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Effects of Prostaglandin E 2 and Capsaicin on Behavior and Cerebrospinal Fluid Amino Acid Concentrations of Unanesthetized Rats: A Microdialysis Study
Author(s) -
Malmberg Annika B.,
Hamberger Anders,
Hedner Thomas
Publication year - 1995
Publication title -
journal of neurochemistry
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.75
H-Index - 229
eISSN - 1471-4159
pISSN - 0022-3042
DOI - 10.1046/j.1471-4159.1995.65052185.x
Subject(s) - microdialysis , chemistry , capsaicin , hyperalgesia , taurine , allodynia , prostaglandin e2 , glutamate receptor , amino acid , glycine , prostaglandin e , prostaglandin , inhibitory postsynaptic potential , medicine , pharmacology , endocrinology , nociception , biochemistry , extracellular , receptor
Prostaglandin E 2 (PGE 2 ) 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 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 effect of PGE 2 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 m M , but not 10 or 100 µ M , PGE 2 to the perfusate for a 10‐min period (flow rate, 5 µl/min) evoked an immediate increase (80–100%) in glutamate (Glu), aspartate (Asp), taurine (Tau), glycine (Gly), and γ‐aminobutyric acid (GABA) concentrations. Similarly, capsaicin infusion (0.1–10 µ M ) induced a dose‐dependent increase in Glu, Asp, Tau, Gly, GABA, and ethanolamine levels. Significant increases in amino acid levels evoked by PGE 2 or capsaicin were associated with a touch‐evoked allodynia. The combination of PGE 2 (10 µ M ) and capsaicin (0.1 or 1.0 µ 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. These data demonstrate that spinally delivered PGE 2 or capsaicin substantially 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.