Spinal Cord Stimulation Alleviates Neuropathic Pain by Attenuating Microglial Activation via Reducing Colony-Stimulating Factor 1 Levels in the Spinal Cord in a Rat Model of Chronic Constriction Injury

Anesth Analg, 2022 · DOI: 10.1213/ANE.0000000000006016 · Published: July 1, 2022

Simple Explanation

This study investigates how spinal cord stimulation (SCS) reduces neuropathic pain. It focuses on the role of colony-stimulating factor 1 (CSF1) and microglial activation in the spinal cord. The researchers used a rat model of chronic constriction injury (CCI) to mimic neuropathic pain. They found that SCS can alleviate pain by reducing microglial activation, which is linked to decreased CSF1 levels. The key finding is that SCS inhibits the release of CSF1 from the dorsal root ganglion to the spinal cord. This inhibition then reduces microglial activation and, consequently, neuropathic pain.

Study Duration

21 days

Participants

Sprague-Dawley rats (males weighing 280–320 g)

Evidence Level

Original Laboratory Research Report

Key Findings

1
SCS significantly increased the mechanical withdrawal threshold in CCI rats, indicating pain relief.
2
SCS attenuated microglial activation in the spinal dorsal horn of CCI rats, suggesting reduced inflammation.
3
SCS reduced CSF1 levels in the spinal dorsal horn and dorsal roots, but not in the dorsal root ganglion, implying inhibited transmission of CSF1.

Research Summary

This study demonstrates that spinal cord stimulation (SCS) can alleviate neuropathic pain in rats by inhibiting the transmission of colony-stimulating factor 1 (CSF1) from the dorsal root ganglion (DRG) to the spinal cord. The reduction in CSF1 leads to decreased microglial activation and reduced production of proinflammatory cytokines in the spinal cord, which are key factors in SCS-induced pain relief. Intrathecal injection of recombinant CSF1 protein abolished the beneficial effects of SCS on analgesia and microglial activation, confirming the role of CSF1 downregulation in SCS-mediated pain relief.

Practical Implications

New Therapeutic Target

CSF1 signaling pathway represents a potential therapeutic target for treating neuropathic pain.

Mechanism Elucidation

The study provides new insight into the mechanisms by which SCS alleviates chronic neuropathic pain.

Optimizing SCS Parameters

Duration of stimulation is an important factor influencing the effect of SCS on microglial activation in the spinal dorsal horn.

Study Limitations

1
The study did not demonstrate how SCS affects CSF1 release from nerve-injured DRG neurons.
2
Thermal withdrawal thresholds were not assessed.
3
Lack of mood assessment tools to assess anxiety and depression

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