Prostaglandin D2 inhibits prostaglandin E2-induced allodynia in conscious mice
Minami, T.; Okuda-Ashitaka, E.; Mori, H.; Ito, S.; Hayaishi, O.
Journal of Pharmacology and Experimental Therapeutics 278(3): 1146-1152
1996
ISSN/ISBN: 0022-3565 PMID: 8819497 Document Number: 464632
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-2alpha 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-2alpha. PGF-2alpha 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 IC-50 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.