Blood-spinal Cord Barrier Breakdown and Pericyte Deficiency in Peripheral Neuropathy

Ann N Y Acad Sci. 2017 Oct;1405(1):71-88. doi: 10.1111/nyas.13436. Epub 2017 Jul 28.

Abstract

The blood-spinal cord barrier (BSCB) prevents leakage of molecules, such as pronociceptive mediators, into the spinal cord, but its role in the pathophysiology of neuropathic pain is not completely understood. Rats with chronic constriction injury (CCI) develop mechanical allodynia, thermal hypersensitivity, and reduced motor performance (Rota-Rod test) compared with sham-injured mice-similar to mice with spared nerve injury (SNI). The BSCB becomes permeable for small and large tracers 1 day after nerve ligation. Messenger RNA (mRNA) expression of tight junction proteins (TJPs) occludin, claudin-1, claudin-5, claudin-19, tricellulin, and ZO-1 significantly declines 7-14 days after CCI or SNI. ZO-1 and occludin are reduced in the cell membrane. In capillaries isolated from the spinal cord, immunoreactivity of claudin-5 and ZO-1 is fainter. In parallel, the number of platelet-derived growth factor receptor β (PDGF-β)+ and CD13+ pericytes in the spinal cord drops. Reduced levels of cytosolic transcription factors like β-catenin, but not SMAD4 and SLUG, could account for reduced TJP mRNA. In summary, neuropathy-induced allodynia/hypersensitivity is accompanied by a loss of pericytes in the spinal cord and a leaky BSCB. A better understanding of these pathways and mechanisms in neuropathic pain might foster the design of novel treatments to maintain spinal cord homeostasis.

Keywords: capillaries; nerve injury; pain; tight junction protein; β-catenin.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Male
  • Mice
  • Mice, Inbred C57BL
  • Motor Skills / physiology
  • Pericytes / metabolism*
  • Pericytes / pathology
  • Peripheral Nervous System Diseases / metabolism*
  • Peripheral Nervous System Diseases / pathology
  • Permeability
  • Rats
  • Rats, Wistar
  • Rotarod Performance Test
  • Smad4 Protein / metabolism
  • Snail Family Transcription Factors / metabolism
  • Spinal Cord / metabolism*
  • Spinal Cord / pathology
  • Tight Junction Proteins / metabolism*
  • beta Catenin / metabolism

Substances

  • Smad4 Protein
  • Snai2 protein, rat
  • Snail Family Transcription Factors
  • Tight Junction Proteins
  • beta Catenin