RGS9-2 modulates nociceptive behaviour and opioid-mediated synaptic transmission in the spinal dorsal horn

Neurosci Lett. 2011 Aug 21;501(1):31-4. doi: 10.1016/j.neulet.2011.06.033. Epub 2011 Jun 29.


The regulator of G protein signaling 9-2 (RGS9-2) is a constituent of G protein-coupled receptor (GPCR) macromolecular complexes with a major role in regulation of GPCR activity in the central nervous system. Previous in situ hybridization and Western blot studies revealed that RGS9-2 is expressed in the superficial dorsal horn of the spinal cord. In the present study, we monitored tail withdrawal latencies to noxious thermal stimuli and performed in vitro whole-cell patch clamp electrophysiological recordings from neurons in lamina II of the spinal dorsal horn to examine the role of RGS9-2 in the dorsal horn of the spinal cord in nociceptive behaviours and opiate mediated modulation of synaptic transmission. Our findings obtained from RGS9 knockout mice indicate that the lack of RGS9-2 protein decreases sensitivity to thermal stimuli and to the analgesic actions of morphine in the tail immersion paradigm. This modulatory role of RGS9-2 on opiate-mediated responses was further supported by electrophysiological studies showing that hyperpolarization of neurons in lamina II of the spinal dorsal horn evoked by application of DAMGO ([d-Ala2, N-MePhe4, Gly-ol]-enkephalin, a mu opioid receptor agonist) was diminished in RGS9 knockout mice. The results indicate that RGS9-2 enhances the effect of morphine and may play a crucial role in opiate-mediated analgesic mechanisms at the level of the spinal cord.

MeSH terms

  • Analgesics, Opioid / pharmacology
  • Animals
  • Behavior, Animal / drug effects
  • Behavior, Animal / physiology*
  • Enkephalin, Ala(2)-MePhe(4)-Gly(5)- / pharmacology
  • Male
  • Mice
  • Mice, Knockout
  • Morphine / pharmacology
  • Pain / metabolism*
  • Pain / physiopathology
  • Posterior Horn Cells / drug effects
  • Posterior Horn Cells / metabolism*
  • RGS Proteins / genetics
  • RGS Proteins / metabolism*
  • Receptors, Opioid, mu / metabolism*
  • Spinal Cord / drug effects
  • Spinal Cord / metabolism
  • Spinal Cord / physiopathology
  • Synaptic Transmission / drug effects
  • Synaptic Transmission / physiology*


  • Analgesics, Opioid
  • RGS Proteins
  • Receptors, Opioid, mu
  • regulator of g-protein signaling 9
  • Enkephalin, Ala(2)-MePhe(4)-Gly(5)-
  • Morphine