Differential activation of spinal cord dynorphin and enkephalin neurons during hyperalgesia: evidence using cDNA hybridization.
A unilateral experimental inflammation of the hindlimb produces hyperalgesia to both mechanical and radiant thermal stimuli that is rapid in onset. During this period, parameters of dynorphin biosynthesis are elevated to a much greater degree than those of the enkephalin system. An increase in the content of the peptide dynorphin A(1-8) occurs in the spinal cord segments that receive sensory input from the affected limb. This is accompanied by a rapid (within 24 h) and pronounced increase in the levels of mRNA coding for the dynorphin protein precursor. Maximum elevations (6- to 8-fold) of preprodynorphin mRNA are observed between days 2 and 5 subsequent to the induction of inflammation. Compared to the increase in mRNA, the increase in dynorphin A(1-8) peptide was appreciably delayed and proportionately less; maximal increases in peptide (3-fold) were seen at day 5 of inflammation. Dorsal spinal cord preproenkephalin mRNA is elevated to a lesser degree (50-80%). However, the increase in preproenkephalin mRNA is apparently not enough to yield a measurable increase in the proenkephalin-derived peptide met5-enkephalin-Arg6-Gly7-Leu8, the levels of which showed no significant change during the 14-day inflammatory period. These data suggest the active participation of opioid neurons, especially those containing dynorphin, at the spinal level, in the modulation of sensory afferent input during peripheral inflammatory pain states.
D000818:Animals; D004247:DNA; D004399:Dynorphins / Q000378:metabolism*; D004744:Enkephalin, Methionine / Q000031:analogs & derivatives* / Q000378:metabolism; D004745:Enkephalins / Q000378:metabolism; D006930:Hyperalgesia / Q000378:metabolism*; D006941:Hyperesthesia / Q000378:metabolism*; D008297:Male; D009693:Nucleic Acid Hybridization; D010446:Peptide Fragments / Q000378:metabolism*; D011498:Protein Precursors / Q000378:metabolism; D012333:RNA, Messenger / Q000378:metabolism*; D051381:Rats; D011919:Rats, Inbred Strains
D004745:Enkephalins; D010446:Peptide Fragments; D011498:Protein Precursors; D012333:RNA, Messenger; C036448:pre-prodynorphin; D004744:Enkephalin, Methionine; D004399:Dynorphins; C026770:dynorphin (1-8); C033453:enkephalin-Met, Arg(6)-Gly(7)-Leu(8)-; D004247:DNA; C033660:preproenkephalin