title: Spinal autophagy is differently modulated in distinct mouse models of neuropathic pain.
abstract: BACKGROUND
  Autophagy is a homeostatic degradative process essential for basal turnover of long-lived proteins and organelles as well as for removal of dysfunctional cellular components. Dysregulation of the autophagic machinery has been recently associated to several conditions including neurodegenerative diseases and cancer, but only very few studies have investigated its role in pain processing.
  
  
  RESULTS
  We previously described autophagy impairment at the spinal cord in the experimental model of neuropathic pain induced by spinal nerve ligation (SNL). In this study, we characterized the main autophagic markers in two other common experimental models of neuropathic pain, the chronic constriction injury (CCI) and the spared nerve injury (SNI). The different modulation of LC3-I, Beclin 1 and p62 suggested that autophagy is differentially affected in the spinal dorsal horn depending on the type of peripheral injury. Confocal analysis of p62 distribution in the spinal dorsal horn indicated its presence mainly in NeuN-positive cell bodies and occasionally in glial processes, thus suggesting a predominant expression in the neuronal compartment. Finally, we investigated the consequences of autophagy impairment on pain behaviour by using the autophagy blocker cloroquine. Intrathecal chloroquine injection in naïve mice induced spinal accumulation of LC3 and p62 paralleled by significant mechanical hypersensitivity thus confirming the block in autophagosome clearance and suggesting the participation of the autophagic process in spinal mechanisms of pain processing. Altogether, our data indicate that spinal autophagy is differentially altered in different experimental pain models of neuropathic pain and that this process may be relevant for pain control.
authors: Department of Health Sciences, University "Magna Græcia" of Catanzaro, 88100, Catanzaro, Italy. berliocchi@unicz.it.|Centre of Neuropharmacology of Normal and Pathological Synaptic Plasticity, University Consortium for Adaptive Disorders and Head Pain, 87036, Rende, Cosenza, Italy. berliocchi@unicz.it.
authors: Laura
authors: L
authors: Berliocchi
authors: Department of Pharmacy, Health and Nutritional Sciences, Section of Preclinical and Translational Pharmacology, University of Calabria, 87036, Rende, Cosenza, Italy. mariamaiaru@hotmail.it.
authors: Maria
authors: M
authors: Maiarù
authors: C. Mondino National Neurological Institute, Pavia, Italy. giuseppe.varano@hotmail.it.
authors: Giuseppe Pasquale
authors: GP
authors: Varano
authors: Department of Pharmacy, Health and Nutritional Sciences, Section of Preclinical and Translational Pharmacology, University of Calabria, 87036, Rende, Cosenza, Italy. rossella.russo@unical.it.
authors: Rossella
authors: R
authors: Russo
authors: Department of Health Sciences, University "Magna Græcia" of Catanzaro, 88100, Catanzaro, Italy. mtcorasa@unicz.it.
authors: Maria Tiziana
authors: MT
authors: Corasaniti
authors: Centre of Neuropharmacology of Normal and Pathological Synaptic Plasticity, University Consortium for Adaptive Disorders and Head Pain, 87036, Rende, Cosenza, Italy. g.bagetta@unical.it.|Department of Pharmacy, Health and Nutritional Sciences, Section of Preclinical and Translational Pharmacology, University of Calabria, 87036, Rende, Cosenza, Italy. g.bagetta@unical.it.
authors: Giacinto
authors: G
authors: Bagetta
authors: C. Mondino National Neurological Institute, Pavia, Italy. cristina.tassorelli@mondino.it.|Department of Brain and Behavioral Sciences, University of Pavia, Pavia, Italy. cristina.tassorelli@mondino.it.
authors: Cristina
authors: C
authors: Tassorelli
mesh_terms: D048868:Adaptor Proteins, Signal Transducing / Q000378:metabolism; D000818:Animals; D051017:Apoptosis Regulatory Proteins / Q000378:metabolism; D001343:Autophagy / Q000187:drug effects; D000071186:Beclin-1; D001522:Behavior, Animal / Q000187:drug effects; D015415:Biomarkers / Q000378:metabolism; D015153:Blotting, Western; D002738:Chloroquine / Q000008:administration & dosage / Q000494:pharmacology; D003720:Densitometry; D006360:Heat-Shock Proteins / Q000378:metabolism; D006930:Hyperalgesia / Q000150:complications / Q000473:pathology; D007278:Injections, Spinal; D008026:Ligation; D008297:Male; D008810:Mice, Inbred C57BL; D008869:Microtubule-Associated Proteins / Q000378:metabolism; D009407:Nerve Block; D009437:Neuralgia / Q000150:complications / Q000378:metabolism / Q000473:pathology*; D021381:Protein Transport / Q000187:drug effects; D000071456:Sequestosome-1 Protein; D013116:Spinal Cord / Q000187:drug effects / Q000378:metabolism / Q000473:pathology*; D066148:Spinal Cord Dorsal Horn / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D013127:Spinal Nerves / Q000293:injuries
chemical_list: D048868:Adaptor Proteins, Signal Transducing; D051017:Apoptosis Regulatory Proteins; D000071186:Beclin-1; C115010:Becn1 protein, mouse; D015415:Biomarkers; D006360:Heat-Shock Proteins; C480860:Map1lc3b protein, mouse; D008869:Microtubule-Associated Proteins; D000071456:Sequestosome-1 Protein; C101343:Sqstm1 protein, mouse; D002738:Chloroquine
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