Treatment and measurement of neuropathic pain using acromelic acid analogues

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We previously showed that intrathecal (i.t.) administration ofacromelic acid A (Acro-A), a major causing substance of the mushroom (Clitocybeacromelalga) poison, provoked allodynia in conscious mice. To clarify a mechanism ofAcro-A, we synthesized [11C]-labeled Acro-A analogue (PSPA-4) that can competitivelyblock the Acro-A-induced allodynia. In vitro autoradiography, [C]PSPA-4 wasspecifically bound to the rat brain and spinal cord, and the binding was significantlydisplaced by kainic acid, but not by antagonists of kainate receptor. PSPA-4 attenuatedthe Acro-A-induced allodynia at low doses and induced allodynia at high doses via a bindingsite different from known kainate antagonists. The development of a radio-labeled Acro-Aanalogue will enable us to promote the understanding of the action mechanism not onlyof Acro-A, but also of pain transmission in the periphery and central nervous system.