ArticleScientific reports2026
Biphasic modulation of large-fiber excitability accompanied by dynamic nerve-intrinsic immune activation following CFA-induced peripheral inflammation in mice.
Article in Scientific reports, 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Not yet cited in PubMed.
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Abstract
Peripheral inflammation is known to enhance pain sensitivity through nociceptive pathways, but its impact on large-diameter myelinated fibers, which mediate touch and proprioception, is less understood. Here, we examined the temporal dynamics of large fiber (Aα/β) excitability in a mouse model of Complete Freund's Adjuvant (CFA)-induced hind paw inflammation, integrating behavioral, electrophysiological, proteomic, and immune analyses. CFA induced a biphasic modulation of large fiber function, with early hypoexcitability on day 1 followed by hyperexcitability on day 7, temporally aligned with thermal hypersensitivity. Proteomic analysis of sciatic nerve tissue on day 7 revealed upregulation of immune-related proteins, including CD45, providing proteomic evidence of local nerve inflammation. Systemic cytokines and paw skin thrombin activity showed transient elevations at early time points. In vitro, lipopolysaccharide-stimulated Schwannoma-derived cells modulated thrombin activity and altered expression of complement- and inflammation-associated genes. These findings demonstrate that peripheral inflammation dynamically modulates large fiber excitability alongside intrinsic neural and systemic immune responses, highlighting the importance of considering multi-level neuro-immune interactions in models of peripheral nerve function.
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