Expression profiling of spinal cord dorsal horn in a rat model of complex regional pain syndrome type-I uncovers potential mechanisms mediating pain and neuroinflammation responses

Ruixiang Chen,Jianqiao Fang,Chengyu Yin,Yuanyuan Li,Boyu Liu,Boyi Liu,Qimiao Hu,Yan Tai,Xiaoli Zheng

doi:10.1186/s12974-020-01834-0

Abstract

BackgroundComplex regional pain syndrome type-I (CRPS-I) is a progressive and devastating pain condition. The mechanisms of CRPS-I still remain poorly understood. We aim to explore expression profiles of genes relevant to pain and neuroinflammation mechanisms involved in CRPS-I.MethodsThe rat chronic post-ischemic pain (CPIP) model that mimics human CRPS-I was established. RNA-sequencing (RNA-Seq), qPCR, Western blot, immunostaining, and pharmacological studies were used for profiling gene changes in ipsilateral spinal cord dorsal horn (SCDH) of CPIP model rat and further validation.ResultsCPIP rats developed persistent mechanical allodynia in bilateral hind paws, accompanied with obvious glial activation in SCDH. RNA-Seq identified a total of 435 differentially expressed genes (DEGs) in ipsilateral SCDH of CPIP rats. qPCR confirmed the expression of several representative genes. Functional analysis of DEGs identified that the most significantly enriched biological processes of upregulated genes include inflammatory and innate immune response. We further identified NLRP3 inflammasome expression to be significantly upregulated in SCDH of CPIP rats. Pharmacological blocking NLRP3 inflammasome reduced IL-1β overproduction, glial activation in SCDH as well as mechanical allodynia of CPIP rats.ConclusionOur study revealed that immune and inflammatory responses are predominant biological events in SCDH of CPIP rats. We further identified NLRP3 inflammasome in SCDH as a key contributor to the pain and inflammation responses in CPIP rats. Thus, our study provided putative novel targets that may help to develop effective therapeutics against CRPS-I.

Highlights

Complex regional pain syndrome type-I (CRPS-I) is a progressive and devastating neuropathic pain condition that usually affects the limb and is not accompanied with a clinically verifiable nerve injury [1]
By analyzing the RNA-Seq dataset, we further identified NLRP3 inflammasome in spinal cord dorsal horn (SCDH) is a key player in mediating the pain and inflammation responses in chronic post-ischemic pain (CPIP) model rats
CPIP model rats showed persistent mechanical allodynia and glial activation in the spinal cord dorsal horn We first established the rat model of CPIP to mimic human CRPS-I according to methods described before [9]

Summary

Introduction

Complex regional pain syndrome type-I (CRPS-I) is a progressive and devastating neuropathic pain condition that usually affects the limb and is not accompanied with a clinically verifiable nerve injury [1]. CRPS-I usually develops after an initial injury, which includes ischemia, soft tissue trauma, surgery, or fractures to the extremity [2, 3]. There are currently no specific drugs approved for the treatment of CRPS. Conventional treatments for CRPS-I include physiotherapy, sympathetic blockade, corticosteroids, and non-steroidal anti-inflammatory drugs (NSAIDs) [5]. None of the above treatment options produce satisfactory relieving effects on CRPS-I, which makes it one of the most clinically challenging neuropathic pain conditions [6]. Complex regional pain syndrome type-I (CRPS-I) is a progressive and devastating pain condition. We aim to explore expression profiles of genes relevant to pain and neuroinflammation mechanisms involved in CRPS-I

Objectives

Methods

Results

Discussion

Conclusion