title: Bv8/PK2 and prokineticin receptors: a druggable pronociceptive system.
abstract: Mammalian Bv8 (also called prokineticin 2) is a secreted protein that regulates diverse biological processes including pain perception. It belongs to a new family of chemokines, which activate two G-protein linked receptors (prokineticin receptor 1 and 2, PKR1 and PKR2) expressed in regions of the nervous system associated with pain and in cells participating to immuno-inflammatory responses. Primary sensitive neurons co-express PKRs and the transient potential receptor vanilloid 1, cooperating in nociceptor sensitization. Bv8, strongly upregulated in neutrophils and other inflammatory cells, is a main pronociceptive mediator in inflamed tissues, where it sensitizes peripheral nociceptors, stimulates neutrophil chemotaxis and modulates the release of inflammatory and pronociceptive cytokines. Availability of a nonpeptide PKR antagonist, leading to blockade of the Bv8/PKR system, ameliorates pain arising from tissue injury and reduces the time required for recovery from injury.
authors.affiliation: Department of Physiology and Pharmacology Vittorio Erspamer, Sapienza, University of Rome, P.le A. Moro 5, 00185 Rome, Italy. lucia.negri@uniroma1.it
authors.forename: Lucia
authors.initials: L
authors.lastname: Negri
authors.forename: Roberta
authors.initials: R
authors.lastname: Lattanzi
mesh_terms: D000700:Analgesics / Q000494:pharmacology*; D000818:Animals; D005768:Gastrointestinal Hormones / Q000378:metabolism*; D006801:Humans; D009479:Neuropeptides / Q000378:metabolism*; D010146:Pain / Q000188:drug therapy* / Q000378:metabolism; D043562:Receptors, G-Protein-Coupled / Q000378:metabolism*; D018000:Receptors, Peptide / Q000378:metabolism*
chemical_list: D000700:Analgesics; D005768:Gastrointestinal Hormones; D009479:Neuropeptides; C423608:PROK2 protein, human; C486586:Prok2 protein, mouse; D043562:Receptors, G-Protein-Coupled; D018000:Receptors, Peptide