Diabetes-induced Neuropathic Mechanical Hyperalgesia Depends on P2X4 Receptor Activation in Dorsal Root Ganglia. (1st February 2019)

• Record Type: Journal Article
• Authors: Teixeira, Juliana Maia; dos Santos, Gilson Gonçalves; Neves, Amanda Ferreira; Athie, Maria Carolina Pedro; Bonet, Ivan José Magayewski; Nishijima, Catarine Massucato; Farias, Felipe Hertzing; Figueiredo, Jozi Godoy; Hernandez-Olmos, Victor; Alshaibani, Samer; Tambeli, Cláudia Herrera; Müller, Christa E.; Parada, Carlos Amílcar
• Is Part Of: Neuroscience. Volume 398(2019)
• Page Start: 158
• Page End: 170
• Publication Date: 2019-02-01
• Subjects: ANOVA analysis of variance -- ATP adenosine-5′-triphosphate -- BSA bovine serum albumin -- BzATP 2′(3′)-O-(4-benzoylbenzoyl) adenosine 5′-triphosphate triethylammonium salt -- DAPI 4′, 6-diamidino-2-phenylindole -- DMEM Dulbecco's modified eagle's medium -- DMSO dimethyl sulfoxide -- DRG dorsal root ganglia -- EDTA ethylenediamine tetraacetic acid -- gl. ganglionar -- i.p. intraperitoneal -- i.t. intrathecal -- IASP International Association for Study of Pain -- IL-1β interleukin 1β -- ODN oligodeoxynucleotides -- P2X4R P2X4 receptor -- P2X7R P2X7 receptor -- PBS phosphate-buffered saline -- PDN peripheral diabetic neuropathy -- PFA paraformaldehyde -- PNS peripheral nervous system -- SGC satellite glial cells -- STZ streptozotocin -- TRPV-1 transient receptor potential cation channel subfamily V member 1; P2X4 receptor -- peripheral diabetic neuropathy -- mechanical hyperalgesia -- satellite glial cells -- dorsal root ganglion -- streptozotocin; Neurochemistry -- Periodicals; Neurophysiology -- Periodicals; Neurology -- Periodicals; Neurochimie -- Périodiques; Neurophysiologie -- Périodiques; Neurochemistry; Neurophysiology; Electronic journals; Periodicals; Electronic journals; 612.8
• DOI: 10.1016/j.neuroscience.2018.12.003
• Languages: English
• ISSNs: 0306-4522

Abstract

Highlights: The P2X4 receptor blockade reduces the diabetes-induced neuropathic mechanical hyperalgesia. P2X4 receptor expression is increased in the dorsal root ganglia (DRG) of diabetic neuropathic rats. The P2X4 receptor seems to be expressed on satellite glial cells, which are surrounding DRG neurons. P2X4 receptor blockers might be effective on peripheral diabetic neuropathy. Abstract: Peripheral diabetic neuropathy (PDN) manifests in 50–60% of type I and II diabetic patients and is the major cause of limb amputation. Adequate therapy for PDN is a current challenge. There are evidences that the activation of the P2X4 receptor (P2X4R) expressed on microglial cells of the central nervous system takes part in the development of neuropathic pain. However, there is an open question: Is P2X4R activation on dorsal root ganglia (DRG) involved in the development of neuropathic pain? To answer this question, this study verified the involvement of P2X4R expressed in DRG cells on diabetes-induced neuropathic mechanical hyperalgesia in rats. We found that intrathecal or ganglionar (L5-DRG) administration of a novel P2X4R antagonist (PSB-15417) or intrathecal administration of oligodeoxynucleotides (ODN)-antisense against the P2X4R reversed diabetes-induced neuropathic mechanical hyperalgesia. The DRG of the diabetic neuropathic rats showed an increase in P2X4R expression, and the DRG immunofluorescence suggested that P2X4R is expressed mainly in satellite glial cells (SGC). Finally, our study showed a functional expression of P2X4R in SGCs of the rat's DRG, because the P2X4R agonist BzATP elicits an increase in intracellular calcium concentration in SGCs, which was reduced by PSB-15417. These findings indicate that P2X4R activation in DRG is essential to diabetes-induced neuropathic mechanical hyperalgesia. Therefore, this purinergic receptor in DRG could be an interesting therapeutic target for quaternary P2X4R antagonists that do not cross the hematoencephalic barrier, for the control of neuropathic pain, preserving central nervous system functions.