Illness-induced hyperalgesia is mediated by spinal neuropeptides and excitatory amino acids

Brain Res. 1994 Nov 21;664(1-2):17-24. doi: 10.1016/0006-8993(94)91948-8.

Abstract

The spinal cord dorsal horn contains neural mechanisms which can greatly facilitate pain. We have recently shown that 'illness'-inducing agents, such as intraperitoneally administered lipopolysaccharide (LPS; bacterial endotoxin), can produce prolonged hyperalgesia. This hyperalgesic state is mediated at the level of the spinal cord via activation of the NMDA-nitric oxide cascade. However, prolonged neuronal depolarization is required before such a cascade can occur. The present series of experiments were aimed at identifying spinal neurotransmitters which might be responsible for creating such a depolarized state. These studies show that LPS hyperalgesia is mediated at the level of the spinal cord by substance P, cholecystokinin and excitatory amino acids acting at non-NMDA sites. No apparent role for serotonin or kappa opiate receptors was found.

Publication types

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

MeSH terms

  • 6-Cyano-7-nitroquinoxaline-2,3-dione / pharmacology
  • Animals
  • Biphenyl Compounds / pharmacology
  • Cholecystokinin / antagonists & inhibitors
  • Cholecystokinin / pharmacology
  • Disease
  • Excitatory Amino Acids / physiology*
  • Hyperalgesia / etiology*
  • Hyperalgesia / physiopathology
  • Hyperalgesia / prevention & control
  • Injections, Spinal
  • Lipopolysaccharides / antagonists & inhibitors
  • Neuropeptides / physiology*
  • Rats
  • Rats, Sprague-Dawley
  • Receptors, Opioid, kappa / antagonists & inhibitors
  • Serotonin / pharmacology
  • Spinal Cord / chemistry*
  • Substance P / antagonists & inhibitors

Substances

  • Biphenyl Compounds
  • Excitatory Amino Acids
  • Lipopolysaccharides
  • Neuropeptides
  • Receptors, Opioid, kappa
  • Serotonin
  • Substance P
  • 6-Cyano-7-nitroquinoxaline-2,3-dione
  • Cholecystokinin
  • CP 96345