Multimodal assessment of nervous and immune system responses following sciatic nerve injury

Abstract

Subsequent to peripheral nerve compression and irritation, pathophysiological processes take place within nervous and immune systems. Here, we utilized a multimodal approach to comprehend peripheral and central soft tissue changes as well as alterations occurring in systemic analytes following unilateral chronic constriction injury (CCI) of the sciatic nerve in rodents. Using magnetic resonance imaging and [18F]-2-fluoro-2-deoxy-d-glucose (FDG) positron emission tomography, we demonstrated robust structural abnormalities and enhanced FDG uptake within the injured nerve and surrounding muscle, respectively. To assess whether central morphological changes were induced by nerve injury, diffusion tenor imaging was performed. A decrease in fractional anisotropy in primary motor cortex contralateral to the injury site was observed. Evaluation of a panel of circulating cytokines, chemokines, and growth factors showed decreased levels of interleukin-1β and Fractalkine in CCI animals. Area under the receiver operating curve (ROC) calculations of analyte levels, imaging, and behavioral end points ranged from 0.786 to 1, where behavioral and peripheral imaging end points (eg, FDG uptake in muscle) were observed to have the highest discriminatory capabilities (maximum area under ROC = 1) between nerve injury and sham conditions. Lastly, performance of correlation analysis involving all analyte, behavioral, and imaging data provided an understanding of the overall association amongst these end points, and importantly, a distinction in correlation patterns was observed between CCI and sham conditions. These findings demonstrate the multidimensional pathophysiology of sciatic nerve injury and how a combined analyte, behavioral, and imaging assessment can be implemented to probe this complexity.

Chronic sciatic nerve compression induces fibrosis in dorsal root ganglia

“…A previous study examined injured nerves and surrounding muscles using magnetic resonance imaging, and found structural abnormalities ( 26 ). In addition, enhanced FDG uptake was detected in these area using (18F)-2-fluoro-2-deoxy-d-glucose positron emission tomography ( 26 ). Therefore, the present study investigated the molecular mechanism involved in chronic sciatic nerve compression-induced DRG damage and muscle fibrosis 3 weeks following surgery.…”

Completing the Pain Circuit: Recent Advances in Imaging Pain and Inflammation beyond the Central Nervous System

“…An excellent example of such an approach is determining the relationship between carpal tunnel nerve conduction velocity and regional gray matter alterations in the brain 65. This study found that patients with carpal tunnel syndrome had significant gray matter reductions in the hand area of the somatosensory cortex, a reduction that was correlated to lower median nerve conduction velocity.…”

A critical evaluation of validity and utility of translational imaging in pain and analgesia: Utilizing functional imaging to enhance the process

“…Despite this limitation, recent results stemming from imaging muscle and nerve in preclinical, neuropathic conditions could be utilized to further hypothesize how peripheral abnormalities track with central function and structure as well as other markers (i.e., pain-like behaviors or soluble biomarkers). For example, using a combination of T1 or T2-weighted structural MRI along with 18 F-FDG PET/CT, Lasko et al and Biswal and colleagues independently demonstrated robust unilateral edema and enhanced glucose metabolism proximal to the nerve injury site, in distal nerve and in distal muscle within the SNI and CCI models, respectively (Behera et al, 2011; Lasko et al, 2013). It should be kept in mind that unilateral nerve injury can have widespread modulatory effects on the peripheral nervous system as suggested by bilateral increases of calcium flux in sciatic nerves (Behera et al, 2013).…”