Illness-induced hyperalgesia is mediated by spinal neuropeptides and excitatory amino acids.
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.
Watkins
L R
LR
Department of Psychology, University of Colorado at Boulder 80309.
Wiertelak
E P
EP
Furness
L E
LE
Maier
S F
SF
D018750:6-Cyano-7-nitroquinoxaline-2,3-dione / Q000494:pharmacology; D000818:Animals; D001713:Biphenyl Compounds / Q000494:pharmacology; D002766:Cholecystokinin / Q000037:antagonists & inhibitors / Q000494:pharmacology; D004194:Disease; D018846:Excitatory Amino Acids / Q000502:physiology*; D006930:Hyperalgesia / Q000209:etiology* / Q000503:physiopathology / Q000517:prevention & control; D007278:Injections, Spinal; D008070:Lipopolysaccharides / Q000037:antagonists & inhibitors; D009479:Neuropeptides / Q000502:physiology*; D051381:Rats; D017207:Rats, Sprague-Dawley; D017473:Receptors, Opioid, kappa / Q000037:antagonists & inhibitors; D012701:Serotonin / Q000494:pharmacology; D013116:Spinal Cord / Q000737:chemistry*; D013373:Substance P / Q000037:antagonists & inhibitors
D001713:Biphenyl Compounds; D018846:Excitatory Amino Acids; D008070:Lipopolysaccharides; D009479:Neuropeptides; D017473:Receptors, Opioid, kappa; D012701:Serotonin; D013373:Substance P; D018750:6-Cyano-7-nitroquinoxaline-2,3-dione; D002766:Cholecystokinin; C066892:CP 96345