Visualization of the change in pain by the autoradiography and calcium imaging in the brain and spinal cord

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PSPA-4, an acromelic acid (Acro-A) analogue, attenuated the Acro-A-induced allodynia at low doses and induced allodynia at high doses. In vitro autoradiography, [11C]PSPA-4 was specifically bound to the rat brain and spinal cord, and the binding was significantly displaced by kainic acid. And, PSPA-4 increased intracellular Ca2+ concentration of cultured dorsal root ganglion neurons responding to glutamate, much higher than kainate in of them. Taken together, that PSPA-4 attenuated allodynia at low doses and induced allodynia at high doses via a binding site different from known kainate antagonists. In order to visualize the change of pain, a new analogue which has stronger radioactivity is necessary for in vitro autoradiography.The development of PSPA-4 will enable us to make a break through in the understanding of the action mechanism not only of Acro-A, but also of pain transmission in the periphery and central nervous system.