Abnormal Pain Sensation in Mice Lacking the Prokineticin Receptor PKR2: Interaction of PKR2 with Transient Receptor Potential TRPV1 and TRPA1. (10th February 2020)

• Record Type: Journal Article
• Authors: Maftei, Daniela; Vellani, Vittorio; Artico, Marco; Giacomoni, Chiara; Severini, Cinzia; Lattanzi, Roberta
• Is Part Of: Neuroscience. Volume 427(2020)
• Page Start: 16
• Page End: 28
• Publication Date: 2020-02-10
• Subjects: CGRP calcitonin gene related peptide -- DRG dorsal root ganglia -- EG-VEGF endocrine gland-derived vascular endothelial growth factor -- PKRs prokineticin receptors -- PNS peripheral nervous system -- TRPA1 transient receptor potential ankyrin 1 ion channel -- WT wild type -- ANOVA analysis of variance -- CFA Complete Freund's Adjuvant -- CNS central nervous system -- GPCR G-protein coupled receptors -- MIT-1 Mamba Intestinal Toxin-1 -- MO mustard oil -- PKs prokineticins -- PROK1 prokineticin 1 -- PROK2 prokineticin 2 -- PKR1 prokineticin receptor 1 -- PKR2 prokineticin receptor 2 -- PWT paw withdrawal threshold -- TRPV1 transient receptor potential vanilloid 1 channel; pain -- nociception -- prokineticin system -- prokineticin receptor 2 -- inflammation; Neurochemistry -- Periodicals; Neurophysiology -- Periodicals; Neurology -- Periodicals; Neurochimie -- Périodiques; Neurophysiologie -- Périodiques; Neurochemistry; Neurophysiology; Electronic journals; Periodicals; Electronic journals; 612.8
• DOI: 10.1016/j.neuroscience.2019.12.003
• Languages: English
• ISSNs: 0306-4522

Abstract

Highlights: Pkr2-null mice are less responsive to noxious thermal hot and cold stimuli compared to wild type littermates. Pkr2-null mice are less responsive to noxious chemical stimuli compared to wild type littermates. Pkr2-null mice are less sensitive to inflammatory-induced heat hyperalgesia compared to wild type littermates. Pkr2-null mice do not develop inflammatory-induced tactile allodynia. PKR2 functionally interacts with TRP channels contributing to nociceptor sensitization and pain development. Abstract: The amphibian Bv8 and the mammalian prokineticin 1 (PROK1) and 2 (PROK2) are new chemokine-like protein ligands acting on two G protein-coupled receptors, prokineticin receptor 1 (PKR1) and 2 (PKR2), participating to the mediation of diverse physiological and pathological processes. Prokineticins (PKs), specifically activating the prokineticin receptors (PKRs) located in several areas of the central and peripheral nervous system associated with pain, play a fundamental role in nociception. In this paper, to improve the understanding of the prokineticin system in the neurobiology of pain, we investigated the role of PKR2 in pain perception using pkr2 gene-deficient mice. We observed that, compared to wildtype, pkr2-null mice were more resistant to nociceptive sensitization to temperatures ranging from 46 to 48 °C, to capsaicin and to protons, highlighting a positive interaction between PKR2 and the non-selective cation channels TRPV1. Moreover, PKR2 knock-out mice showed reduced nociceptive response to cold temperature (4 °C) and to mustard oil-induced inflammatory hyperalgesia, suggesting a functional interaction between PKR2 and transient receptor potential ankyrin 1 ion (TRPA1) channels. This notion was supported by experiments in dorsal root ganglia (DRG) cultures from pkr1 and–pkr2-null mice, demonstrating that the percentage of Bv8-responsive DRG neurons which were also responsive to mustard oil was much higher in PKR1−/− than in PKR2−/− mice. Taken together, these findings suggest a functional interaction between PKR2 and TRP channels in the development of hyperalgesia. Drugs able to directly or indirectly block these targets and/or their interactions may represent potential analgesics.