☆ 4.3 Article

Quantifying blood-spinal cord barrier permeability after peripheral nerve injury in the living mouse

MOLECULAR PAIN (2014)

Journal

MOLECULAR PAIN

Volume 10, Issue -, Pages -

Publisher

SAGE PUBLICATIONS INC

DOI: 10.1186/1744-8069-10-60

Keywords

Blood-spinal cord barrier permeability; Dynamic contrast-enhanced MRI; Gd-DTPA; Mouse; Neuropathic pain; Peripheral nerve injury; Spinal cord

Funding

Canadian Foundation for Innovation
Ontario Innovation Trust
Canadian Institutes of Health Research
Genome Canada
National Institutes of Healthy
Ontario Research Fund
Hospital for Sick Children
CIHR

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Abstract

Background: Genetic polymorphisms, gender and age all influence the risk of developing chronic neuropathic pain following peripheral nerve injury (PNI). It is known that there are significant inter-strain differences in pain hypersensitivity in strains of mice after PNI. In response to PNI, one of the earliest events is thought to be the disruption of the blood-spinal cord barrier (BSCB). The study of BSCB integrity after PNI may lead to a better understanding of the mechanisms that contribute to chronic pain. Results: Here we used in vivo dynamic contrast-enhanced magnetic resonance imaging (DCE-MRI) to establish a timecourse for BSCB permeability following PNI, produced by performing a spared nerve injury (SNI). From this longitudinal study, we found that the SNI group had a significant increase in BSCB permeability over time throughout the entire spinal cord. The BSCB opening had a delayed onset and the increase in permeability was transient, returning to control levels just over one day after the surgery. We also examined inter-strain differences in BSCB permeability using five mouse strains (B10, C57BL/6J, CD-1, A/J and BALB/c) that spanned the range of pain hypersensitivity. We found a significant increase in BSCB permeability in the SNI group that was dependent on strain but that did not correlate with the reported strain differences in PNI-induced tactile hypersensitivity. These results were consistent with a previous experiment using Evans Blue dye to independently assess the status of the BSCB permeability. Conclusions: DCE-MRI provides a sensitive and non-invasive method to follow BSCB permeability in the same group of mice over time. Examining differences between mouse strains, we demonstrated that there is an important genetically-based control of the PNI-induced increase in BSCB permeability and that the critical genetic determinants of BSCB opening after PNI are distinct from those that determine genetic variability in PNI-induced pain hypersensitivity.

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Spinal macrophages resolve nociceptive hypersensitivity after peripheral injury

Jesse K. Niehaus, Bonnie Taylor-Blake, Lipin Loo, Jeremy M. Simon, Mark J. Zylka

Summary: Peripheral nerve injury leads to long-term pro-inflammatory responses in spinal cord glial cells, but the identity of endogenous cells that resolve spinal inflammation has not been determined. Our study demonstrates that MRC1(+) spinal cord macrophages actively restrain glia to limit neuroinflammation and resolve mechanical pain following superficial injury, suggesting that therapeutic modulation of spinal macrophages could promote long-lasting recovery of neuropathic pain.

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