학술논문

DNA Microarray Analysis of Differential Gene Expression in the Dorsal Root Ganglia of Four Different Neuropathic Pain Mouse Models
Document Type
Report
Source
Journal of Pain Research. November 30, 2020, Vol. 13, p3031, 13 p.
Subject
United States
Japan
Language
English
ISSN
1178-7090
Abstract
Purpose: Pathological stimuli or injury to the peripheral nervous system can trigger neuropathic pain with common clinical features such as allodynia and hypersensitivity. Although various studies have identified molecules or genes related to neuropathic pain, the essential components are still unclear. Therefore, in this study, we investigated the molecular and genetic factors related to neuropathic pain. Methods: We extracted candidate genes in the dorsal root ganglion (DRG) from three nerve injury mouse models and a sham-operated model (sciatic nerve ligation and resection, sural nerve resection, spared nerve injury [SNI], and sham) using DNA microarray to elucidate the genes responsible for the neuropathic pain mechanism in the SNI model, which exhibits hypersensitivity in the hindpaw of the preserved sural nerve area. We eliminated as many biases as possible. We then focused on an upregulated endogenous vasopressin receptor and clarified whether it is closely associated with traumatic neuropathic pain using a knockout mouse and drug-mediated suppression of the gene. Results: Algorithm analysis of DNA microarray results identified 50 genes significantly upregulated in the DRG of the SNI model. Two independent genes--cyclin-dependent kinase-1 (CDK-1) and arginine vasopressin receptor 1A (V1a)--were subsequently identified as candidate SNI-specific genes in the DRG by quantitative PCR analysis. Administration of V1a agonist to wild-type SNI mice significantly alleviated neuropathic pain. However, V1a knockout mice did not exhibit higher hypersensitivity to mechanical stimulation than wild-type mice. In addition, V1a knockout mice showed similar pain behaviors after SNI to wild-type mice. Conclusion: Through the DNA microarray analysis of several neuropathic models, we detected specific genes related to chronic pain. In particular, our results suggest that V1a in the DRG may partially contribute to the mechanism of neuropathic pain. Keywords: neuropathic pain, arginine vasopressin 1a, peripheral nerve injury, dorsal root ganglion, microarray, molecular target
Introduction Neuropathic pain is a form of chronic pain caused by conditions affecting the somatosensory nervous system. (1) It is clinically characterized by allodynia (ie, hypersensitivity to nociceptive stimulation). Various [...]