Serpinb2 is Upregulated in Dorsal Root Ganglia and Associated With Neuroinflammatory Changes in a Mouse Model of Neuropathic Pain.

BACKGROUND

Neuropathic pain (NP) is a refractory chronic pain condition that severely impairs quality of life, while currently available treatments often provide insufficient relief. Emerging evidence indicates that neuroinflammation in the dorsal root ganglion (DRG) is critically involved in the development and maintenance of NP; however, the molecular mechanisms responsible for this process remain to be elucidated. The aim of this study was to identify and validate key genes involved in NP and to investigate their potential as therapeutic targets.

METHODS

Integrated bioinformatic analyses were performed using multiple DRG transcriptomic datasets derived from a spared nerve injury (SNI) model. Differential expression analysis and weighted gene co-expression network analysis were used to identify NP-associated genes, followed by functional enrichment analyses. Experimental validation was subsequently conducted in an SNI mouse model. Mechanical sensitivity and anxiety-like behaviors were assessed, and the expression of candidate genes in ipsilateral L4-L6 DRGs was examined using quantitative reverse transcription quantitative polymerase chain reaction (RT-qPCR) and immunohistochemistry.

RESULTS

Eight candidate genes associated with NP were identified through integrated bioinformatic analyses. Among these, serpin family B member 2; plasminogen activator inhibitor-2, PAI-2 (Serpinb2) was consistently upregulated across datasets. The well-established pain-related gene sodium voltage-gated channel alpha subunit 3 (Scn3a) was included as a reference. Serpinb2-associated gene networks were primarily enriched in inflammatory and immune-related pathways. SNI mice developed significant mechanical allodynia and anxiety-like behaviors. Consistent with these findings, Serpinb2 expression was significantly increased in DRG tissues at both the mRNA and protein levels.

CONCLUSIONS

Serpinb2 may represent a previously underappreciated molecule associated with DRG neuroinflammation in NP and may serve as a potential target for further investigation.