We previously reported that intrathecal administration of
prostaglandin (PG) D2 and
PGE2 to conscious mice induced
hyperalgesia (assessed by a hot-plate test) and that intrathecal administration of
PGE2 and
PGF2 alpha induced
allodynia, a state of discomfort and
pain evoked by innocuous tactile stimuli. In the present study, we examined the relationships of
pain responses among
PGD2,
PGE2 and
PGF2 alpha,
PGF2 alpha additively augmented the
allodynia evoked by a submaximal dose (1 ng/mouse) of
PGE2. On the other hand,
PGD2 dose-dependently blocked the
allodynia induced by a maximal dose (10 ng/mouse) of
PGE2, with an IC50 of 93.2 pg/mouse, but did not affect the
PGE2 (10 ng)-induced
hyperalgesia at doses up to 10 ng.
BW 245C, an agonist for
PGD2 receptors (DP receptors), but not another DP receptor agonist (
ZK 110841) blocked the
allodynia similarly. The blockade of PGE2-induced
allodynia by 10 ng of
PGD2 was reversed by the potent and selective DP receptor antagonist
BW A868C, in a dose-dependent manner. Intrathecal administration of
BW A868C induced
allodynia by itself over a wide range, from 10 pg to 100 ng. and the
allodynia induced by 100 ng of
BW A868C was dose-dependently antagonized by
PGD2. These results demonstrate that
PGD2 blocked the PGE2-evoked
allodynia through DP receptors in the spinal cord, and they imply that endogenous
PGD2 may play an inhibitory role in the appearance of
allodynia under physiological conditions.