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

Molecular Pain

R Mark Henkelman⁴  Michael W Salter¹  Catherine D Jones²  Robert E Sorge²  Jeffrey S Mogil³  Brian J Nieman⁴  Jonathan Bishop⁴  Xue Jun Liu¹  Christine L Laliberté⁴  Lindsay S Cahill⁴ 

[1] Program in Neurosciences and Mental Health, The Hospital for Sick Children, Toronto, Ontario, Canada;Department of Psychology, University of Alabama, Birmingham, Alabama, USA;Alan Edwards Centre for Research on Pain, McGill University, Montreal, Quebec, Canada;Mouse Imaging Centre, Hospital for Sick Children, 25 Orde Street, Toronto, Ontario, Canada

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

Others  :  1138495
DOI  :  10.1186/1744-8069-10-60

 received in 2014-05-11, accepted in 2014-09-10,  发布年份 2014

【 摘 要 】

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.

【 授权许可】

   
2014 Cahill et al.; licensee BioMed Central Ltd.

【 图 表 】

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