Abstract

Patients with complex regional pain syndrome (CRPS) exhibit diverse symptoms, such as neuropathic pain, allodynia, local edema and skin color changes in the affected lesion. Although nerve injury may cause CRPS, pathophysiological mechanisms underlying the syndrome are unclear, and local edema, a characteristic of CRPS, has not been evaluated quantitatively for technical reasons. Here, using a rat spinal nerve ligation-induced CRPS model, we show that edematous changes in gastrocnemius muscle can be detected quantitatively by diffusion magnetic resonance imaging (MRI). Using the line-scan diffusion spectrum on a 1.5 T clinical MR imager, we demonstrate significant elevation of the apparent diffusion coefficient (ADC) ratios in gastrocnemius muscle on the ligated versus the sham-operated rats by one day after surgery, those ratios gradually decreased over time. Meanwhile, T2 ratios in gastrocnemius muscle on the ligated rats increased gradually and significantly, peaking two weeks after surgery, and those ratios remained high and were consistent with edema. Expression of vascular endothelial growth factor (VEGF), a key regulator of blood vessel formation and function, was significantly lower in gastrocnemius muscle on the ligated versus non-ligated side, suggesting that nerve ligation promotes edematous changes and perturbs VEGF expression in target muscle.

Highlights

  • Complex regional pain syndrome (CRPS) is a neuropathic disorder characterized by continuing regional pain, which is incompatible with the usual course of general trauma or other lesions with respect to the time course or degree

  • Rats subjected to spinal nerve ligation develop mechanical allodynia We performed left L5 spinal nerve ligation or sham surgery in nine-week-old female rats and monitored them for development of mechanical allodynia, a characteristic feature of CRPS

  • T2 ratios of gastrocnemius muscle in the ligation group increased gradually, and were significantly high compared to the control group by five days post-surgery (P < 0.05), and significant differences were observed throughout the experimental period (Fig 4)

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Summary

Introduction

Complex regional pain syndrome (CRPS) is a neuropathic disorder characterized by continuing regional pain, which is incompatible with the usual course of general trauma or other lesions with respect to the time course or degree. CRPS shows variable progression over time [1,2,3]. Quantification of edematous changes by diffusion magnetic resonance imaging mechanisms underlying these disorders are unclear, and multiple factors, among them peripheral and central sensitization, inflammation, altered sympathetic and catecholaminergic function, altered somatosensory representation in the brain, genetic factors, and psychophysiological interactions, likely play a role in CRPS development [4]. Our lack of knowledge of the underlying pathophysiology of CRPS has hampered efforts to develop definitive treatment, existing approaches are reportedly more effective when started at an early stage [5]. It is currently difficult to objectively diagnose or evaluate treatment efficacy in CRPS

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