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Secreted frizzled‐related protein 1 regulates the progression of neuropathic pain in mice following spinal nerve ligation.
- Source :
-
Journal of Cellular Physiology . Aug2018, Vol. 233 Issue 8, p5815-5822. 8p. - Publication Year :
- 2018
-
Abstract
- Previous studies have shown that the Wnt/β‐catenin signaling pathway plays an important role in modulating neuropathic pain after sciatic nerve injury. In this study, we explored the role of secreted frizzled‐related protein 1 (SFRP1), a Wnt antagonist, in neuropathic pain using a mouse model following spinal nerve ligation (SNL). We found SNL‐induced SFRP1 downregulation in the spinal cord. Further, overexpression of SFRP1 via spinal injection into the spinal cord attenuated SNL‐induced allodynia, hyperalgesia, and neuroinflammation. Consistently, in vitro assays also showed decreased expression of SFRP1 in spinal cord astrocytes after exposure to lipopolysaccharide (LPS). Overexpression of SFRP1 significantly alleviated the secretion of LPS‐induced proinflammatory factors in spinal cord astrocytes. Furthermore, spinal injection of LPS‐treated astrocytes induced allodynia and hyperalgesia, which were reversed by the overexpression of SFRP1 in these cells. Additionally, SNL increased Wnt3a and β‐catenin levels and also induced an increase in nuclear expression of β‐catenin; these effects were all attenuated by SFRP1. Finally, we found that downregulation of SFRP1, mainly through DNA methylation, is involved in the pathogenesis of neuropathic pain. Taken together, these results suggested that the SFRP1/Wnt3a/β‐catenin signaling pathway might be a suitable therapeutic target for neuropathic pain. [ABSTRACT FROM AUTHOR]
Details
- Language :
- English
- ISSN :
- 00219541
- Volume :
- 233
- Issue :
- 8
- Database :
- Academic Search Index
- Journal :
- Journal of Cellular Physiology
- Publication Type :
- Academic Journal
- Accession number :
- 129280752
- Full Text :
- https://doi.org/10.1002/jcp.26358