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Chronic Post-Ischemia Pain Model for Complex Regional Pain Syndrome Type-I in Rats
Published on: January 21, 2020
MiR-101 promotes pain hypersensitivity in rats with chronic constriction injury via the MKP-1 mediated MAPK pathway
Shuang Qiu1, Benjuan Liu1, Yanshuai Mo1
1Department of Anesthesiology, Linyi People's Hospital, Linyi, China.
Abstract:
This study was performed to characterize the effect of microRNA-101 (miR-101) on the pain hypersensitivity in CCI rat models with the involvement of mitogen-activated protein kinase phosphatase 1 (MKP-1) in spinal cord microglial cells. The mechanical withdrawal threshold (MWT) and thermal withdrawal latency (TWL) in the developed CCI models were determined to assess the hypersensitivity of rats to mechanical stimulation and thermal pain. To assess inflammation, the levels of interleukin (IL)-1β, IL-6 and tumour necrosis factor-α (TNF-α) in the spinal dorsal horns of CCI rats and lipopolysaccharide (LPS)-activated microglial cells were examined. miR-101 and MKP-1 gain- and loss-of-function experiments were conducted in in vivo and in vitro settings to examine the roles of miR-101 and MKP-1 in CCI hypersensitivity and inflammation. The results showed that miR-101 was highly expressed in the spinal dorsal horn and microglial cells of CCI rat models. Furthermore, overexpression of miR-101 promoted the pain hypersensitivity in CCI rat models by reducing MWT and TWL. The overexpression of miR-101 also promoted inflammation in LPS-exposed microglial cells, as indicated by increased levels of IL-1β, IL-6 and TNF-α. MiR-101 was shown to target MKP-1, inhibiting its expression. Moreover, miR-101 promoted pain hypersensitivity in CCI rat models by inhibiting MKP-1 expression and activating the mitogen-activated protein kinase (MAPK) signalling pathway. Taken together, miR-101 could potentially promote hypersensitivity and inflammatory response of microglial cells and aggravate neuropathic pain in CCI rat models by inhibiting MKP-1 in the MAPK signalling pathway.
Insights
MicroRNA-101 (miR-101) exacerbates neuropathic pain and inflammation in rats by inhibiting MKP-1 in microglial cells, activating the MAPK pathway. This finding highlights miR-101 as a potential therapeutic target for pain management.
Area of Science:
- Neuroscience
- Molecular Biology
- Immunology
Background:
- Neuropathic pain, often resulting from chronic constriction injury (CCI), involves complex mechanisms including neuroinflammation.
- Microglial cells in the spinal cord play a crucial role in mediating pain hypersensitivity and inflammatory responses.
- MicroRNAs (miRNAs) are emerging as key regulators in pain pathways, but their specific roles in CCI-induced pain remain under investigation.
Purpose of the Study:
- To investigate the role of microRNA-101 (miR-101) in the development of pain hypersensitivity and neuroinflammation in a rat model of CCI.
- To elucidate the underlying molecular mechanisms involving mitogen-activated protein kinase phosphatase 1 (MKP-1) and the mitogen-activated protein kinase (MAPK) signaling pathway in spinal cord microglial cells.
Main Methods:
- CCI rat models were established to induce neuropathic pain, and mechanical withdrawal threshold (MWT) and thermal withdrawal latency (TWL) were measured.
- Levels of inflammatory cytokines (IL-1β, IL-6, TNF-α) were assessed in spinal dorsal horns and lipopolysaccharide (LPS)-activated microglial cells.
- Gain- and loss-of-function experiments for miR-101 and MKP-1 were performed in vivo and in vitro to determine their functional roles.
Main Results:
- miR-101 expression was significantly upregulated in the spinal dorsal horn and microglial cells of CCI rats.
- Overexpression of miR-101 reduced MWT and TWL, indicating increased pain hypersensitivity, and elevated inflammatory cytokine levels in LPS-treated microglial cells.
- miR-101 directly targeted and inhibited MKP-1 expression, leading to the activation of the MAPK signaling pathway.
Conclusions:
- miR-101 promotes pain hypersensitivity and neuroinflammation in CCI rat models by suppressing MKP-1 expression and activating the MAPK pathway in spinal cord microglial cells.
- These findings suggest that miR-101 plays a critical role in the pathogenesis of neuropathic pain.
- Targeting miR-101 may represent a novel therapeutic strategy for managing neuropathic pain and associated inflammatory responses.
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