The Inflammatory And Sympathetic Mechanism Of Neuropathic Pain On Dorsal Root Ganglion

BACKGROUND:Inflammatory responses in the lumbar dorsal root ganglion (DRG) play a key role in the development of a variety of pathologic pain states. Systemic administration of a commonly used anti-inflammatory corticosteroid, triamcinolone acetonide (TA), reduces sympathetic sprouting, mechanical pain behavior, cytokine and nerve growth factor production in the DRG, and incidence of spontaneous bursting activity. We hypothesize that the observed effects of systemic TA are primarily due to local effects at the level of the DRG.Many chronic pain conditions including complex regional pain syndrome are exacerbated by sympathetic activity. In animal models, sympathetic fibers sprout into the dorsal root ganglia (DRG) after peripheral nerve injury, forming abnormal connections with sensory neurons. We hypothesize that cutting the grey ramus to the L5 DRG reduces mechanical pain behaviors in the SNL model.METHODS:Male Sprague-Dawley rats were used for all experiments. Rats were randomly divided into 4 groups:SNL (tight ligation of spinal nerves), SNL+TA, Normal+TA, and Normal. In normal rats (Normal+TA) and in SNL rats (SNL+TA), a single dose of 20?1 TA injectable suspension (10mg/ml) was slowly injected onto the surface of DRG and and surrounding region at the time of SNL or sham surgery. Cutaneous sensitivity to mechanical stimulation was tested on postoperative days 1,3,5, and 7. Immunohistochemical staining was performed to examine tyrosine hydroxylase (TH), glial fibrillary acidic protein (GFAP) and nerve growth factor (NGF) in DRG, and CD11B antibody (OX-42) in spinal cord.Male Sprague-Dawley rats received a unilateral ligation of the ventral ramus of the L5 spinal nerve following the original description by Kim and Chung. In some experiments, the grey ramus located in close proximity to the DRG was isolated and cut, either at the time of, or three weeks before, the spinal nerve ligation surgery. Immunohistochemical staining was performed to examine tyrosine hydroxylase (TH) in DRG. Cutaneous sensitivity to mechanical stimulation was tested.RESULTS:Local TA treatment attenuated mechanical sensitivity, reduced sympathetic sprouting in the DRG, and decreased satellite glia activation, NGF expression level in the DRG and microglia activation in the spinal cord after SNL. Cutting the grey ramus to the L5 DRG reduces mechanical sensitivity in the SNL model.CONCLUSION:This study demonstrates that a single injection of in the vicinity of the axotomized DRG can mimic many of the effects of systemic TA in mitigating the behavioral and cellular abnormalities induced by spinal nerve ligation. This provides a further rational basis for the clinical use of localized steroid injections in some clinical conditions, and provides further support for the idea that localized inflammation at the level of the DRG is an important component of the spinal nerve ligation model even though this is commonly classified as neuropathic pain model. And the study provides further evidence of a correlation between pain behaviors and activation of glia in the DRG and spinal cord. This study demonstrates that a single injection of in the vicinity of the axotomized DRG can decrease NGF expression level in the DRG and likely one of mechanisms of local TA treatment attenuate mechanical sensitivity. This is consistent with the result that TA can reduce sympathetic sprouting and decrease satellite glia activation. And provides further theory basis of corticosteroid clinical application for pain treatment.This study presented evidence that the dorsal ramus of the spinal nerve is a source of sympathetic fibers that sprout into the DRG during early phases of the commonly used spinal nerve ligation model. Pre-cutting the grey ramus to the L5 DRG, a much less invasive procedure than surgical or chemical sympathectomy, markedly reduces the mechanical pain induced by spinal nerve ligation. More relevant to clinical situations, cutting the grey ramus also reduced mechanical pain (albeit with a delay) when done at the time of spinal nerve ligation.