Characterization of preclinical models to investigate spinal cord stimulation for neuropathic pain: a systematic review and meta-analysis

Abstract. Despite advancements in preclinical and clinical spinal cord stimulation (SCS) research, the mechanisms of SCS action remain unclear. This may result from challenges in translatability of findings between species. Our systematic review (PROSPERO: CRD42023457443) aimed to comprehensively ch...

Full description

Saved in:
Bibliographic Details
Main Authors: Dave Mugan, Quoc C. Vuong, Birte E. Dietz, Ilona Obara
Format: Article
Language:English
Published: Wolters Kluwer 2025-02-01
Series:PAIN Reports
Online Access:http://journals.lww.com/painrpts/fulltext/10.1097/PR9.0000000000001228
Tags: Add Tag
No Tags, Be the first to tag this record!
_version_ 1832589606177996800
author Dave Mugan
Quoc C. Vuong
Birte E. Dietz
Ilona Obara
author_facet Dave Mugan
Quoc C. Vuong
Birte E. Dietz
Ilona Obara
author_sort Dave Mugan
collection DOAJ
description Abstract. Despite advancements in preclinical and clinical spinal cord stimulation (SCS) research, the mechanisms of SCS action remain unclear. This may result from challenges in translatability of findings between species. Our systematic review (PROSPERO: CRD42023457443) aimed to comprehensively characterize the important translational components of preclinical SCS models, including stimulating elements and stimulation specifications. Databases (Embase, PubMed, Web of Science, and WikiStim) were searched on October 5, 2023, identifying 78 studies meeting the search criteria. We conducted a post hoc meta-analysis, including subgroup analyses and meta-regression, to assess SCS efficacy on mechanical hypersensitivity in rats subjected to neuropathic pain. Although monopolar electrodes were predominantly used as stimulating elements until 2013, quadripolar paddle and cylindrical leads gained recent popularity. Most research was conducted using 50 Hz and 200 µs stimulation. Motor threshold (MT) estimation was the predominant strategy to determine SCS intensity, which was set to 71.9% of MT on average. Our analysis revealed a large effect size for SCS (Hedge g = 1.13, 95% CI: [0.93, 1.32]) with similar magnitudes of effect between conventional (≤100 Hz) and nonconventional SCS paradigms while sham SCS had nonsignificant effect size. In addition, different stimulation intensity, frequency, and electrode design did not affect effect size. The risk of bias was assessed using Systematic Review Centre for Laboratory animal Experimentation criteria and was unclear, and only the frequency subgroup analysis showed publication bias. In summary, our review characterizes the critical components of preclinical SCS models and provides recommendations to improve reproducibility and translatability, thereby advancing the scientific foundation for SCS research.
format Article
id doaj-art-027428caff68428da3678a80e496501d
institution Kabale University
issn 2471-2531
language English
publishDate 2025-02-01
publisher Wolters Kluwer
record_format Article
series PAIN Reports
spelling doaj-art-027428caff68428da3678a80e496501d2025-01-24T09:20:44ZengWolters KluwerPAIN Reports2471-25312025-02-01101e122810.1097/PR9.0000000000001228PR90000000000001228Characterization of preclinical models to investigate spinal cord stimulation for neuropathic pain: a systematic review and meta-analysisDave Mugan0Quoc C. Vuong1Birte E. Dietz2Ilona Obara3a School of Pharmacy, Newcastle University, Newcastle-upon-Tyne, United Kingdomd Biosciences Institute, Newcastle University, Newcastle-upon-Tyne, United Kingdoma School of Pharmacy, Newcastle University, Newcastle-upon-Tyne, United Kingdoma School of Pharmacy, Newcastle University, Newcastle-upon-Tyne, United KingdomAbstract. Despite advancements in preclinical and clinical spinal cord stimulation (SCS) research, the mechanisms of SCS action remain unclear. This may result from challenges in translatability of findings between species. Our systematic review (PROSPERO: CRD42023457443) aimed to comprehensively characterize the important translational components of preclinical SCS models, including stimulating elements and stimulation specifications. Databases (Embase, PubMed, Web of Science, and WikiStim) were searched on October 5, 2023, identifying 78 studies meeting the search criteria. We conducted a post hoc meta-analysis, including subgroup analyses and meta-regression, to assess SCS efficacy on mechanical hypersensitivity in rats subjected to neuropathic pain. Although monopolar electrodes were predominantly used as stimulating elements until 2013, quadripolar paddle and cylindrical leads gained recent popularity. Most research was conducted using 50 Hz and 200 µs stimulation. Motor threshold (MT) estimation was the predominant strategy to determine SCS intensity, which was set to 71.9% of MT on average. Our analysis revealed a large effect size for SCS (Hedge g = 1.13, 95% CI: [0.93, 1.32]) with similar magnitudes of effect between conventional (≤100 Hz) and nonconventional SCS paradigms while sham SCS had nonsignificant effect size. In addition, different stimulation intensity, frequency, and electrode design did not affect effect size. The risk of bias was assessed using Systematic Review Centre for Laboratory animal Experimentation criteria and was unclear, and only the frequency subgroup analysis showed publication bias. In summary, our review characterizes the critical components of preclinical SCS models and provides recommendations to improve reproducibility and translatability, thereby advancing the scientific foundation for SCS research.http://journals.lww.com/painrpts/fulltext/10.1097/PR9.0000000000001228
spellingShingle Dave Mugan
Quoc C. Vuong
Birte E. Dietz
Ilona Obara
Characterization of preclinical models to investigate spinal cord stimulation for neuropathic pain: a systematic review and meta-analysis
PAIN Reports
title Characterization of preclinical models to investigate spinal cord stimulation for neuropathic pain: a systematic review and meta-analysis
title_full Characterization of preclinical models to investigate spinal cord stimulation for neuropathic pain: a systematic review and meta-analysis
title_fullStr Characterization of preclinical models to investigate spinal cord stimulation for neuropathic pain: a systematic review and meta-analysis
title_full_unstemmed Characterization of preclinical models to investigate spinal cord stimulation for neuropathic pain: a systematic review and meta-analysis
title_short Characterization of preclinical models to investigate spinal cord stimulation for neuropathic pain: a systematic review and meta-analysis
title_sort characterization of preclinical models to investigate spinal cord stimulation for neuropathic pain a systematic review and meta analysis
url http://journals.lww.com/painrpts/fulltext/10.1097/PR9.0000000000001228
work_keys_str_mv AT davemugan characterizationofpreclinicalmodelstoinvestigatespinalcordstimulationforneuropathicpainasystematicreviewandmetaanalysis
AT quoccvuong characterizationofpreclinicalmodelstoinvestigatespinalcordstimulationforneuropathicpainasystematicreviewandmetaanalysis
AT birteedietz characterizationofpreclinicalmodelstoinvestigatespinalcordstimulationforneuropathicpainasystematicreviewandmetaanalysis
AT ilonaobara characterizationofpreclinicalmodelstoinvestigatespinalcordstimulationforneuropathicpainasystematicreviewandmetaanalysis