EFFECTS OF PROSTAGLANDIN E(2) AND CAPSAICIN ON BEHAVIOR AND CEREBROSPINAL-FLUID AMINO-ACID-CONCENTRATIONS OF UNANESTHETIZED RATS - A MICRODIALYSIS STUDY

Prostaglandin E(2) (PGE(2)) delivered to the spinal cord produces an i ncreased sensitivity to noxious (hyperalgesia) and innocuous (allodyni a) stimuli. The mechanisms that underlie this effect remain unknown, b ut a PGE(2)-evoked enhancement of spinal neurotransmitter release may be involved. To address this hypothesis, we examined the effect of PGE (2) on CSF concentrations of amino acids and also the modulatory effec t of PGE(2) on capsaicin-evoked changes of spinal amino acid concentra tions using a microdialysis probe placed in the lumbar subarachnoid sp ace. Amino acids were quantified using HPLC with fluorescence detectio n, Addition of 1 mM, but not 10 or 100 mu M, PGE(2) to the perfusate f ar a 10-min period (flow rate, 5 mu l/min) evoked an immediate increas e (80-100%) in glutamate (Glu), aspartate (Asp), taurine (Tau), glycin e (Gly), and gamma-aminobutyric acid (GABA) concentrations. Similarly, capsaicin infusion (0.1-10 mu M) induced a dose-dependent increase in Glu, Asp, Tau, Gly, GABA, and ethanolamine levels. Significant increa ses in amino acid levels evoked by PGE(2) or capsaicin were associated with a touch-evoked allodynia. The combination of PGE(2) (10 mu M) an d capsaicin (0.1 or 1.0 mu M) 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. Th ese data demonstrate that spinally delivered PGE(2) or capsaicin subst antially elevates CSF concentrations of both excitatory and inhibitory amino acids. The capacity of PGE(2) to enhance and prolong capsaicin- evoked amino acid concentrations may be one of the mechanisms by which spinal PGE(2) produces hyperalgesia and allodynia.