Prostaglandin D-2 inhibits prostaglandin E(2)-induced allodynia in conscious mice

We previously reported that intrathecal administration of prostaglandin (PG) D-2 and PGE(2) to conscious mice induced hyperalgesia (assessed by a hot-plate test) and that intrathecal administration of PGE(2) and PGF(2 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 PGD(2), PGE(2) and PGF(2 alpha). PGF(2 alpha) additively augmented the allodynia evoked by a submaximal dose (1 ng/mouse) of PGE(2). On the other hand, PGD(2) dose-dependently blocked the allodynia induced by a maximal dose (10 ng/mouse) of PGE(2), with an IC50 of 93.2 pg/mouse, but did not affect the PGE(2) (10 ng)-induced hyperalgesia at doses up to 10 ng. BW 245C, an agonist for PGD(2) receptors (DP receptors), but not another DP receptor agonist (ZK 110841) blocked the allodynia similarly. The blockade of PGE(2)-induced allodynia by 10 ng of PGD(2) 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 PGD(2). These results demonstrate that PGD(2) blocked the PGE(2)-evoked allodynia through DP receptors in the spinal cord, and they imply that endogenous PGD(2) may play an inhibitory role in the appearance of allodynia under physiological conditions.