Long Non-coding RNA Uc.48+ Small Interfering RNA Alleviates Neuroinflammatory Hyperalgesia in Gp120-Treated Rats via the P2Y12 Receptor.

Lichao Peng,Chunping Zhang,Bing Wu,Xiumei Xu,Runan Yang,Guilin Li,Shangdong Liang,Liran Shi,Lifang Zou,Lin Li,Shuangmei Liu

doi:10.3389/fnins.2021.663962

Abstract

Human immunodeficiency virus envelope glycoprotein 120 (gp120) leads to hyperalgesia. Long non-coding RNAs are characterized by the lack of a protein-coding sequence and may contribute to the development and maintenance of inflammatory and neuroinflammatory pain. Rats with neuroinflammatory pain were established by gp120 treatment, which is featured by intensified pain behaviors. Long non-coding RNA uc.48+ was increased in the dorsal root ganglia of gp120-treated rats, and small interfering RNA that targets uc.48+ markedly alleviated hyperalgesia in gp120-treated rats. Notably, uc.48+ overexpression increased P2Y12 expression in control rats dorsal root ganglia and induced hyperalgesia. Uc.48+ small interfering RNA inhibited P2Y12 expression in gp120-treated rats. Uc.48+ potentiated P2Y12 receptor functions in the neurons and heterologous cells. Therefore, uc.48+ siRNA treatment reduced the upregulation of P2Y12 expression and function in DRG neurons, and, hence, alleviated hyperalgesia in gp120-treated rats.

Highlights

Neuropathic and inflammatory pain due to human immunodeficiency virus (HIV) is a major symptom influencing almost 30% of infected patients, causing considerable societal and health burdens (Simpson et al, 2006; Hao, 2013; Schutz and Robinson-Papp, 2013)
Because analgesics for the treatment of HIVassociated neuroinflammatory pain are unavailable, we explore the role of Long non-coding RNAs (lncRNAs) uc.48+ in P2Y12 receptor-mediated HIVassociated neuroinflammatory pain, which may formulate a new therapeutic approach for alleviating HIV-associated neuroinflammatory pain
Our data suggest that the upregulation of uc.48+ expression may be involved in the pathological process of HIV gp120-induced neuroinflammatory pain

Summary

Introduction

Neuropathic and inflammatory pain due to human immunodeficiency virus (HIV) is a major symptom influencing almost 30% of infected patients, causing considerable societal and health burdens (Simpson et al, 2006; Hao, 2013; Schutz and Robinson-Papp, 2013). HIV-1 envelope glycoprotein 120 (gp120) causes the release of interleukin-1β and tumor necrosis factor-alpha (Jones et al, 2005). The dorsal root ganglia (DRG) contain pseudounipolar neurons and primary afferent fibers that transmit noxious stimuli from the periphery to the central nervous system (Basbaum et al, 2009; Shi et al, 2018). Evidence suggests that gp120 can injure the primary sensory neurons (Meucci et al, 1998; Keswani et al, 2003; Chi et al, 2011; Mangus et al, 2014). In vivo studies have found that gp120 application into the rat sciatic nerves will produce hyperalgesia, and patients with HIV

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