Related Experiment Video
Updated: Mar 3, 2026
Applying Stereotactic Injection Technique to Study Genetic Effects on Animal Behaviors
Published on: May 10, 2015
Spared Nerve Injury Increases the Expression of Microglia M1 Markers in the Prefrontal Cortex of Rats and Provokes
Ning Xu1,2, Xiao-Hui Tang3, Wei Pan3
1Department of Anesthesiology, Zhongda Hospital, School of Medicine, Southeast UniversityNanjing, China.
Abstract:
Pain and depression are frequently co-existent in clinical practice, yet the underlying mechanisms remain largely to be determined. Microglia activation and subsequent pro-inflammatory responses play a crucial role in the development of neuropathic pain and depression. The process of microglia polarization to the pro-inflammatory M1 or anti-inflammatory M2 phenotypes often occurs during neuroinflammation. However, it remains unclear whether M1/M2 microglia polarization is involved in the neuropathic pain induced by spared nerve injury (SNI). In the present study, the mechanical withdrawal threshold, forced swim test, sucrose preference test, and open field test were performed. The levels of microglia markers including ionized calcium-binding adaptor molecule 1 (Iba1), cluster of differentiation 11b (CD11b), M1 markers including CD68, inducible nitric oxide synthase (iNOS), interleukin-1β (IL-1β), IL-6, tumor necrosis factor-a (TNF-α), 8-hydroxy-2-deoxyguanosine (8-OH-dG), and M2 markers including CD206, arginase 1 (Arg1), IL-4 in the prefrontal cortex were determined on day 14 after SNI. The results showed that SNI produced mechanical allodynia and depressive-like behaviors, and also increased the expressions of microglia markers (Iba1, CD11b) and M1 markers (CD68, iNOS, IL-1β, TNF-α, and 8-OH-dG) in the prefrontal cortex. Notably, minocycline administration reversed these abnormalities. In addition, minocycline also promoted M2 microglia polarization as evidenced by up-regulation of CD206 and Arg1. In conclusion, data from our study suggest that SNI can lead to depression-like behaviors, while M1 polarization and consequent overproduction of pro-inflammatory cytokines plays a key role in the pathogenesis of neuropathic pain. The data furthermore indicate that modulation of inflammation by inhibition of M1 polarization could be a strategy for treatment of neuropathic pain, and might prevent the induction of neuropathic pain-induced depression symptoms.
Insights
Spared nerve injury induces neuropathic pain and depression by promoting M1 microglia polarization. Minocycline treatment reversed these effects, suggesting anti-inflammatory strategies may treat pain and depression.
Area of Science:
- Neuroscience
- Immunology
- Pharmacology
Background:
- Neuropathic pain and depression often co-occur, with microglia activation implicated in their development.
- Microglia polarization into M1 (pro-inflammatory) or M2 (anti-inflammatory) phenotypes is key in neuroinflammation.
- The role of M1/M2 microglia polarization in neuropathic pain following spared nerve injury (SNI) is not well understood.
Purpose of the Study:
- To investigate the involvement of M1/M2 microglia polarization in SNI-induced neuropathic pain and depression.
- To evaluate the therapeutic potential of minocycline in modulating microglia polarization and alleviating associated symptoms.
Main Methods:
- Spared nerve injury (SNI) model in rodents.
- Behavioral tests: mechanical withdrawal threshold, forced swim test, sucrose preference test, open field test.
- Analysis of microglia markers (Iba1, CD11b) and M1/M2 markers (CD68, iNOS, IL-1β, TNF-α, 8-OH-dG, CD206, Arg1, IL-4) in the prefrontal cortex.
Main Results:
- SNI induced mechanical allodynia and depressive-like behaviors.
- SNI increased M1 microglia markers (CD68, iNOS, IL-1β, TNF-α, 8-OH-dG) and microglia activation markers (Iba1, CD11b) in the prefrontal cortex.
- Minocycline treatment reversed SNI-induced pain and depression, reduced M1 markers, and promoted M2 polarization (increased CD206, Arg1).
Conclusions:
- SNI induces neuropathic pain and depression, associated with M1 microglia polarization and pro-inflammatory cytokine release.
- Inhibition of M1 polarization and promotion of M2 polarization by minocycline offers a potential therapeutic strategy for neuropathic pain and associated depression.
