Induction of c-Fos and zif268 in the nociceptive amygdala parallel abstinence hyperalgesia in rats briefly exposed to morphine.
Opioid-induced analgesia can be followed by spontaneous pain in humans, and hyperalgesia in rodents. In this study, opioid-induced hyperalgesia was measured by the tail-flick test when acute abstinence was precipitated by administering naloxone to drug naive rats that had experienced morphine analgesia for only 30 min. In a further experiment, the drug treatment that previously caused opioid-induced hyperalgesia was found to increase neurons expressing nuclear c-Fos or zif268 proteins in extended amygdalar regions targeted by projections of the ascending spino-parabrachio-amygdaloid nociceptive pathway. Transcription factor induction, however, was not detected in multiple brain regions known to respond in parallel with the same extended amygdalar structures when (1) rats are exposed to interoceptive/physical stressors, or (2) naloxone is used to precipitate abstinence in opioid dependent rats. Surprisingly, in many regions c-Fos induction by morphine was reduced or blocked by naloxone, even though these subjects had also experienced the effects of morphine for 30 min prior to antagonist administration. It is suggested transcription factor induction during opioid hyperalgesia in non-dependent rats could support the induction or consolidation of neural plasticity in nociceptive amygdaloid circuitry previously suggested to function in bi-directional control of pain and expression of pain-related behaviors.
Hamlin
Adam S
AS
Pain Management Research Institute (Kolling Institute), The University of Sydney at the Royal North Shore Hospital, St Leonards, NSW 2065, Australia.
McNally
Gavan P
GP
Osborne
Peregrine B
PB
D000679:Amygdala / Q000187:drug effects / Q000378:metabolism*; D000818:Animals; D001522:Behavior, Animal / Q000187:drug effects; D015740:Calcitonin Gene-Related Peptide / Q000378:metabolism; D002452:Cell Count; D004305:Dose-Response Relationship, Drug; D004334:Drug Administration Schedule; D004347:Drug Interactions; D051766:Early Growth Response Protein 1 / Q000378:metabolism*; D018565:Food-Drug Interactions / Q000528:radiation effects; D006930:Hyperalgesia / Q000139:chemically induced / Q000378:metabolism*; D008297:Male; D009020:Morphine / Q000008:administration & dosage*; D009270:Naloxone; D009294:Narcotics / Q000008:administration & dosage*; D010147:Pain Measurement; D016760:Proto-Oncogene Proteins c-fos / Q000378:metabolism*; D051381:Rats; D017208:Rats, Wistar; D011930:Reaction Time / Q000187:drug effects; D014446:Tyrosine 3-Monooxygenase / Q000378:metabolism
D051766:Early Growth Response Protein 1; C486110:Egr1 protein, rat; D009294:Narcotics; D016760:Proto-Oncogene Proteins c-fos; D009270:Naloxone; D009020:Morphine; D014446:Tyrosine 3-Monooxygenase; D015740:Calcitonin Gene-Related Peptide