Opioid peptides (DAGO-enkephalin, dynorphin A(1-13), BAM 22P) microinjected into the rat brainstem: comparison of their antinociceptive effect and their effect on neuronal firing in the rostral ventromedial medulla.
The highly mu-selective agonist Tyr-D-Ala-Gly-MePhe-Gly-ol-enkephalin (DAGO) produces potent, dose-dependent naloxone-reversible antinociception when microinjected into the ventrolateral periaqueductal gray (PAG) (ED50 = 0.72 nmol) or rostral ventromedial medulla (RVM) (ED50 = 0.05 nmol) as measured on the rat tail flick (TF) assay. In single-unit recording experiments, DAGO microinjected into the PAG also affected On- and Off-Cell firing in the RVM in the same way as previously demonstrated by our group for morphine. PAG-microinjected DAGO inhibits spontaneous and noxious-evoked On-Cell firing (attenuating the characteristic On-Cell burst) (n = 19), and excites spontaneous Off-Cell firing, preventing the characteristic Off-Cell pause (n = 12) at doses which suppress the TF. These results support a major role for the mu receptor in PAG and RVM mechanisms of opiate antinociception. In our experiments using BAM22P, an endogenous weakly mu-selective opioid peptide, we could not demonstrate a dose-dependent antinociceptive effect, whether the peptide was microinjected supraspinally into the PAG (n = 9) or RVM (n = 11), or intrathecally at the lumbar cord (n = 4). In two animals, a naloxone-reversible antinociceptive effect was observed following the microinjection of 10 nmol BAM 22P into the RVM; however, no effect was seen in 3 animals microinjected with 20 nmol. Dyn A(1-13), a putative endogenous ligand for the kappa receptor, had no antinociceptive effect when microinjected into the ventrolateral PAG, and no effect on the firing (spontaneous or noxious-evoked) of RVM On (n = 3)- or Off (n = 2)-Cells.
Fang
F G
FG
Department of Neurology, University of California, San Francisco 94143.
Haws
C M
CM
Drasner
K
K
Williamson
A
A
Fields
H L
HL
D000200:Action Potentials / Q000187:drug effects; D000700:Analgesics / Q000494:pharmacology*; D000818:Animals; D004305:Dose-Response Relationship, Drug; D004399:Dynorphins / Q000494:pharmacology*; D020875:Enkephalin, Ala(2)-MePhe(4)-Gly(5)-; D004744:Enkephalin, Methionine / Q000031:analogs & derivatives* / Q000494:pharmacology; D004745:Enkephalins / Q000494:pharmacology*; D008297:Male; D008526:Medulla Oblongata / Q000187:drug effects / Q000502:physiology*; D010446:Peptide Fragments / Q000494:pharmacology*; D010487:Periaqueductal Gray / Q000187:drug effects / Q000502:physiology*; D011498:Protein Precursors / Q000494:pharmacology*; D051381:Rats; D011919:Rats, Inbred Strains; D011957:Receptors, Opioid / Q000502:physiology*; D017450:Receptors, Opioid, mu
D000700:Analgesics; D004745:Enkephalins; D010446:Peptide Fragments; D011498:Protein Precursors; D011957:Receptors, Opioid; D017450:Receptors, Opioid, mu; D020875:Enkephalin, Ala(2)-MePhe(4)-Gly(5)-; D004744:Enkephalin, Methionine; C026843:dynorphin (1-13); D004399:Dynorphins; C028837:BAM 22P