title: Pannexin 1: a novel participant in neuropathic pain signaling in the rat spinal cord.
abstract: Pannexin 1 (panx1) is a large-pore membrane channel expressed in many tissues of mammals, including neurons and glial cells. Panx1 channels are highly permeable to calcium and adenosine triphosphatase (ATP); on the other hand, they can be opened by ATP and glutamate, two crucial molecules for acute and chronic pain signaling in the spinal cord dorsal horn, thus suggesting that panx1 could be a key component for the generation of central sensitization during persistent pain. In this study, we examined the effect of three panx1 blockers, namely, 10panx peptide, carbenoxolone, and probenecid, on C-reflex wind-up activity and mechanical nociceptive behavior in a spared nerve injury neuropathic rat model involving sural nerve transection. In addition, the expression of panx1 protein in the dorsal horn of the ipsilateral lumbar spinal cord was measured in sural nerve-transected and sham-operated control rats. Sural nerve transection resulted in a lower threshold for C-reflex activation by electric stimulation of the injured hindpaw, together with persistent mechanical hypersensitivity to pressure stimuli applied to the paw. Intrathecal administration of the panx1 blockers significantly depressed the spinal C-reflex wind-up activity in both neuropathic and sham control rats, and decreased mechanical hyperalgesia in neuropathic rats without affecting the nociceptive threshold in sham animals. Western blotting showed that panx1 was similarly expressed in the dorsal horn of lumbar spinal cord from neuropathic and sham rats. The present results constitute the first evidence that panx1 channels play a significant role in the mechanisms underlying central sensitization in neuropathic pain.
authors.affiliation: Laboratory of Neurobiology, Department of Biology, Faculty of Chemistry and Biology, University of Santiago of Chile, Santiago, Chile.
authors.forename: David
authors.initials: D
authors.lastname: Bravo
authors.affiliation: Laboratory of Neurobiology, Department of Biology, Faculty of Chemistry and Biology, University of Santiago of Chile, Santiago, Chile.
authors.forename: Paula
authors.initials: P
authors.lastname: Ibarra
authors.affiliation: Laboratory of Neurobiology, Department of Biology, Faculty of Chemistry and Biology, University of Santiago of Chile, Santiago, Chile.
authors.forename: Jeffri
authors.initials: J
authors.lastname: Retamal
authors.affiliation: Program of Molecular and Clinical Pharmacology, Institute of Biomedical Sciences, Faculty of Medicine, University of Chile, Santiago, Chile.
authors.forename: Teresa
authors.initials: T
authors.lastname: Pelissier
authors.affiliation: Laboratory of Neurobiology, Department of Biology, Faculty of Chemistry and Biology, University of Santiago of Chile, Santiago, Chile.
authors.forename: Claudio
authors.initials: C
authors.lastname: Laurido
authors.affiliation: Laboratory of Neurobiology, Department of Biology, Faculty of Chemistry and Biology, University of Santiago of Chile, Santiago, Chile.
authors.forename: Alejandro
authors.initials: A
authors.lastname: Hernandez
authors.affiliation: Laboratory of Neurobiology, Department of Biology, Faculty of Chemistry and Biology, University of Santiago of Chile, Santiago, Chile. Electronic address: luis.constandil@usach.cl.
authors.forename: Luis
authors.initials: L
authors.lastname: Constandil
mesh_terms: D000818:Animals; D002229:Carbenoxolone / Q000494:pharmacology / Q000627:therapeutic use*; D017630:Connexins / Q000037:antagonists & inhibitors* / Q000378:metabolism; D006930:Hyperalgesia / Q000188:drug therapy* / Q000209:etiology / Q000378:metabolism; D008297:Male; D009419:Nerve Tissue Proteins / Q000037:antagonists & inhibitors* / Q000378:metabolism; D009437:Neuralgia / Q000188:drug therapy* / Q000209:etiology / Q000378:metabolism; D017288:Pain Threshold / Q000187:drug effects; D059348:Peripheral Nerve Injuries / Q000150:complications; D020671:Posterior Horn Cells / Q000187:drug effects / Q000378:metabolism; D011339:Probenecid / Q000494:pharmacology / Q000627:therapeutic use*; D051381:Rats; D017207:Rats, Sprague-Dawley; D012018:Reflex / Q000187:drug effects*; D013116:Spinal Cord / Q000187:drug effects* / Q000378:metabolism
chemical_list: D017630:Connexins; D009419:Nerve Tissue Proteins; C479936:pannexin 1, rat; D002229:Carbenoxolone; D011339:Probenecid
keywords: 10panx; C-reflex; Carbenoxolone; Central sensitization; Neuropathic pain; Pannexin 1; Paw pressure threshold; Probenecid