Central nociceptive role of prostacyclin (IP) receptor induced by peripheral inflammation

Abstract

Prostacyclin (PGI2) is well known to play crucial roles in induction of edema and pain behavior in the periphery. In the present study, we investigated the central role of PGI2 in inflammatory pain. Intraplantar injection of carrageenan markedly induced the expression of prostacyclin receptor (IP receptor) mRNA with the maximum at 6 h, coincidently induction of the inducible form of cyclooxygenase (COX-2), although IP receptor mRNA was weakly expressed in the spinal cord of naive mice. Intrathecal administration of the IP agonist cicaprost induced mechanical hyperalgesia 6 h after carrageenan injection. These results suggest that PGI2 is involved in pain transmission at the spinal cord following expression of IP receptor mRNA induced by peripheral inflammation.

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

“…Results obtained with IP antagonists in rat models of pain and inflammation Pulichino et al, 2006) are consistent with results obtained in the IP(Ϫ/Ϫ) mice studies. The involvement of IP receptors in pain and hyperalgesia are supported by IP expression studies Doi et al, 2002) and functional studies on neurons conducting at C velocity . Studies on dorsal root ganglia support an IP receptor role in sensitization of sensory neurons Rowlands et al, 2001;Nakae et al, 2005).…”

Pituitary Adenylate Cyclase-Activating Polypeptide Is Required for the Development of Spinal Sensitization and Induction of Neuropathic Pain

“…Mechanical sensitivity was determined with calibrated von Frey filaments, using the up-down paradigm of Chaplan et al (1994). The inflammatory pain model was made by intraplantar injection of -carrageenan (0.4 mg/40 l) into the left hindpaw (Doi et al, 2002). The neuropathic pain model was made as described previously .…”

Role of G protein-coupled receptors in inflammation

“…Prostacyclin (PGI), which acts on G protein-coupled IP receptor, is another arachdonic metabolite produced during inflammation that plays a central nociceptive role [42] . Mice lacking the IP receptor display altered pain perception as well as inflammatory responses [43] .…”