<p>DNA Microarray Analysis of Differential Gene Expression in the Dorsal Root Ganglia of Four Different Neuropathic Pain Mouse Models</p>

Abstract

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 wildtype mice. In addition, V1a knockout mice showed similar pain behaviors after SNI to wildtype 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.

Transcriptomic and proteomic profiling of NaV1.8-expressing mouse nociceptors

“…Many studies have focused on investigating pain-associated gene expression changes in DRG. Microarray profiling and RNA-Seq have been widely employed to investigate the DRG transcriptome in many species such as mouse, rat, primate, and human (Chiu et al, 2014 ; Gong et al, 2016 ; Li et al, 2016 ; Barry et al, 2018 ; Ray et al, 2018 ; Megat et al, 2019a , b ; Yokoyama et al, 2020 ; Kupari et al, 2021 ). Among these reports, some assessed mRNA levels specifically in Na V 1.8-expressing (Na V 1.8 + ) nociceptors.…”

Research Hotspots and Trends of Peripheral Nerve Injuries Based on Web of Science From 2017 to 2021: A Bibliometric Analysis

“…Notably, neuropathic pain is one of the chronic pains which is often triggered by PNI and caused by damage to the somatosensory nervous system, with common clinical features such as mechanical allodynia. Neuropathic pain is challenging to cure, and there is currently no known cure ( 51 , 52 ). DRG is widely recognized as a potential target for the treatment of chronic pain due to its ability to transmit harmful stimulus information to the cerebral cortex ( 53 , 54 ).…”

Upregulation of the hypothalamo-neurohypophysial system and activation of vasopressin neurones attenuates hyperalgesia in a neuropathic pain model rat

“…In the peripheral nervous system, a previous study showed that AVP upregulates the function of GABA A in dorsal root ganglion neurones 39 . Furthermore, DNA microarray analysis revealed that the V1a receptor was upregulated in a mouse model of NP 40 . Subcutaneous plantar injection of AVP was shown to attenuate formalin-induced nociceptive pain via peripheral V1a receptors 6 .…”