Effects of prostaglandin E2 and capsaicin on behavior and cerebrospinal fluid amino acid concentrations of unanesthetized rats: a microdialysis study.
Prostaglandin E2 (PGE2) delivered to the spinal cord produces an increased sensitivity to noxious (hyperalgesia) and innocuous (allodynia) stimuli. The mechanisms that underlie this effect remain unknown, but a PGE2-evoked enhancement of spinal neurotransmitter release may be involved. To address this hypothesis, we examined the effect of PGE2 on CSF concentrations of amino acids and also the modulatory effect of PGE2 on capsaicin-evoked changes of spinal amino acid concentrations using a microdialysis probe placed in the lumbar subarachnoid space. Amino acids were quantified using HPLC with fluorescence detection. Addition of 1 mM, but not 10 or 100 microM, PGE2 to the perfusate for a 10-min period (flow rate, 5 microliters/min) evoked an immediate increase (80-100%) in glutamate (Glu), aspartate (Asp), taurine (Tau), glycine (Gly), and gamma-aminobutyric acid (GABA) concentrations. Similarly, capsaicin infusion (0.1-10 microM) induced a dose-dependent increase in Glu, Asp, Tau, Gly, GABA, and ethanolamine levels. Significant increases in amino acid levels evoked by PGE2 or capsaicin were associated with a touch-evoked allodynia. The combination of PGE2 (10 microM) and capsaicin (0.1 or 1.0 microM) at concentrations that individually had no effect together evoked a significant increase (60-100%) in Glu, Asp, Tau, Gly, and GABA concentrations and produced tactile allodynia. These data demonstrate that spinally delivered PGE2 or capsaicin substantially elevates CSF concentrations of both excitatory and inhibitory amino acids. The capacity of PGE2 to enhance and prolong capsaicin-evoked amino acid concentrations may be one of the mechanisms by which spinal PGE2 produces hyperalgesia and allodynia.
Malmberg
A B
AB
Department of Pharmacology, University of Göteborg, Sweden.
Hamberger
A
A
Hedner
T
T
D000596:Amino Acids / Q000134:cerebrospinal fluid*; D000818:Animals; D001522:Behavior, Animal / Q000187:drug effects*; D002211:Capsaicin / Q000494:pharmacology*; D015232:Dinoprostone / Q000494:pharmacology*; D008297:Male; D017551:Microdialysis; D009994:Osmolar Concentration; D051381:Rats; D017207:Rats, Sprague-Dawley
D000596:Amino Acids; D015232:Dinoprostone; D002211:Capsaicin