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Updated: Jun 17, 2026

The Spared Nerve Injury (SNI) Model of Induced Mechanical Allodynia in Mice
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Nociceptive sensitization by complement C5a and C3a in mouse.

Jun Ho Jang1, David J Clark, Xiangqi Li

  • 1Department of Anesthesia, University of Iowa Hospitals and Clinics, Iowa City, IA, USA Department of Anesthesia, Veterans Affairs Palo Alto Healthcare System and Stanford University School of Medicine, Stanford, CA, USA Department of Pharmacology, University of Iowa, Iowa City, IA, USA Graduate Program of Neuroscience, University of Iowa, Iowa City, IA, USA.

Pain
|December 25, 2009
PubMed
Summary
This summary is machine-generated.

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Complement fragments C5a and C3a, produced during injury, activate immune cells and may cause pain. This study shows these fragments activate and sensitize pain-sensing neurons, suggesting a role in nociception.

Area of Science:

  • Immunology
  • Neuroscience
  • Pain Research

Background:

  • Complement system activation increases inflammation and may contribute to pain post-injury.
  • Complement fragments C5a and C3a are key mediators in recruiting and activating immune cells.

Purpose of the Study:

  • To investigate if C5a and C3a elicit nociception in vivo.
  • To determine if C5a and C3a activate or sensitize peripheral nociceptors in vitro.
  • To examine C5a receptor (C5aR) mRNA in dorsal root ganglia (DRG) and C5a/C3a effects on intracellular calcium ([Ca(2+)](i)).

Main Methods:

  • In vivo injection of C5a and C3a into mouse hind paws.
  • In vitro application of C5a and C3a to peripheral nociceptor terminals.
  • Calcium imaging of DRG neurons to measure [Ca(2+)](i) changes.

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  • RT-PCR to detect C5aR mRNA in DRG.

    • Main Results:

    • C5a induced heat hyperalgesia; C5a and C3a induced mechanical hyperalgesia.
    • C5a and C3a sensitized C-nociceptors to heat and activated A-nociceptors.
    • C5aR mRNA was detected in DRG; C5a and C3a increased [Ca(2+)](i) in DRG neurons.

    Conclusions:

    • Complement fragments C5a and C3a play a role in pain signaling.
    • These fragments activate and sensitize cutaneous nociceptors, contributing to hyperalgesia.
    • Targeting complement fragments may offer novel pain management strategies.