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.