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

Laura Berliocchi, Maria Maiarù, Giuseppe Pasquale Varano, Rossella Russo, Maria Tiziana Corasaniti, Giacinto Bagetta, Cristina Tassorelli

Research output: Contribution to journalArticle

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.

Original languageEnglish
Article number3
JournalMolecular Pain
Volume11
Issue number1
DOIs
Publication statusPublished - Feb 2 2015

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Keywords

  • Autophagy
  • Beclin 1
  • Chloroquine
  • Chronic constriction injury
  • LC3
  • Neuropathic pain
  • Spared nerve injury
  • Spinal nerve ligation
  • SQSTM1/p62

ASJC Scopus subject areas

  • Anesthesiology and Pain Medicine
  • Molecular Medicine
  • Cellular and Molecular Neuroscience

Cite this

Berliocchi, L., Maiarù, M., Varano, G. P., Russo, R., Corasaniti, M. T., Bagetta, G., & Tassorelli, C. (2015). Spinal autophagy is differently modulated in distinct mouse models of neuropathic pain. Molecular Pain, 11(1), [3]. https://doi.org/10.1186/1744-8069-11-3