Suppression of microglial Ccl2 reduces neuropathic pain associated with chronic spinal compression

Frontiers in Immunology, 2023 · DOI: 10.3389/fimmu.2023.1191188 · Published: July 11, 2023

Simple Explanation

Chronic spinal compression, a common complication of spinal cord injury (SCI), often leads to neuropathic pain linked to microglia activation. This study explores whether modifying chemokine (C-C motif) ligand 2 (Ccl2) levels in microglia can alleviate neuropathic pain from chronic spinal compression. The study used a rat SCI model to identify Ccl2 as a primary gene altered in microglia. Elevated microglial Ccl2 levels were found in disc specimens from SCI patients with chronic spinal compression, correlating with degeneration and pain scores. In vivo depletion of Ccl2 in microglia mitigated chronic spinal compression and related pain in mice, likely due to changes in pain-associated cytokines. Targeting Ccl2 in microglia could potentially treat chronic spinal compression and SCI-associated pain.

Study Duration

Analyzed at 24 weeks of age

Participants

30 healthy donors, 30 SCI patients, male mice in 4 experimental groups of 5 each

Evidence Level

Original Research

Key Findings

1
Ccl2 was identified as the primary gene altered in microglia within a rat SCI model.
2
Microglial Ccl2 levels were significantly elevated in disc specimens from SCI patients diagnosed with chronic spinal compression and strongly correlated with the Thompson classification of the degeneration level and pain score.
3
In vivo depletion of Ccl2 in microglia mitigated the severity of chronic spinal compression and related pain in ttw mice, likely due to significant changes in pain-associated cytokines and factors.

Research Summary

This study investigates the role of microglial Ccl2 in neuropathic pain associated with chronic spinal compression. It identifies Ccl2 as a key gene upregulated in microglia after SCI and demonstrates a positive correlation between microglial Ccl2 levels and the severity of spinal compression and pain in SCI patients. The researchers developed adeno-associated viruses (AAVs) to specifically target microglia and deplete Ccl2. In vitro experiments showed that Ccl2 depletion induced a shift from a pro-inflammatory to an anti-inflammatory phenotype in microglia. In vivo experiments using a mouse model of chronic spinal compression (ttw mice) showed that depletion of Ccl2 in microglia reduced the severity of spinal compression and associated pain. This effect was linked to changes in pain-associated cytokines and factors in the spine.

Practical Implications

Therapeutic Target

Microglial Ccl2 is a potential therapeutic target for treating chronic spinal compression and SCI-associated pain.

Treatment Avenue

Therapeutically targeting Ccl2 in microglia could offer a potential avenue for treating chronic spinal compression and SCI-associated pain.

Pro- to Anti-inflammatory Shift

Depletion of Ccl2 in microglia resulted in a proinﬂammatory to anti-inﬂammatory phenotypic adaptation, suggesting a mechanism for pain reduction.

Study Limitations

1
The condition can also occur in individuals without a history of SCI
2
The use of a single mouse model may restrict the generalizability of the ﬁndings.
3
This study only examined the effects of Ccl2 depletion in microglia

Your Feedback

Was this summary helpful?

Back to Spinal Cord Injury