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Partial Sciatic Nerve Ligation: A Mouse Model of Chronic Neuropathic Pain to Study the Antinociceptive Effect of Novel Therapies
Published on: October 6, 2022
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Sigma-1 Receptors Control Neuropathic Pain and Peripheral Neuroinflammation After Nerve Injury in Female Mice: A
M Carmen Ruiz-Cantero1,2,3, José M Entrena2,3,4, Antonia Artacho-Cordón1,2,3
1Department of Pharmacology, Faculty of Medicine, University of Granada, Granada, 18016, Spain.
Summary
Sigma-1 receptor inhibition reduces neuropathic pain by decreasing neuroinflammation in the dorsal root ganglia. This involves reducing immune cell recruitment, particularly macrophages and CD4+ T cells, after nerve injury.
Area of Science:
- Neuroscience
- Immunology
- Pharmacology
Background:
- Neuropathic pain mechanisms involving sigma-1 receptors are not fully understood.
- Sigma-1 receptor inhibition shows potential for pain amelioration.
Purpose of the Study:
- To investigate the genome-wide transcriptomic changes in dorsal root ganglia (DRG) following nerve injury in wild-type and sigma-1 receptor knockout mice.
- To elucidate the role of sigma-1 receptors in neuroinflammation and neuropathic pain.
Main Methods:
- Genome-wide transcriptomic analysis (RNAseq) of DRG.
- Flow cytometry to assess immune cell populations.
- Behavioral testing for neuropathic pain (mechanical and cold allodynia, spontaneous pain).
- Pharmacological intervention with a CCR5 antagonist (maraviroc).
Main Results:
- Spared Nerve Injury (SNI) in wild-type mice induced significant immune-related transcriptomic changes in DRG.
- Sigma-1 receptor knockout attenuated immune cell (macrophage/monocyte, CD4+ T cell) recruitment to the DRG post-SNI.
- Sigma-1 knockout mice exhibited reduced neuropathic pain behaviors.
- CCR5 antagonist treatment partially mimicked knockout effects on pain, suggesting CD4+ T cell involvement.
Conclusions:
- Sigma-1 receptor inhibition decreases DRG neuroinflammation following nerve injury.
- Reduced immune cell infiltration contributes to the anti-neuropathic effects of sigma-1 receptor inhibition.
- Modulation of peripheral CD4+ T cells may partially explain pain reduction, particularly for spontaneous and mechanical pain.
