BLOCKADE BY ONO-NT-012, A UNIQUE PROSTANOID ANALOG, OF PROSTAGLANDIN E(2)-INDUCED ALLODYNIA IN CONSCIOUS MICE

1 Intrathecal (i.t.) administration of prostaglandin E(2) (PGE(2)) to conscious mice was reported to induce allodynia, a state of discomfort and pain evoked by innocuous tactile stimuli through prostaglandin E receptor subtype EP(1) and hyperalgesia through prostaglandin E receptor subtypes EP(2) and/or EP(3). In the present study, we investigated the effects of an EP(1) antagonist on these sensory disorders by use of ONO-NT-012 or AH6809. 2 ONO-NT-012 dose-dependently antagonized the PGE(2)-induced allodynia but had no effect on the PGE(2)-induced hyperalgesia by the hot plate test. On the other hand, AH6809 blocked the PGE(2)-induced hyperalgesia at the highest dose examined (50 mu g kg(-1)) but had no effect on the PGE(2)-induced allodynia. The i.t. injection of AH6809 or ONO-NT-012 alone did not have any effect on the response to noxious or innocuous stimuli. 3 Increasing doses (5 pg kg(-1)-500 ng kg(-1)) of ONO-NT-012 produced parallel shifts to the right of the dose-response curves to PGE(2). The Schild plot regression line was linear and the slope was close to unity. The pA(2) value against PGE(2) was calculated to be 9.96. 4 The present study demonstrates that i.t. administration of PGE(2) exerts allodynia through EP(1) in the mouse spinal cord and that ONO-NT-012 is a highly potent, simple competitive antagonist for the PGE(2)-induced allodynia.