Blockade by ONO-NT-012, a unique prostanoid analogue, of prostaglandin E2-induced allodynia in conscious mice

Abstract 1. Intrathecal (i.t.) administration of prostaglandin E2 (PGE2) to conscious mice was reported to induce allodynia, a state of discomfort and pain evoked by innocuous tactile stimuli through prostaglandin E receptor subtype EP1 and hyperalgesia through prostaglandin E receptor subtypes EP2 and/or EP3. In the present study, we investigated the effects of an EP1 antagonist on these sensory disorders by use of ONO-NT-012 or AH6809. 2. ONO-NT-012 dose-dependently antagonized the PGE2-induced allodynia but had no effect on the PGE2-induced hyperalgesia by the hot plate test. On the other hand, AH6809 blocked the PGE2-induced hyperalgesia at the highest dose examined (50 micrograms kg-1) but had no effect on the PGE2-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 PGE2. The Schild plot regression line was linear and the slope was close to unity. The pA2 value against PGE2 was calculated to be 9.96. 4. The present study demonstrates that i.t. administration of PGE2 exerts allodynia through EP1 in the mouse spinal cord and that ONO-NT-012 is a highly potent, simple competitive antagonist for the PGE2-induced allodynia.