Notch signaling pathway: a new target for neuropathic pain therapy.

Yan Zhang, Tingting Wang, Sanlan Wu, Li Tang, Jia Wang, Jinghan Yang, Shanglong Yao, Yan Zhang

Journal: The journal of headache and pain 2023;24(1):87

PMID: 37454050

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Abstract

The Notch gene, a highly evolutionarily conserved gene, was discovered approximately 110 years ago and has been found to play a crucial role in the development of multicellular organisms. Notch receptors and their ligands are single-pass transmembrane proteins that typically require cellular interactions and proteolytic processing to facilitate signal transduction. Recently, mounting evidence has shown that aberrant activation of the Notch is correlated with neuropathic pain. The activation of the Notch signaling pathway can cause the activation of neuroglia and the release of pro-inflammatory factors, a key mechanism in the development of neuropathic pain. Moreover, the Notch signaling pathway may contribute to the persistence of neuropathic pain by enhancing synaptic transmission and calcium inward flow. This paper reviews the structure and activation of the Notch signaling pathway, as well as its potential mechanisms of action, to provide novel insights for future treatments of neuropathic pain.

Address: Department of Anesthesiology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, 1277 Jiefang Avenue, Wuhan, 430022, China.; Institute of Anesthesia and Critical Care Medicine, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430022, China.; Key Laboratory of Anesthesiology and Resuscitation (Huazhong University of Science and Technology), Ministry of Education, Wuhan, China.; Department of Pharmacy, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430022, China.; Department of Pain, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, 1277 Jiefang Avenue, Wuhan, 430022, China.; The Key Laboratory of Biomedical Information Engineering of Ministry of Education, Institute of Health and Rehabilitation Science, Research Center for Brain-Inspired Intelligence, School of Life Science and Technology, Xi'an Jiaotong University, The Key Laboratory of Neuro-Informatics & Rehabilitation En-Gineering of Ministry of Civil Affairs, Xi'an, Shaanxi, P. R. China.; Department of Cardiovascular Surgery, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, 1277 Jiefang Ave, Wuhan, 430022, Hubei, China.; Department of Anesthesiology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, 1277 Jiefang Avenue, Wuhan, 430022, China. [email protected].; Institute of Anesthesia and Critical Care Medicine, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430022, China. [email protected].; Key Laboratory of Anesthesiology and Resuscitation (Huazhong University of Science and Technology), Ministry of Education, Wuhan, China. [email protected].; Department of Anesthesiology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, 1277 Jiefang Avenue, Wuhan, 430022, China. [email protected].; Institute of Anesthesia and Critical Care Medicine, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430022, China. [email protected].; Key Laboratory of Anesthesiology and Resuscitation (Huazhong University of Science and Technology), Ministry of Education, Wuhan, China. [email protected].; Department of Pain, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, 1277 Jiefang Avenue, Wuhan, 430022, China. [email protected].

DOI: 10.1186/s10194-023-01616-y

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MeSH Terms: Humans, Signal Transduction, Membrane Proteins, Neuralgia, Receptors, Notch