miR‑3120/Hsc70 participates in forced swim stress‑induced mechanical hyperalgesia in rats in an inflammatory state

Xu,Shiqin; Liu,Shijiang; Yang,Juan; Li,Renqi; Mao,Mao; Feng,Shanwu; Wang,Xian

doi:10.3892/mmr.2023.13126

miR‑3120/Hsc70 participates in forced swim stress‑induced mechanical hyperalgesia in rats in an inflammatory state

Authors:
- Shiqin Xu
- Shijiang Liu
- Juan Yang
- Renqi Li
- Mao Mao
- Shanwu Feng
- Xian Wang
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Affiliations: Department of Anesthesiology and Pain Medicine, Women's Hospital of Nanjing Medical University, Nanjing Maternity and Child Health Care Hospital, Nanjing, Jiangsu 210004, P.R. China, Department of Anesthesiology and Perioperative Medicine, The First Affiliated Hospital of Nanjing Medical University, Nanjing, Jiangsu 210004, P.R. China, Department of Anesthesiology and Pain Medicine, Women's Hospital of Nanjing Medical University, Nanjing Maternity and Child Health Care Hospital, Nanjing, Jiangsu 210004, P.R. China
Published online on: November 8, 2023 https://doi.org/10.3892/mmr.2023.13126
Article Number: 3
Copyright: © Xu et al. This is an open access article distributed under the terms of Creative Commons Attribution License.

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Abstract

The heat shock cognate 71 kDa protein (Hsc70) is a stress‑inducible ATPase that can protect cells against harmful stimuli. Transient receptor potential vanilloid 1 (TRPV1) is a well‑documented nociceptor. Notably, Hsc70 can inhibit TRPV1 expression and function, suggesting that Hsc70 may have pain regulation potential. However, the role of Hsc70 in stress‑induced hyperalgesia remains unclear. In the present study, the participation of Hsc70 and its regulator microRNA (miR)‑3120 were investigated in forced swim (FS) stress‑induced mechanical hyperalgesia in rats in an inflammatory state. Complete Freund's adjuvant (CFA) hind paw injection was performed to induce inflammatory pain in rats (CFA rats). Furthermore, in FS + CFA rats, FS stress was performed for 3 days before CFA injection. The levels of Hsc70, miR‑3120 and their downstream molecule TRPV1 were measured in the dorsal root ganglion (DRG) with western blotting, immunofluorescence, reverse transcription‑quantitative polymerase chain reaction and fluorescence in situ hybridization. The results revealed that FS stress significantly exacerbated CFA‑induced mechanical pain. Furthermore, CFA upregulated Hsc70 and TRPV1 expression, which was partially inhibited or further enhanced by FS stress, respectively. In FS + CFA rats, intrathecal injection of a lentiviral vector overexpressing Hsc70 (LV‑Hsc70) could decrease TRPV1 expression and improve the mechanical pain. Additionally, the expression levels of miR‑3120, a regulator of Hsc70, were markedly upregulated on day 3 following FS stress. Finally, miR‑3120 was identified to be colocalized with Hsc70 and expressed in all sizes of DRG neurons. In CFA rats, DRG injection of miR‑3120 agomir to induce overexpression of miR‑3120 resulted in similar TRPV1 expression and behavioral changes as those caused by FS stress, which were abolished in the presence of LV‑Hsc70. These findings suggested that miR‑3120/Hsc70 may participate in FS stress‑induced mechanical hyperalgesia in rats in an inflammatory state, possibly via disinhibiting TRPV1 expression in the DRG neurons.

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