PXD066745-1

PXD066745 is an original dataset announced via ProteomeXchange.

Title	Phosphoproteomics Uncovers a Neuroimmune Perspective on Trigeminal Neuralgia: Sexually Dimorphic Regulatory Networks Linking Calcium Channels to the Complement Cascade
Description	Background: Trigeminal neuralgia (TN) is a debilitating neuropathic pain disorder with a higher prevalence in females, yet its pathogenic mechanisms and underlying sexual dimorphism remain incompletely understood. Phosphorylation modifications are critical regulators of pain signaling, but comprehensive phosphoproteomic profiling of TN has not been reported. Methods: We established a chronic constriction injury model of the infraorbital nerve (ION-CCI) in male and female rats via an intraoral approach. Mechanical allodynia was behaviorally confirmed. Integrated proteomic and phosphoproteomic analyses of trigeminal ganglia were performed at postoperative day 7 using data-independent acquisition mass spectrometry. Bioinformatic analyses included pathway enrichment, kinase-substrate prediction, and drug target annotation. Results: Key findings include: (1) Proteomics identified 5,820 proteins and phosphoproteomics revealed 8,830 phosphopeptides mapping to 8,139 phosphoproteins; (2) Complement component C1qa was upregulated in both sexes, while kininogen (KNG1/2) showed female-specific elevation; (3) MAPK pathway activation was prominent, with significantly increased HSPB1 phosphorylation at S86, predicted to be regulated by MAPKAPK2/3; (4) N-type calcium channel (CACN1B) phosphorylation was enhanced in both sexes, suggesting a CACN1B-MAPK-HSPB1 signaling axis; (5) Drug annotation identified Ziconotide (CACN1B blocker) as a therapeutic candidate. Conclusions: This study reveals a neuroimmune phosphorylation network in TN pathogenesis, establishing complement activation and the CACN1B-MAPK-HSPB1 axis as central mechanisms. Sexually dimorphic expression of complement and kinin components provides molecular insights into TN's female predominance. These findings offer therapeutic targets and support sex-specific immunomodulatory strategies for TN.
HostingRepository	PRIDE
AnnounceDate	2026-02-26
AnnouncementXML	Submission_2026-02-25_19:14:59.915.xml
DigitalObjectIdentifier
ReviewLevel	Peer-reviewed dataset
DatasetOrigin	Original dataset
RepositorySupport	Unsupported dataset by repository
PrimarySubmitter	xiaojie zhai
SpeciesList	scientific name: Rattus norvegicus (Rat); NCBI TaxID: NEWT:10116;
ModificationList	phosphorylated residue
Instrument	timsTOF Pro

Revision	Datetime	Status	ChangeLog Entry
0	2025-07-29 23:14:02	ID requested
⏵ 1	2026-02-25 19:15:00	announced

10.3389/FIMMU.2026.1676019;

submitter keyword: rigeminal neuralgia

phosphoproteomics

neuroimmune crosstalk

complement C1q

MAPKAPK2–HSPB1 axis

Xiaojie Zhai
contact affiliation	Anesthesiology Department, The First Affiliated Hospital of Ningbo University, Ningbo, China
contact email	fyyzhaixiaojie@nbu.edu.cn
lab head
xiaojie zhai
contact affiliation	宁波大学附属第一医院
contact email	fyyzhaixiaojie@nbu.edu.cn
dataset submitter

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PRIDE project URI

• PRIDE
  1. PXD066745
     1. Label: PRIDE project
     2. Name: Phosphoproteomics Uncovers a Neuroimmune Perspective on Trigeminal Neuralgia: Sexually Dimorphic Regulatory Networks Linking Calcium Channels to the Complement Cascade