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Updated: Aug 2, 2026
A Mouse Model of Lumbar Spine Instability
Published on: April 23, 2021
Persistent expression of NLRP3 in spinal microglia promotes development of lumbar disc degeneration
1Department of Orthopaedics, XinHua Hospital Affiliated to Shanghai Jiao Tong University School of Medicine, Shanghai, China.
Introduction:
Activated microglia play a critical role in the development of lumbar disc degeneration (LDD), which is a severe disease that causes neuropathic pain in affected people. Interleukin 1β (IL-1β) is a proinflammatory cytokine produced and secreted by activated microglia to induce the inflammation and the subsequent degradation of the disease discs. Recent findings suggest that activation of IL-1β in cells usually requires the involvement of NACHT, LRR and PYD domains-containing protein 3 (NLRP3)-induced formation of inflammasome. However, the importance of NLRP3 in spinal microglia in LDD is not known and thus addressed in the current study.
Methods:
NLRP3 expression was examined in the spinal discs. Correlation of NLRP3 levels in microglia with the pain score of the LDD patients or Thompson classification of the degeneration level of the patients was determined. The effects of persistent expression or depletion of NLRP3 on phagocytosis potential and production of proinflammatory cytokines in microglia were tested in vitro, while their effects on the severity of LDD and LDD-associated neuropathic pain were assessed in a mouse model for LDD.
Results:
NLRP3 was exclusively expressed in microglia in the spinal discs. NLRP3 levels in microglia strongly correlated with the pain score of the LDD patients, and modestly correlated with the Thompson classification of the degeneration level of the patients. Persistent NLRP3 expression in microglia increased both their phagocytosis potential and production of proinflammatory cytokines, while NLRP3-depleted microglia decreased both their phagocytosis potential and production of proinflammatory cytokines. In a mouse model for LDD, persistent NLRP3 activation in microglia significantly increased the severity of LDD and LDD-associated neuropathic pain, while specific depletion of NLRP3 in microglia significantly attenuated the severity of LDD and reduced the LDD-associated neuropathic pain.
Conclusions:
Persistent activation of NLRP3 in spinal microglia promotes development of LDD, while suppression of NLRP3 in microglia could be a promising strategy for LDD therapy.
Insights
Persistent activation of NACHT, LRR and PYD domains-containing protein 3 (NLRP3) in spinal microglia promotes lumbar disc degeneration (LDD) and associated pain. Suppressing NLRP3 in microglia may offer a promising therapeutic strategy for LDD.
Area of Science:
- Neuroscience
- Immunology
- Orthopedics
Background:
- Activated microglia contribute to lumbar disc degeneration (LDD) and neuropathic pain.
- Interleukin 1β (IL-1β) secreted by microglia drives inflammation and disc degradation.
- NLRP3 inflammasome activation is implicated in IL-1β production.
Purpose of the Study:
- To investigate the role of NLRP3 in spinal microglia in the context of LDD.
- To determine the correlation between NLRP3 levels and LDD severity and pain.
- To assess the therapeutic potential of targeting NLRP3 in LDD.
Main Methods:
- Examined NLRP3 expression in spinal discs and correlated levels with patient pain scores and degeneration.
- Investigated the in vitro effects of NLRP3 modulation on microglial phagocytosis and cytokine production.
- Assessed the in vivo effects of NLRP3 modulation on LDD severity and neuropathic pain in a mouse model.
Main Results:
- NLRP3 was exclusively found in spinal microglia and its levels correlated with LDD pain and degeneration.
- Persistent NLRP3 expression enhanced microglial phagocytosis and pro-inflammatory cytokine production.
- NLRP3 depletion attenuated LDD severity and associated neuropathic pain in a mouse model.
Conclusions:
- Persistent NLRP3 activation in spinal microglia exacerbates LDD development and pain.
- Targeting NLRP3 in microglia presents a potential therapeutic avenue for LDD treatment.
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