Spinal autophagy is differently modulated in distinct mouse models of neuropathic pain

Molecular Pain

Cristina Tassorelli⁴  Giacinto Bagetta³  Maria Tiziana Corasaniti¹  Rossella Russo³  Giuseppe Pasquale Varano⁵  Maria Maiarù³  Laura Berliocchi² 

[1] Department of Health Sciences, University “Magna Græcia” of Catanzaro, 88100 Catanzaro, Italy;Centre of Neuropharmacology of Normal and Pathological Synaptic Plasticity, University Consortium for Adaptive Disorders and Head Pain, 87036 Rende, Cosenza, Italy;Department of Pharmacy, Health and Nutritional Sciences, Section of Preclinical and Translational Pharmacology, University of Calabria, 87036 Rende, Cosenza, Italy;Department of Brain and Behavioral Sciences, University of Pavia, Pavia, Italy;C. Mondino National Neurological Institute, Pavia, Italy

关键词: Chloroquine;    Beclin 1;    SQSTM1/p62;    LC3;    Autophagy;    Neuropathic pain;    Spared nerve injury;    Chronic constriction injury;    Spinal nerve ligation;   

Others  :  1135294
DOI  :  10.1186/1744-8069-11-3

 received in 2014-09-14, accepted in 2015-01-06,  发布年份 2015

【 摘 要 】

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.

【 授权许可】

   
2015 Berliocchi et al.; licensee BioMed Central.

【 图 表 】

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