Inhibition of nociceptin-induced allodynia in conscious mice by prostaglandin D2.
1. We recently showed that intrathecal administration of nociceptin induced allodynia by innocuous tactile stimuli and hyperalgesia by noxious thermal stimuli in conscious mice. In the present study, we examined the effect of prostaglandins on nociceptin-induced allodynia and hyperalgesia. 2. Prostaglandin D2 (PGD2) blocked the allodynia induced by nociceptin in a dose-dependent manner with an IC50 of 26 ng kg(-1), but did not affect the nociceptin-induced hyperalgesia at doses up to 500 ng kg(-1). BW 245C (an agonist for PGD (DP) receptor) blocked the allodynia with an IC50 of 83 ng kg(-1). 3. The blockade of nociceptin-induced allodynia by PGD2 was reversed by the potent and selective DP-receptor antagonist BW A868C in a dose-dependent manner with an ED50 of 42.8 ng kg(-1). 4. Glycine (500 ng kg[-1]) almost completely blocked the nociceptin-induced allodynia. A synergistic effect on the inhibition of nociceptin-evoked allodynia was observed between glycine and PGD2 at below effective doses. 5. Dibutyryl cyclic AMP, but not dibutyryl cyclic GMP, blocked the nociceptin-induced allodynia with an IC50 of 2.9 microg kg(-1). 6. PGE2, PGF2alpha, butaprost (an EP2 agonist) and cicaprost (a PGI receptor agonist) did not affect the nociceptin-induced allodynia. 7. These results demonstrate that PGD2 inhibits the nociceptin-evoked allodynia through DP receptors in the spinal cord and that glycine may be involved in this inhibition.
Minami
T
T
Department of Anesthesiology, Osaka Medical College, Japan.
Okuda-Ashitaka
E
E
Nishizawa
M
M
Mori
H
H
Ito
S
S
D000818:Animals; D003994:Bucladesine / Q000494:pharmacology; D003995:Dibutyryl Cyclic GMP / Q000494:pharmacology; D005998:Glycine / Q000494:pharmacology; D006930:Hyperalgesia / Q000139:chemically induced; D008297:Male; D051379:Mice; D009292:Narcotic Antagonists; D018847:Opioid Peptides / Q000037:antagonists & inhibitors / Q000494:pharmacology*; D010146:Pain / Q000139:chemically induced / Q000517:prevention & control*; D015230:Prostaglandin D2 / Q000494:pharmacology*; D000097629:Nociceptin
D003994:Bucladesine; D003995:Dibutyryl Cyclic GMP; D005998:Glycine; D009292:Narcotic Antagonists; D018847:Opioid Peptides; D015230:Prostaglandin D2; D000097629:Nociceptin