Acute and late effects on induction of allodynia by acromelic acid, a mushroom poison related structurally to kainic acid

Abstract

1. Ingestion of a poisonous mushroom Clitocybe acromelalga is known to cause severe tactile pain (allodynia) in the extremities for a month and acromelic acid (ACRO), a kainate analogue isolated from the mushroom, produces selective damage of interneurons of the rat lower spinal cord when injected either systemically or intrathecally. Since ACRO has two isomers, ACRO-A and ACRO-B, here we examined their acute and late effects on induction of allodynia. 2. Intrathecal administration of ACRO-A and ACRO-B provoked marked allodynia by the first stimulus 5 min after injection, which lasted over the 50-min experimental period. Dose-dependency of the acute effect of ACRO-A on induction of allodynia showed a bell-shaped pattern from 50 ag kg -1 to 0.5 pg kg -1 and the maximum effect was observed at 50 fg kg -1. On the other hand, ACRO-B induced allodynia in a dose-dependent manner from 50 pg kg -1 to 50 ng kg -1. 3. N-methyl-D-aspartate (NMDA) receptor antagonists and Joro spider toxin, a Ca 2+-permeable AMPA receptor antagonist, inhibited the allodynia induced by ACRO-A, but not by ACRO-B. However, other AMPA/kainate antagonists did not affect the allodynia induced by ACRO. 4. Whereas no neuronal damage was observed in the spinal cord in ACRO-A-treated mice, induction of allodynia by ACRO-A (50 fg kg -1) and ACRO-B (50 ng kg -1) was selectively lost 1 week after i.t. injection of a sublethal dose of ACRO-A (50 ng kg -1) or ACRO-B (250 ng kg -1). Higher doses of ACRO-A, however, could evoke allodynia dose-dependently from 50 pg kg -1 to 500 ng kg -1 in the ACRO-A-treated mice. The allodynia induced by ACRO-A (500 ng kg -1) was not inhibited by Joro spider toxin or NMDA receptor antagonists. These properties of the late allodynia induced by ACRO-A were quite similar to those of the acute allodynia induced by ACRO-B. 5. ACRO-A could increase [Ca 2+] i in the deeper laminae, rather than in the superficial laminae, of the spinal cord. This increase was not blocked by the AMPA-preferring antagonist GYKI52466 and Joro spider toxin. 6. Taken together, these results demonstrate the stereospecificity of ACRO for the induction of allodynia and suggest the presence of a receptor specific to ACRO.