Cellular basis for opioid potentiation in the rostral ventromedial medulla of rats with persistent inflammatory nociception

Pain. 2010 Apr;149(1):107-116. doi: 10.1016/j.pain.2010.01.017. Epub 2010 Feb 20.

Abstract

Direct inhibition of pain facilitatory neurons in the rostral ventromedial medulla (RVM) is one mechanism by which mu opioid receptor (MOPr) agonists are proposed to produce antinociception. The antinociceptive and anti-hyperalgesic effects of the MOPr agonist DAMGO are enhanced after intraplantar injection of complete Freund's adjuvant (CFA). This study therefore examined whether CFA treatment similarly enhanced the ability of DAMGO to induce outward currents in spinally projecting RVM neurons. It further examined whether the electrophysiological properties of RVM neurons are altered by CFA treatment. Whole-cell patch clamp recordings were made from three types of serotonergic as well as non-serotonergic spinally projecting RVM neurons obtained from control rats and rats 4h or four days after CFA. Persistent, but not acute inflammatory nociception increased the percentage of Type 2 non-serotonergic neurons that responded to DAMGO from 17% to 57% and the percentage of Type 3 serotonergic neurons that responded to DAMGO from 5% to 55%. These same two populations of RVM neurons exhibited significant differences in their passive membrane properties or spontaneous discharge rate. The outward currents produced by the GABA(B) receptor agonist baclofen were not enhanced, suggesting that the enhancement does not reflect global changes in levels of G(i/o) or activity of G-protein regulated inwardly rectifying potassium channels. These results provide a cellular basis for the enhanced anti-hyperalgesic and antinociceptive effects of MOPr agonists under conditions of persistent inflammatory nociception. These results also provide intriguing, albeit indirect, evidence for two different populations of pain facilitatory neurons in the RVM.

Publication types

  • Research Support, N.I.H., Extramural

MeSH terms

  • Analgesics, Opioid / administration & dosage*
  • Animals
  • Chronic Disease
  • Drug Synergism
  • Hyperalgesia / physiopathology*
  • Hyperalgesia / prevention & control*
  • Male
  • Medulla Oblongata / drug effects
  • Medulla Oblongata / physiopathology*
  • Rats
  • Rats, Sprague-Dawley
  • Receptors, Opioid, mu / metabolism*

Substances

  • Analgesics, Opioid
  • Receptors, Opioid, mu