title: Glial pannexin1 contributes to tactile hypersensitivity in a mouse model of orofacial pain.
abstract: Drug studies in animal models have implicated pannexin1 (Panx1) in various types of pain, including trigeminal hypersensitivity, neuropathic pain and migraine. However, the tested drugs have limited specificity and efficacy so that direct evidence for Panx1 contribution to pain has been lacking. We here show that tactile hypersensitivity is markedly attenuated by deletion of Panx1 in a mouse model of chronic orofacial pain; in this model, trigeminal ganglion Panx1 expression and function are markedly enhanced. Targeted deletion of Panx1 in GFAP-positive glia or in neurons revealed distinct effects. Panx1 deletion in GFAP-positive glia cells prevented hypersensitivity completely, whereas deletion of neuronal Panx1 reduced baseline sensitivity and the duration of hypersensitivity. In trigeminal ganglia with genetically encoded Ca2+indicator in GFAP-positive glia or in neurons, both cell populations were found to be hyperactive and hyper-responsive to ATP. These novel findings reveal unique roles for GFAP-positive glial and neuronal Panx1 and describe new chronic pain targets for cell-type specific intervention in this often intractable disease.
authors.affiliation: Dominick P. Purpura Department of Neuroscience, Albert Einstein College of Medicine, Bronx, NY, 10461, USA.
authors.forename: Regina
authors.initials: R
authors.lastname: Hanstein
authors.affiliation: Laboratory of Experimental Surgery, Department of Surgery, Hadassah University Hospital, Jerusalem, Israel.
authors.forename: Menachem
authors.initials: M
authors.lastname: Hanani
authors.affiliation: Dominick P. Purpura Department of Neuroscience, Albert Einstein College of Medicine, Bronx, NY, 10461, USA.
authors.forename: Eliana
authors.initials: E
authors.lastname: Scemes
authors.affiliation: Dominick P. Purpura Department of Neuroscience, Albert Einstein College of Medicine, Bronx, NY, 10461, USA.
authors.forename: David C
authors.initials: DC
authors.lastname: Spray
mesh_terms: D000818:Animals; D059350:Chronic Pain / Q000235:genetics / Q000378:metabolism* / Q000473:pathology; D017630:Connexins / Q000096:biosynthesis* / Q000235:genetics; D005786:Gene Expression Regulation; D006941:Hyperesthesia / Q000235:genetics / Q000378:metabolism* / Q000473:pathology; D051379:Mice; D008822:Mice, Transgenic; D009419:Nerve Tissue Proteins / Q000096:biosynthesis* / Q000235:genetics; D009457:Neuroglia / Q000378:metabolism* / Q000473:pathology; D009474:Neurons / Q000378:metabolism* / Q000473:pathology; D012668:Trigeminal Ganglion / Q000378:metabolism* / Q000473:pathology
chemical_list: D017630:Connexins; D009419:Nerve Tissue Proteins; C503631:Panx1 protein, mouse