Single-cell analyses identify persistent neuroimmune remodeling and prioritize SPP1 and LGALS3 in neuropathic pain
Abstract
IntroductionPersistent neuropathic pain involves lasting sensory and immune changes. We examined which expression programs persist across injury settings and whether prioritized genes are associated with pain severity.MethodsWe analyzed five public single-cell or single-nucleus transcriptomic resources and two independent bulk RNA-sequencing resources, then examined tissue expression and behavior in spared nerve injury experiments.ResultsMicroglial expression showed a distinct early response and persistent glial-program activity. The glial signature remained elevated at day 14 and month 5 after exclusion of Spp1 and Lgals3 (false-discovery-adjusted q=0.0473 and 0.00128). Independent bulk data supported neuronal injury-related and glial programs, although candidate-gene effects varied across populations and stages. Spp1 and Lgals3 retained high priority in ranking sensitivity analyses, and their dorsal root ganglion expression correlated with mechanical hypersensitivity after adjustment for collection endpoint. Post-injury Lumogallion treatment increased the day-14 paw-withdrawal threshold (treated/vehicle geometric-mean ratio 4.08, 95% confidence interval 2.53–6.55) and reduced selected dorsal root ganglion and spinal transcripts. Structural modeling proposed an LGALS3–Lumogallion interaction for experimental testing.DiscussionThese findings link persistent neuroimmune expression programs to tissue-level Spp1 and Lgals3 associations and show partial behavioral improvement with Lumogallion. Direct target-engagement studies are planned to determine whether LGALS3 contributes to this response.
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BibTeX
@article{li2026singlecell,
title = {{Single-cell analyses identify persistent neuroimmune remodeling and prioritize SPP1 and LGALS3 in neuropathic pain}},
author = {Jianhui Li and Shanghai Ma and Kaisheng Ye and Bin Zhang},
journal = {Frontiers in Immunology},
year = {2026},
month = nov,
doi = {10.3389/fimmu.2026.1981038},
url = {https://www.frontiersin.org/articles/10.3389/fimmu.2026.1981038},
note = {CC BY 4.0},
}
RIS
TY - JOUR
TI - Single-cell analyses identify persistent neuroimmune remodeling and prioritize SPP1 and LGALS3 in neuropathic pain
AU - Jianhui Li
AU - Shanghai Ma
AU - Kaisheng Ye
AU - Bin Zhang
PY - 2026
DA - 2026/11/04
JO - Frontiers in Immunology
DO - 10.3389/fimmu.2026.1981038
UR - https://www.frontiersin.org/articles/10.3389/fimmu.2026.1981038
AB - IntroductionPersistent neuropathic pain involves lasting sensory and immune changes. We examined which expression programs persist across injury settings and whether prioritized genes are associated with pain severity.MethodsWe analyzed five public single-cell or single-nucleus transcriptomic resources and two independent bulk RNA-sequencing resources, then examined tissue expression and behavior in spared nerve injury experiments.ResultsMicroglial expression showed a distinct early response and persistent glial-program activity. The glial signature remained elevated at day 14 and month 5 after exclusion of Spp1 and Lgals3 (false-discovery-adjusted q=0.0473 and 0.00128). Independent bulk data supported neuronal injury-related and glial programs, although candidate-gene effects varied across populations and stages. Spp1 and Lgals3 retained high priority in ranking sensitivity analyses, and their dorsal root ganglion expression correlated with mechanical hypersensitivity after adjustment for collection endpoint. Post-injury Lumogallion treatment increased the day-14 paw-withdrawal threshold (treated/vehicle geometric-mean ratio 4.08, 95% confidence interval 2.53–6.55) and reduced selected dorsal root ganglion and spinal transcripts. Structural modeling proposed an LGALS3–Lumogallion interaction for experimental testing.DiscussionThese findings link persistent neuroimmune expression programs to tissue-level Spp1 and Lgals3 associations and show partial behavioral improvement with Lumogallion. Direct target-engagement studies are planned to determine whether LGALS3 contributes to this response.
SN - 1664-3224
ER -