Mu and delta opioid synergy between the periaqueductal gray and the rostro-ventral medulla

Brain Res. 1994 Nov 28;665(1):85-93. doi: 10.1016/0006-8993(94)91155-x.


Microinjection of [D-Ala2,MePhe4,Gly(ol)5]enkephalin (DAMGO) into either the periaqueductal gray (PAG) or the rostral ventral medulla (RVM) elicits analgesia in the tailflick assay in the rat. Co-administration of DAMGO into both regions together results in a profound synergistic interaction similar to that we previously reported with morphine. U50,488H and DPDPE are inactive when given into either region. [D-Ala2,Glu4]Deltorphin (deltorphin), on the other hand, elicits an analgesic response, although the maximal response is less than than mu agonists. Co-administration of DAMGO into one region with deltorphin in the other also results in a significant synergy. However, co-administration of DAMGO and deltorphin together in the same region gives only additive effects. These results confirm the existence of mu/mu synergy between the PAG and RVM. kappa 1 and delta 1 agents are inactive, but the delta 2 agonist deltorphin is active in both regions. Our results indicate the presence of mu/delta 2 synergy between the PAG and RVM which appears to involve interactions of pathways rather than receptor interactions at the cellular level.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • 3,4-Dichloro-N-methyl-N-(2-(1-pyrrolidinyl)-cyclohexyl)-benzeneacetamide, (trans)-Isomer
  • Amino Acid Sequence
  • Analgesics / pharmacology
  • Animals
  • Drug Synergism
  • Enkephalin, Ala(2)-MePhe(4)-Gly(5)-
  • Enkephalin, D-Penicillamine (2,5)-
  • Enkephalins / pharmacology
  • Male
  • Medulla Oblongata / drug effects
  • Medulla Oblongata / physiology*
  • Molecular Sequence Data
  • Oligopeptides / pharmacology
  • Pain / physiopathology*
  • Periaqueductal Gray / drug effects
  • Periaqueductal Gray / physiology*
  • Pyrrolidines / pharmacology
  • Rats
  • Rats, Sprague-Dawley
  • Receptors, Opioid, delta / drug effects
  • Receptors, Opioid, delta / physiology*
  • Receptors, Opioid, mu / drug effects
  • Receptors, Opioid, mu / physiology*


  • Analgesics
  • Enkephalins
  • Oligopeptides
  • Pyrrolidines
  • Receptors, Opioid, delta
  • Receptors, Opioid, mu
  • Enkephalin, Ala(2)-MePhe(4)-Gly(5)-
  • deltorphin
  • 3,4-Dichloro-N-methyl-N-(2-(1-pyrrolidinyl)-cyclohexyl)-benzeneacetamide, (trans)-Isomer
  • Enkephalin, D-Penicillamine (2,5)-