Nociceptive sensitization by complement C5a and C3a in mouse

Jun Ho Jang; J. David Clark; Xiangqi Li; Matthew S Yorek; Yuriy M Usachev; Timothy J Brennan

doi:10.1016/j.pain.2009.11.021

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Nociceptive sensitization by complement C5a and C3a in mouse

Journal article

Peer reviewed

Nociceptive sensitization by complement C5a and C3a in mouse

Jun Ho Jang, J. David Clark, Xiangqi Li, Matthew S Yorek, Yuriy M Usachev and Timothy J Brennan

Pain (Amsterdam), Vol.148(2), pp.343-352

2010

DOI: 10.1016/j.pain.2009.11.021

PMCID: PMC2814960

PMID: 20031321

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https://www.ncbi.nlm.nih.gov/pmc/articles/2814960View

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Abstract

Activation of the complement system by injury increases inflammation by producing complement fragments C5a and C3a which are able to recruit and activate immune cells. Complement activation may contribute to pain after inflammation and injury. In this study, we examined whether C5a and C3a elicit nociception when injected into mouse hind paws\nin vivo, and whether C5a and C3a activate and/or sensitize mechanosensitive nociceptors when applied on peripheral terminals\nin vitro. We also examined the dorsal root ganglia (DRG) for C5a receptor (C5aR) mRNA and effects of C5a and C3a on intracellular Ca\n2+ concentration ([Ca\n2+]\ni) using Ca\n2+ imaging. Heat hyperalgesia was elicited by intraplantar injection of C5a, and mechanical hyperalgesia by C5a and C3a. After exposure to either C5a or C3a, C-nociceptors were sensitized to heat as evidenced by an increased proportion of heat responsive fibers, lowered response threshold to heat and increased action potentials during and after heat stimulation. A-nociceptors were activated by complement. However, no change was observed in mechanical responses of A- and C-nociceptors after C5a and C3a application. The presence of C5aR mRNA was detected in DRG. C5a and C3a application elevated [Ca\n2+]\ni and facilitated capsaicin-induced [Ca\n2+]\ni responses in DRG neurons. The results suggest a potential role for complement fragments C5a and C3a in nociception by activating and sensitizing cutaneous nociceptors.

Nociception

Nociceptor

Sensitization

Inflammation

Injury

Hyperalgesia

Details

Title: Subtitle: Nociceptive sensitization by complement C5a and C3a in mouse
Creators: Jun Ho Jang - Department of Anesthesia, University of Iowa Hospitals and Clinics, Iowa City, IA, USA
J. David Clark - Department of Anesthesia, Veterans Affairs Palo Alto Healthcare System and Stanford University School of Medicine, Stanford, CA, USA
Xiangqi Li - Department of Anesthesia, Veterans Affairs Palo Alto Healthcare System and Stanford University School of Medicine, Stanford, CA, USA
Matthew S Yorek - Department of Pharmacology, University of Iowa, Iowa City, IA, USA
Yuriy M Usachev - Department of Pharmacology, University of Iowa, Iowa City, IA, USA
Timothy J Brennan - Department of Anesthesia, University of Iowa Hospitals and Clinics, Iowa City, IA, USA
Resource Type: Journal article
Publication Details: Pain (Amsterdam), Vol.148(2), pp.343-352
DOI: 10.1016/j.pain.2009.11.021
PMID: 20031321
PMCID: PMC2814960
NLM abbreviation: Pain
ISSN: 0304-3959
eISSN: 1872-6623
Publisher: Elsevier B.V
Language: English
Date published: 2010
Academic Unit: Pathology; Iowa Neuroscience Institute; Anesthesia; Fraternal Order of Eagles Diabetes Research Center; Neuroscience and Pharmacology; Internal Medicine
Record Identifier: 9984070360902771

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