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Updated: Aug 9, 2026
Identifying Microglia and Peripheral Infiltrating Macrophages in the Injured Spinal Cords Using Flow Cytometry
Published on: June 24, 2025
Role of spinal microglia in rat models of peripheral nerve injury and inflammation
Anna K Clark1, Clive Gentry, Elizabeth J Bradbury
1Neurorestoration, Wolfson Centre for Age Related Diseases, King's College London, Wolfson Wing, Hodgkin Building, Guys Campus, London SE1 1UL, UK.
Abstract:
Mounting evidence supports the hypothesis that spinal microglia modulate the development and maintenance of some chronic pain states. Here we examined the role of spinal microglia following both peripheral inflammatory insult and peripheral nerve injury. We observed significant ipsilateral dorsal horn microglia activation 2 weeks after injury and bilateral activation 50 days following nerve injury as well as 24 h following intraplantar zymosan but not intraplantar complete Freund's adjuvant (CFA). Ipsilateral but not contralateral microglia activation was associated with hind paw mechanical hyperalgesia. Spinal injection of the glial metabolic inactivator fluorocitrate attenuated ipsilateral hyperalgesia and bilateral spinal microglia activation after peripheral nerve injury. Intrathecal fluorocitrate reversed hyperalgesia after intraplantar zymosan and produced no reversal of CFA-induced hyperalgesia. These data suggest a role for spinal glia in the persistence of mechanical hyperalgesia following peripheral nerve injury. However, activation of spinal microglia contralaterally did not correlate to nociception. Furthermore, it would appear that the time course of microglia activation and their contribution to inflammatory pain is dependent on the inflammatory stimulus administered.
Insights
Spinal microglia activation contributes to chronic pain after nerve injury. Inhibiting glial metabolism reduces this pain, suggesting microglia as a therapeutic target for neuropathic pain.
Area of Science:
- Neuroscience
- Immunology
- Pain Research
Background:
- Spinal microglia are increasingly recognized for their role in chronic pain.
- Their specific involvement in different pain states requires further elucidation.
Purpose of the Study:
- To investigate the role of spinal microglia in chronic pain following peripheral nerve injury and inflammatory insults.
- To determine the correlation between microglia activation and hyperalgesia.
Main Methods:
- Induction of peripheral nerve injury and inflammatory insults (zymosan, CFA) in animal models.
- Assessment of microglia activation in the spinal cord using immunohistochemistry.
- Evaluation of hind paw mechanical hyperalgesia.
- Administration of fluorocitrate, a glial metabolic inactivator, intrathecally.
Main Results:
- Significant ipsilateral spinal microglia activation observed after nerve injury and zymosan-induced inflammation, correlating with mechanical hyperalgesia.
- Bilateral microglia activation occurred later after nerve injury.
- Fluorocitrate treatment attenuated hyperalgesia and microglia activation following nerve injury and zymosan, but not CFA.
- Contralateral microglia activation did not correlate with nociception.
Conclusions:
- Spinal microglia play a role in the persistence of mechanical hyperalgesia after peripheral nerve injury.
- The contribution of spinal microglia to inflammatory pain is stimulus-dependent.
- Targeting glial metabolism may offer a therapeutic strategy for neuropathic pain.
