Inhibition of nociceptin‐induced allodynia in conscious mice by prostaglandin D₂

Abstract

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 e ect of prostaglandins on nociceptin-induced allodynia and hyperalgesia. 2 Prostaglandin D 2 (PGD 2 ) blocked the allodynia induced by nociceptin in a dose-dependent manner with an IC 50 of 26 ng kg 71 , but did not a ect the nociceptin-induced hyperalgesia at doses up to 500 ng kg 71 . BW 245C (an agonist for PGD (DP) receptor) blocked the allodynia with an IC 50 of 83 ng kg 71 . 3 The blockade of nociceptin-induced allodynia by PGD 2 was reversed by the potent and selective DPreceptor antagonist BW A868C in a dose-dependent manner with an ED 50 of 42.8 ng kg 71 . 4 Glycine (500 ng kg 71 ) almost completely blocked the nociceptin-induced allodynia. A synergistic e ect on the inhibition of nociceptin-evoked allodynia was observed between glycine and PGD 2 at below e ective doses. 5 Dibutyryl cyclic AMP, but not dibutyryl cyclic GMP, blocked the nociceptin-induced allodynia with an IC 50 of 2.9 mg kg 71 . 6 PGE 2 , PGF 2a , butaprost (an EP 2 agonist) and cicaprost (a PGI receptor agonist) did not a ect the nociceptin-induced allodynia. 7 These results demonstrate that PGD 2 inhibits the nociceptin-evoked allodynia through DP receptors in the spinal cord and that glycine may be involved in this inhibition.

The opioid peptide nociceptin/orphanin FQ mediates prostaglandin E2‐induced allodynia, tactile pain associated with nerve injury

“…(iii) The PGE 2 ‐ and N/OFQ‐induced allodynia were dose‐dependently blocked by D‐AP5, an NMDA‐receptor antagonist, and were not observed in mice lacking NMDA receptors containing NR2A (Minami et al ., 1999, 2000). (iv) PGD 2 blocked the PGE 2 ‐ and N/OFQ‐induced allodynia (Minami et al ., 1996, 1997). (v) Besides N/OFQ, nocistatin is cleaved from ppN/OFQ and was found to block PGE 2 ‐ and N/OFQ‐induced allodynia (Okuda‐Ashitaka et al ., 1998).…”

Physiological Roles of Group X-secreted Phospholipase A2 in Reproduction, Gastrointestinal Phospholipid Digestion, and Neuronal Function

“…However, we do not fully rule out the possibility that sPLA 2 -X may affect the "local" production of some lipid mediators linked to pain sensation. It is known that PGE 2 and PGI 2 are critically involved in pain transmission (40 -43) and that PGD 2 modulates PGE 2 -evoked allodynia (44,45). These prostanoids stimulate a population of TRPV1-positive, C-fiber DRG neurons to release peptide neurotransmitters (80).…”

International Union of Basic and Clinical Pharmacology. LXXXIII: Classification of Prostanoid Receptors, Updating 15 Years of Progress

“…A pharmacological rationale for the various central effects of PGD 2 and its analogs is therefore tenable. These effects include sleep regulation (Urade and Hayaishi, 1999), neuroprotection (Liang et al, 2005b;Saleem et al, 2007b;Thura et al, 2009) allodynia (Minami et al, 1997), and hyperalgesia (Telleria-Diaz et al, 2008). DP 1 receptor involvement in neurotransmission is not limited to the CNS, and a local effect on pruritus has been reported Sugimoto et al, 2007).…”