Illness-induced hyperalgesia is mediated by a spinal NMDA-nitric oxide cascade.
A variety of experimental manipulations produce enhanced pain responsivity. Recent work has demonstrated that activation of N-methyl-D-aspartate (NMDA) receptors in the spinal cord can produce persistent enhancement of pain via production of nitric oxide and/or prostaglandins. To date, the behavioral paradigms used to study NMDA mediated hyperalgesia have all involved direct excitation of spinal cord dorsal horn neurons via activation of primary nociceptive afferents. The present series of experiments examined whether the NMDA cascade would also be activated by events that do not produce direct pain input to the spinal cord dorsal horn. The hyperalgesia-inducing paradigm used was intraperitoneal lipopolysaccharide (LPS), which causes transient illness. Prior work has shown that LPS induces hyperalgesia via activation of hepatic vagal afferents to the brain, thereby activating a centrifugal pain facilitory circuit. The present study demonstrates that this centrifugal hyperalgesia is produced via activation of the NMDA-nitric oxide cascade at the level of the spinal cord.
Wiertelak
E P
EP
Department of Psychology, Macalester College, St. Paul, MN.
Furness
L E
LE
Watkins
L R
LR
Maier
S F
SF
D015763:2-Amino-5-phosphonovalerate / Q000494:pharmacology; D000818:Animals; D001120:Arginine / Q000031:analogs & derivatives / Q000494:pharmacology; D001241:Aspirin / Q000494:pharmacology; D001667:Binding, Competitive; D004194:Disease; D016291:Dizocilpine Maleate / Q000494:pharmacology; D006930:Hyperalgesia / Q000209:etiology* / Q000503:physiopathology; D007278:Injections, Spinal; D008070:Lipopolysaccharides / Q000494:pharmacology; D019331:NG-Nitroarginine Methyl Ester; D009569:Nitric Oxide / Q000037:antagonists & inhibitors / Q000502:physiology*; D011453:Prostaglandins / Q000502:physiology*; D051381:Rats; D017207:Rats, Sprague-Dawley; D016194:Receptors, N-Methyl-D-Aspartate / Q000187:drug effects / Q000502:physiology*; D013116:Spinal Cord / Q000187:drug effects / Q000503:physiopathology*
D008070:Lipopolysaccharides; D011453:Prostaglandins; D016194:Receptors, N-Methyl-D-Aspartate; D009569:Nitric Oxide; D016291:Dizocilpine Maleate; D015763:2-Amino-5-phosphonovalerate; D001120:Arginine; D001241:Aspirin; D019331:NG-Nitroarginine Methyl Ester