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

Abstract Low intensity, trans-spinal focused ultrasound (tsFUS) is a noninvasive neuromodulation approach that has been shown to modulate spinal circuit excitability in healthy rats. Here, we evaluated the potential of tsFUS for alleviating neuropathic pain by testing it in a chronic constriction in...

Full description

Saved in:
Bibliographic Details
Main Authors: Weiguo Song, Alice Giannotti, Alexandra Bekiaridou, Ona Bloom, Stavros Zanos
Format: Article
Language:English
Published: BMC 2025-03-01
Series:Bioelectronic Medicine
Subjects:
Online Access:https://doi.org/10.1186/s42234-025-00170-z
Tags: Add Tag
No Tags, Be the first to tag this record!
_version_ 1850265627142389760
author Weiguo Song
Alice Giannotti
Alexandra Bekiaridou
Ona Bloom
Stavros Zanos
author_facet Weiguo Song
Alice Giannotti
Alexandra Bekiaridou
Ona Bloom
Stavros Zanos
author_sort Weiguo Song
collection DOAJ
description Abstract Low intensity, trans-spinal focused ultrasound (tsFUS) is a noninvasive neuromodulation approach that has been shown to modulate spinal circuit excitability in healthy rats. Here, we evaluated the potential of tsFUS for alleviating neuropathic pain by testing it in a chronic constriction injury (CCI) model. Male rats underwent CCI of the left sciatic nerve and then received tsFUS (2 kHz pulse repetition frequency; 40% duty cycle) or sham stimulation, targeted at spinal segment level L5 for 3 min daily over three days. As expected, CCI causes significant reduction of von Frey Threshold (vFT), a measure of mechanical sensitivity. We found that tsFUS treatment is associated with increased vFT compared to sham; this increase persists beyond the duration of treatment, through days 4 to 23 post-CCI. In spinal cords of tsFUS-treated animals, counts of spinal microglia (Iba1 + cells) and of activated, pro-inflammatory microglia (Iba1 + /CD86 + cells), are reduced compared to sham-treated animals. This reduction in microglia counts is limited to the insonified side of the spinal cord, ipsilateral to CCI. These findings suggest that tsFUS may be a promising approach for treatment of neuropathic pain at early stages, possibly by attenuating the development of microglial-driven inflammation.
format Article
id doaj-art-5bf68470c19343ef921a790fcad94b98
institution OA Journals
issn 2332-8886
language English
publishDate 2025-03-01
publisher BMC
record_format Article
series Bioelectronic Medicine
spelling doaj-art-5bf68470c19343ef921a790fcad94b982025-08-20T01:54:22ZengBMCBioelectronic Medicine2332-88862025-03-0111111010.1186/s42234-025-00170-zLow intensity trans-spinal focused ultrasound reduces mechanical sensitivity and suppresses spinal microglia activation in rats with chronic constriction injuryWeiguo Song0Alice Giannotti1Alexandra Bekiaridou2Ona Bloom3Stavros Zanos4Feinstein Institutes for Medical ResearchThe Biorobotics Institute and Department of Excellence in Robotics and AI, Scuola Superiore Sant’AnnaElmezzi Graduate School of Molecular MedicineFeinstein Institutes for Medical ResearchFeinstein Institutes for Medical ResearchAbstract Low intensity, trans-spinal focused ultrasound (tsFUS) is a noninvasive neuromodulation approach that has been shown to modulate spinal circuit excitability in healthy rats. Here, we evaluated the potential of tsFUS for alleviating neuropathic pain by testing it in a chronic constriction injury (CCI) model. Male rats underwent CCI of the left sciatic nerve and then received tsFUS (2 kHz pulse repetition frequency; 40% duty cycle) or sham stimulation, targeted at spinal segment level L5 for 3 min daily over three days. As expected, CCI causes significant reduction of von Frey Threshold (vFT), a measure of mechanical sensitivity. We found that tsFUS treatment is associated with increased vFT compared to sham; this increase persists beyond the duration of treatment, through days 4 to 23 post-CCI. In spinal cords of tsFUS-treated animals, counts of spinal microglia (Iba1 + cells) and of activated, pro-inflammatory microglia (Iba1 + /CD86 + cells), are reduced compared to sham-treated animals. This reduction in microglia counts is limited to the insonified side of the spinal cord, ipsilateral to CCI. These findings suggest that tsFUS may be a promising approach for treatment of neuropathic pain at early stages, possibly by attenuating the development of microglial-driven inflammation.https://doi.org/10.1186/s42234-025-00170-zTrans-spinal focused ultrasound stimulationNoninvasive neuromodulationVon Frey thresholdPainFlow cytometryMicroglia
spellingShingle Weiguo Song
Alice Giannotti
Alexandra Bekiaridou
Ona Bloom
Stavros Zanos
Low intensity trans-spinal focused ultrasound reduces mechanical sensitivity and suppresses spinal microglia activation in rats with chronic constriction injury
Bioelectronic Medicine
Trans-spinal focused ultrasound stimulation
Noninvasive neuromodulation
Von Frey threshold
Pain
Flow cytometry
Microglia
title Low intensity trans-spinal focused ultrasound reduces mechanical sensitivity and suppresses spinal microglia activation in rats with chronic constriction injury
title_full Low intensity trans-spinal focused ultrasound reduces mechanical sensitivity and suppresses spinal microglia activation in rats with chronic constriction injury
title_fullStr Low intensity trans-spinal focused ultrasound reduces mechanical sensitivity and suppresses spinal microglia activation in rats with chronic constriction injury
title_full_unstemmed Low intensity trans-spinal focused ultrasound reduces mechanical sensitivity and suppresses spinal microglia activation in rats with chronic constriction injury
title_short Low intensity trans-spinal focused ultrasound reduces mechanical sensitivity and suppresses spinal microglia activation in rats with chronic constriction injury
title_sort low intensity trans spinal focused ultrasound reduces mechanical sensitivity and suppresses spinal microglia activation in rats with chronic constriction injury
topic Trans-spinal focused ultrasound stimulation
Noninvasive neuromodulation
Von Frey threshold
Pain
Flow cytometry
Microglia
url https://doi.org/10.1186/s42234-025-00170-z
work_keys_str_mv AT weiguosong lowintensitytransspinalfocusedultrasoundreducesmechanicalsensitivityandsuppressesspinalmicrogliaactivationinratswithchronicconstrictioninjury
AT alicegiannotti lowintensitytransspinalfocusedultrasoundreducesmechanicalsensitivityandsuppressesspinalmicrogliaactivationinratswithchronicconstrictioninjury
AT alexandrabekiaridou lowintensitytransspinalfocusedultrasoundreducesmechanicalsensitivityandsuppressesspinalmicrogliaactivationinratswithchronicconstrictioninjury
AT onabloom lowintensitytransspinalfocusedultrasoundreducesmechanicalsensitivityandsuppressesspinalmicrogliaactivationinratswithchronicconstrictioninjury
AT stavroszanos lowintensitytransspinalfocusedultrasoundreducesmechanicalsensitivityandsuppressesspinalmicrogliaactivationinratswithchronicconstrictioninjury