Prostaglandin D2 inhibits prostaglandin E2-induced allodynia in conscious mice.
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.
Minami
T
T
Department of Anesthesiology, Osaka Medical College, Japan.
Okuda-Ashitaka
E
E
Mori
H
H
Ito
S
S
Hayaishi
O
O
D000322:Adrenergic Agonists / Q000494:pharmacology; D000818:Animals; D015237:Dinoprost / Q000494:pharmacology; D015232:Dinoprostone / Q000494:pharmacology*; D004305:Dose-Response Relationship, Drug; D005998:Glycine / Q000494:pharmacology; D006827:Hydantoins / Q000494:pharmacology; D008297:Male; D051379:Mice; D016202:N-Methylaspartate / Q000494:pharmacology; D010146:Pain / Q000503:physiopathology*; D015230:Prostaglandin D2 / Q000494:pharmacology*; D013116:Spinal Cord / Q000502:physiology; D014851:Wakefulness; D005680:gamma-Aminobutyric Acid / Q000494:pharmacology
D000322:Adrenergic Agonists; D006827:Hydantoins; C058848:BW A868C; D005680:gamma-Aminobutyric Acid; D016202:N-Methylaspartate; D015237:Dinoprost; D015232:Dinoprostone; D015230:Prostaglandin D2; D005998:Glycine