Morphine