title: Hematopoietic pannexin 1 function is critical for neuropathic pain.
abstract: Neuropathic pain symptoms respond poorly to available therapeutics, with most treated patients reporting unrelieved pain and significant impairment in daily life. Here, we show that Pannexin 1 (Panx1) in hematopoietic cells is required for pain-like responses following nerve injury in mice, and a potential therapeutic target. Panx1 knockout mice (Panx1-/-) were protected from hypersensitivity in two sciatic nerve injury models. Bone marrow transplantation studies show that expression of functional Panx1 in hematopoietic cells is necessary for mechanical hypersensitivity following nerve injury. Reconstitution of irradiated Panx1 knockout mice with hematopoietic Panx1-/-cells engineered to re-express Panx1 was sufficient to recover hypersensitivity after nerve injury; this rescue required expression of a Panx1 variant that can be activated by G protein-coupled receptors (GPCRs). Finally, chemically distinct Panx1 inhibitors blocked development of nerve injury-induced hypersensitivity and partially relieved this hypersensitivity after it was established. These studies indicate that Panx1 expressed in immune cells is critical for pain-like effects following nerve injury in mice, perhaps via a GPCR-mediated activation mechanism, and suggest that inhibition of Panx1 may be useful in treating neuropathic pain.
authors.affiliation: Department of Pharmacology, University of Virginia, Charlottesville, Virginia 22908, USA.
authors.forename: Janelle L
authors.initials: JL
authors.lastname: Weaver
authors.affiliation: Department of Microbiology, Immunology, Cancer Biology, University of Virginia, Charlottesville, Virginia 22908, USA.|Carter Immunology Center, University of Virginia, Charlottesville, Virginia 22908, USA.|Center for Cell Clearance, University of Virginia, Charlottesville, Virginia 22908, USA.
authors.forename: Sanja
authors.initials: S
authors.lastname: Arandjelovic
authors.affiliation: Department of Pharmacology, University of Virginia, Charlottesville, Virginia 22908, USA.
authors.forename: Gregory
authors.initials: G
authors.lastname: Brown
authors.affiliation: Department of Pharmacology, University of Virginia, Charlottesville, Virginia 22908, USA.
authors.forename: Suresh
authors.initials: S
authors.lastname: K Mendu
authors.affiliation: Department of Pharmacology, University of Virginia, Charlottesville, Virginia 22908, USA.
authors.forename: Michael
authors.initials: M
authors.lastname: S Schappe
authors.affiliation: Department of Microbiology, Immunology, Cancer Biology, University of Virginia, Charlottesville, Virginia 22908, USA.|Carter Immunology Center, University of Virginia, Charlottesville, Virginia 22908, USA.|Center for Cell Clearance, University of Virginia, Charlottesville, Virginia 22908, USA.
authors.forename: Monica W
authors.initials: MW
authors.lastname: Buckley
authors.affiliation: Department of Pharmacology, University of Virginia, Charlottesville, Virginia 22908, USA.
authors.forename: Yu-Hsin
authors.initials: YH
authors.lastname: Chiu
authors.affiliation: Department of Pharmacology, University of Virginia, Charlottesville, Virginia 22908, USA.
authors.forename: Shaofang
authors.initials: S
authors.lastname: Shu
authors.affiliation: Department of Pharmacology, University of Virginia, Charlottesville, Virginia 22908, USA.
authors.forename: Jin K
authors.initials: JK
authors.lastname: Kim
authors.affiliation: Department of Pharmacology, University of Virginia, Charlottesville, Virginia 22908, USA.
authors.forename: Joyce
authors.initials: J
authors.lastname: Chung
authors.affiliation: Department of Pharmacology, University of Virginia, Charlottesville, Virginia 22908, USA.
authors.forename: Julia
authors.initials: J
authors.lastname: Krupa
authors.affiliation: Department of Anesthesiology, University of Colorado, Aurora, Colorado 80045 USA.
authors.forename: Vesna
authors.initials: V
authors.lastname: Jevtovic-Todorovic
authors.affiliation: Department of Pharmacology, University of Virginia, Charlottesville, Virginia 22908, USA.
authors.forename: Bimal N
authors.initials: BN
authors.lastname: Desai
authors.affiliation: Department of Microbiology, Immunology, Cancer Biology, University of Virginia, Charlottesville, Virginia 22908, USA.|Carter Immunology Center, University of Virginia, Charlottesville, Virginia 22908, USA.|Center for Cell Clearance, University of Virginia, Charlottesville, Virginia 22908, USA.
authors.forename: Kodi S
authors.initials: KS
authors.lastname: Ravichandran
authors.affiliation: Department of Pharmacology, University of Virginia, Charlottesville, Virginia 22908, USA.
authors.forename: Douglas A
authors.initials: DA
authors.lastname: Bayliss
mesh_terms: D000818:Animals; D001854:Bone Marrow Cells / Q000378:metabolism; D017630:Connexins / Q000037:antagonists & inhibitors / Q000235:genetics* / Q000378:metabolism*; D004195:Disease Models, Animal; D005260:Female; D015870:Gene Expression; D006930:Hyperalgesia / Q000188:drug therapy / Q000209:etiology / Q000378:metabolism / Q000503:physiopathology; D008297:Male; D051379:Mice; D018345:Mice, Knockout; D009419:Nerve Tissue Proteins / Q000037:antagonists & inhibitors / Q000235:genetics* / Q000378:metabolism*; D009437:Neuralgia / Q000188:drug therapy / Q000209:etiology* / Q000378:metabolism* / Q000503:physiopathology; D059348:Peripheral Nerve Injuries / Q000150:complications; D015533:Transcriptional Activation
chemical_list: D017630:Connexins; D009419:Nerve Tissue Proteins; C503631:Panx1 protein, mouse