Enhancement of dynorphin gene expression in spinal cord following experimental inflammation: stimulus specificity, behavioral parameters and opioid receptor binding.
The stimulus specificity for enhancement of dynorphin gene expression in rat spinal cord was studied by combined measurements of the peptide dynorphin A 1-8 and preprodynorphin mRNA levels during peripheral inflammation induced by several agents. The density of kappa receptors, the putative receptor for dynorphin peptides, was examined using receptor binding with autoradiographic visualization. Mu and delta receptor classes were also studied. All inflammatory agents tested (carrageenan, phorbol ester, yeast and Freund's adjuvant) rapidly induced edema and thermal hyperalgesia. All agents also induced a rapid (within 8 h) elevation in dynorphin mRNA and, in comparison, a delayed (within 2 days) elevation of dynorphin A 1-8 peptide; peak peptide levels were reached at 4 days. No alteration of kappa, mu or delta receptor binding was observed at 4 h or 4 days post inflammation. The rapid development of thermal hyperalgesia and elevation of dynorphin mRNA and peptide content indicates that the involvement of dynorphin-containing neurons in nociceptive processing does not require a chronic abnormality and a dynamic picture of opioid modulation of sensory processing emerges. These data also demonstrate that activation of dynorphin biosynthesis in spinal cord is a feature common to hyperalgesia and peripheral inflammation and is not restricted to any one type of inflammatory agent. The lack of alteration in receptors suggests that the physiological effects of an increased biosynthesis are not accompanied by a concurrent down-regulation of opiate receptors.
Iadarola
Michael J
MJ
Neurobiology and Anesthesiology Branch, National Institute of Dental Research, Bethesda, MD 20892 U.S.A. Unit on Functional Neuroanatomy, National Institute of Mental Health, Bethesda, MD 20892 U.S.A.
Brady
Linda S
LS
Draisci
Gaetano
G
Dubner
Ronald
R
D000818:Animals; D001522:Behavior, Animal / Q000502:physiology*; D001835:Body Weight; D004399:Dynorphins / Q000378:metabolism*; D004723:Endorphins / Q000378:metabolism; D005786:Gene Expression Regulation; D006358:Hot Temperature; D006930:Hyperalgesia / Q000378:metabolism / Q000503:physiopathology; D007249:Inflammation / Q000378:metabolism*; D008297:Male; D010446:Peptide Fragments / Q000378:metabolism*; D011498:Protein Precursors / Q000378:metabolism*; D051381:Rats; D011919:Rats, Inbred Strains; D011957:Receptors, Opioid / Q000378:metabolism*; D013116:Spinal Cord / Q000378:metabolism* / Q000503:physiopathology
D004723:Endorphins; D010446:Peptide Fragments; D011498:Protein Precursors; D011957:Receptors, Opioid; C036448:pre-prodynorphin; D004399:Dynorphins; C026770:dynorphin (1-8)