Prokineticin-2 Participates in Chronic Constriction Injury-Triggered Neuropathic Pain and Anxiety via Regulated by NF-κB in Nucleus Accumbens Shell in Rats

© 2023. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature..

Neuropathic pain (NP) is an intractable pain that results from primary nervous system injury and dysfunction. Herein, we demonstrated in animal models that peripheral nerve injury induced enhanced pain perception and anxiety-like behaviors. According to previous reports, nucleus accumbens (NAc) shell is required for complete expression of neuropathic pain behaviors and mood alternations, we found the elevated mRNA and protein level of Prokineticin-2 (Prok2) in the NAc shell after Chronic Constriction Injury (CCI). Prok2 knockdown in the NAc shell reversed NP and anxiety-like behaviors in rats, indicating that Prok2 might play a fundamental role in NP and anxiety co-morbidity. CCI significantly enhanced Prok2 co-expression with NF-κB P-p65 in comparison with control animals. In addition to reversing the established nociceptive hypersensitivities and anxiety simultaneously, NAc microinjection of NF-κB siRNA or specific inhibitor PDTC reversed Prok2 upregulation. Besides, Prok2 was significantly decreased in vitro when co-transfected with si-NF-κB. Dual-Luciferase assay showed NF-κB directly activated Prok2 gene transcriptional activity. Overall, these findings provide new insights into the neurobiological mechanisms behind NP and comorbid anxiety. The NF-κB/Prok2 pathway could be a potential therapeutic target for NP and anxiety disorders.

Medienart:

E-Artikel

Erscheinungsjahr:

2024

Erschienen:

2024

Enthalten in:

Zur Gesamtaufnahme - volume:61

Enthalten in:

Molecular neurobiology - 61(2024), 5 vom: 01. Mai, Seite 2764-2783

Sprache:

Englisch

Beteiligte Personen:

Wang, Wenting [VerfasserIn]
Yuan, Meng [VerfasserIn]
Xu, Yaowei [VerfasserIn]
Yang, Jingjie [VerfasserIn]
Wang, Xiaoling [VerfasserIn]
Zhou, Yifan [VerfasserIn]
Yu, Zhixiang [VerfasserIn]
Lu, Zhongyuan [VerfasserIn]
Wang, Yiming [VerfasserIn]
Hu, Chenge [VerfasserIn]
Bai, Qian [VerfasserIn]
Li, Zhisong [VerfasserIn]

Links:

Volltext

Themen:

Anxiety
Gastrointestinal Hormones
Journal Article
NF-kappa B
Neuropathic pain
Neuropeptides
Nuclear factor κB P-p65
Nucleus accumbens shell
Prok2 protein, rat
Prokineticin 2

Anmerkungen:

Date Completed 24.04.2024

Date Revised 02.05.2024

published: Print-Electronic

Citation Status MEDLINE

doi:

10.1007/s12035-023-03680-6

funding:

Förderinstitution / Projekttitel:

PPN (Katalog-ID):

NLM364261986