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Updated: Jun 27, 2026
Rat Model of Widespread Cerebral Cortical Demyelination Induced by an Intracerebral Injection of Pro-Inflammatory Cytokines
Published on: September 21, 2021
Role of spinal microglia in myositis-induced central sensitisation: an immunohistochemical and behavioural study in
Marucia Chacur1, Daniela Lambertz, Ulrich Hoheisel
1Institute of Anatomy and Cell Biology, University of Heidelberg, Im Neuenheimer Feld 307, Heidelberg, Germany.
Abstract:
There is increasing evidence that spinal glial cells play an important role in chronic pain states. However, so far no data on the role of microglia in muscle pain are available. The aim of the present study was to investigate the involvement of spinal microglial cells in chronic muscle pain. In a rat model of chronic muscle inflammation (injection of complete Freund s adjuvant into the gastrocnemius-soleus muscle) alterations of microglia were visualized with quantitative OX-42 immunohistochemistry in the dorsal horn of the segments L4 and L5 12 days after induction of inflammation. In behavioural experiments the influence of chronic intrathecally applied minocycline - a specific microglia inhibitor - or an antibody against tumour necrosis factor-alpha (TNF-alpha; a cytokine released from microglia) on pain-related behaviour was investigated after 1, 3, 6, and 12 days. The immunhistochemical data show that in the deep laminae of the spinal dorsal horn microglial cells reacted with morphological changes to the muscle inflammation. Following inflammation, the mean boundary length surrounding the OX-42 immunostained area was significantly shorter. This indicates that microglial cells were activated by the myositis and withdrew their processes. Chronic intrathecal administration of minocycline or anti TNF-alpha with an osmotic mini-pump largely normalised the inflammation-induced changes in spontaneous exploratory behaviour and attenuated the hypersensitivity to mechanical stimulation. Both the immunohistochemical and behavioural data show that spinal microglial cells are involved in nociceptive processes in the cause of a chronic muscle inflammation.
Insights
Spinal microglial cells are activated during chronic muscle inflammation, contributing to pain. Inhibiting these cells or their released tumor necrosis factor-alpha (TNF-alpha) reduced pain behaviors in rats.
Area of Science:
- Neuroscience
- Immunology
- Pain Research
Background:
- Spinal glial cells, particularly microglia, are implicated in chronic pain.
- Limited data exists on microglia's role in muscle pain.
- Chronic muscle inflammation is a significant source of pain.
Purpose of the Study:
- To investigate the involvement of spinal microglial cells in chronic muscle pain.
- To explore the therapeutic potential of targeting microglia in muscle pain models.
Main Methods:
- A rat model of chronic muscle inflammation induced by complete Freund's adjuvant injection.
- Quantitative OX-42 immunohistochemistry to visualize microglial activation in the spinal dorsal horn.
- Behavioral assessments of pain-related behaviors following intrathecal administration of minocycline (microglia inhibitor) or anti-TNF-alpha antibody.
Main Results:
- Muscle inflammation led to morphological changes in spinal microglial cells, indicating activation.
- Intrathecal minocycline or anti-TNF-alpha treatment normalized exploratory behavior and reduced mechanical hypersensitivity.
- These interventions attenuated inflammation-induced changes in pain-related behaviors.
Conclusions:
- Spinal microglial cells are activated in response to chronic muscle inflammation.
- Microglia play a significant role in the development and maintenance of muscle pain.
- Targeting spinal microglia or TNF-alpha offers a potential therapeutic strategy for chronic muscle pain.
