AMPAkines and morphine provide complementary analgesia

Behav Brain Res. 2017 Sep 15:334:1-5. doi: 10.1016/j.bbr.2017.07.020. Epub 2017 Jul 19.

Abstract

Glutamate signaling in the central nervous system is known to play a key role in pain regulation. AMPAkines can enhance glutamate signaling through α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA) receptors. previous studies have shown that AMPAkines are effective analgesic agents, and their site of action is likely in the brain. It is not known, however, if AMPAkines can provide complementary analgesia in combination with opioids, the most commonly used analgesics. Here, we show that the co-administration of an AMPAkine with morphine can provide additional analgesia, both in naïve rats and in rats that experience postoperative pain. Furthermore, we show that this AMPAkine can be administered directly into the prefrontal cortex to provide analgesia, and that prefrontal AMPAkine infusion, similar to systemic administration, can provide added pain relief to complement morphine analgesia.

Keywords: AMPAkines; Analgesia; Morphine; Prefrontal cortex.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Analgesia / methods
  • Analgesics, Non-Narcotic / administration & dosage*
  • Analgesics, Opioid / pharmacology*
  • Animals
  • Dioxoles / administration & dosage*
  • Disease Models, Animal
  • Dose-Response Relationship, Drug
  • Drug Synergism
  • Excitatory Amino Acid Agents / administration & dosage*
  • Glutamic Acid / metabolism
  • Hot Temperature
  • Male
  • Morphine / pharmacology*
  • Pain Threshold / drug effects
  • Pain, Postoperative / drug therapy
  • Piperidines / administration & dosage*
  • Prefrontal Cortex / drug effects*
  • Prefrontal Cortex / metabolism
  • Rats, Sprague-Dawley
  • Receptors, AMPA / metabolism

Substances

  • 1-(1,4-benzodioxan-6-ylcarbonyl)piperidine
  • Analgesics, Non-Narcotic
  • Analgesics, Opioid
  • Dioxoles
  • Excitatory Amino Acid Agents
  • Piperidines
  • Receptors, AMPA
  • Glutamic Acid
  • Morphine