Front Neurosci.2021 Jul 13;15:663962.doi: 10.3389/fnins.2021.663962.eCollection 2021.

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

Lichao Peng  1 Bing Wu  2   3 Liran Shi  2   3 Lifang Zou  2   3 Lin Li  2   3 Runan Yang  2   3 Xiumei Xu  2   3 Guilin Li  2   3 Shuangmei Liu  2   3 Chunping Zhang  3   4 Shangdong Liang  2   3 Affiliations

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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.

Keywords: HIV gp120-associated neuroinflammatory pain; P2Y12 receptor; dorsal root ganglia; long non-coding RNA; small interfering RNA.