Low intensity trans‑spinal focused ultrasound reduces mechanical sensitivity and suppresses spinal microglia activation in rats with chronic constriction injury

Bioelectronic Medicine, 2025 · DOI: https://doi.org/10.1186/s42234-025-00170-z · Published: March 6, 2025

Simple Explanation

This study explores the potential of trans-spinal focused ultrasound (tsFUS) to alleviate neuropathic pain in rats with chronic constriction injury (CCI). The rats received either tsFUS or a sham treatment targeting the L5 spinal segment for 3 minutes daily over three days. The effect of the treatment was evaluated by measuring mechanical sensitivity and assessing spinal microglia activation. The researchers found that tsFUS treatment was associated with increased von Frey Threshold (vFT), a measure of mechanical sensitivity, compared to the sham treatment. This increase persisted beyond the treatment period. Furthermore, tsFUS treatment reduced the counts of spinal microglia and activated, pro-inflammatory microglia in the insonified side of the spinal cord. These findings suggest that tsFUS may be a promising approach for treating neuropathic pain at early stages. This is possibly achieved by attenuating the development of microglial-driven inflammation.

Study Duration

23 days post-CCI

Participants

40 male Sprague–Dawley rats

Evidence Level

Not specified

Key Findings

1
tsFUS treatment increased the von Frey threshold (vFT) in rats with CCI compared to sham treatment, indicating reduced mechanical sensitivity. This effect persisted for up to 23 days post-CCI.
2
tsFUS treatment reduced the number of spinal microglia (Iba1+ cells) in the ipsilateral side of the spinal cord in CCI rats, as determined by immunohistochemistry.
3
tsFUS treatment suppressed the activation of microglia, specifically reducing the number of activated, pro-inflammatory microglia (Iba1+/CD86+ cells), in the ipsilateral side of the spinal cord in CCI rats, as shown by flow cytometry.

Research Summary

The study investigated the effects of low-intensity trans-spinal focused ultrasound (tsFUS) on neuropathic pain in rats with chronic constriction injury (CCI). tsFUS was applied to the L5 spinal segment, and its effects on mechanical sensitivity and spinal microglia activation were assessed. Results showed that tsFUS treatment increased the von Frey threshold, indicating reduced mechanical sensitivity, and suppressed the activation of spinal microglia in the ipsilateral side of the spinal cord. These effects were sustained for several weeks after treatment. The findings suggest that tsFUS may be a promising non-invasive neuromodulation approach for the treatment of neuropathic pain, potentially by attenuating microglial-driven inflammation.

Practical Implications

Potential Neuropathic Pain Treatment

tsFUS could offer a non-invasive alternative or adjunct therapy for managing neuropathic pain, especially in early stages.

Targeted Anti-Inflammatory Approach

tsFUS can be used to modulate microglial activity and reduce neuroinflammation in a localized manner within the spinal cord.

Further Research on Spinal Cord Disorders

The study supports further investigation of tsFUS for modulating circuits involved in pain-related disorders or spinal cord injury.

Study Limitations

1
The study examined tsFUS only in the early phase of neuropathic pain.
2
tsFUS was tested only in adult male rats.
3
Only one set of tsFUS parameters (PRF, duty cycle, mechanical index, duration and localization) was tested.

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