The complement cascade in the regulation of neuroinflammation, nociceptive sensitization, and pain

Charles A Warwick; Alex L Keyes; Trent M Woodruff; Yuriy M Usachev

doi:10.1016/j.jbc.2021.101085

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The complement cascade in the regulation of neuroinflammation, nociceptive sensitization, and pain

Journal article

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The complement cascade in the regulation of neuroinflammation, nociceptive sensitization, and pain

Charles A Warwick, Alex L Keyes, Trent M Woodruff and Yuriy M Usachev

The Journal of biological chemistry, Vol.297(3), 101085

08/16/2021

DOI: 10.1016/j.jbc.2021.101085

PMCID: PMC8446806

PMID: 34411562

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Abstract

The complement cascade is a key component of the innate immune system that is rapidly recruited through a cascade of enzymatic reactions to enable the recognition and clearance of pathogens and promote tissue repair. Despite its well understood role in immunology, recent studies have highlighted new and unexpected roles of the complement cascade in neuro-immune interaction and in the regulation of neuronal processes during development, aging, and in disease states. Complement signaling is particularly important in directing neuronal responses to tissue injury, neurotrauma, and nerve lesions. Under physiological conditions, complement-dependent changes in neuronal excitability, synaptic strength, and neurite remodeling promote nerve regeneration, tissue repair, and healing. However, in a variety of pathologies, dysregulation of the complement cascade leads to chronic inflammation, persistent pain, and neural dysfunction. This review describes recent advances in our understanding of the multifaceted cross-communication that takes place between the complement system and neurons. In particular, we focus on the molecular and cellular mechanisms through which complement signaling regulates neuronal excitability and synaptic plasticity in the nociceptive pathways involved in pain processing in both health and disease. Finally, we discuss the future of this rapidly growing field and what we believe to be the significant knowledge gaps that need to be addressed.

Neuroimmunology

Pain

axon

complement

complement system

neurodegeneration

neuroinflammation

neurological disease

neuron

synapse

Details

Title: Subtitle: The complement cascade in the regulation of neuroinflammation, nociceptive sensitization, and pain
Creators: Charles A Warwick - Department of Neurobiology, Pittsburgh Center for Pain Research, University of Pittsburgh, Pittsburgh, PA 15213
Alex L Keyes - Department of Neuroscience and Pharmacology, Iowa Neuroscience Institute, University of Iowa, Iowa City, IA 52242
Trent M Woodruff - School of Biomedical Sciences, University of Queensland, St.Lucia, QLD 4072, Australia
Yuriy M Usachev - Department of Neuroscience and Pharmacology, Iowa Neuroscience Institute, University of Iowa, Iowa City, IA 52242
Resource Type: Journal article
Publication Details: The Journal of biological chemistry, Vol.297(3), 101085
DOI: 10.1016/j.jbc.2021.101085
PMID: 34411562
PMCID: PMC8446806
NLM abbreviation: J Biol Chem
ISSN: 0021-9258
eISSN: 1083-351X
Publisher: Elsevier Inc
Grant note: DOI: 10.13039/501100000265, name: MRC, award: 1082271; DOI: 10.13039/501100000925, name: National Health and Medical Research Council; DOI: 10.13039/100000002, name: National Institutes of Health, award: DK116624, NS096246, NS113189
Language: English
Date published: 08/16/2021
Academic Unit: Iowa Neuroscience Institute; Anesthesia; Neuroscience and Pharmacology
Record Identifier: 9984122680202771

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