Complement 3a receptor in dorsal horn microglia mediates pronociceptive neuropeptide signaling

Suzanne Doolen, Jennifer Cook, Maureen S Riedl, Kelley F Kitto, Shinichi Kohsaka, Christopher N Honda, Carolyn A Fairbanks, Bradley K. Taylor, Lucy Vulchanova

Research output: Contribution to journalArticle

5 Citations (Scopus)

Abstract

The complement 3a receptor (C3aR1) participates in microglial signaling under pathological conditions and was recently shown to be activated by the neuropeptide TLQP-21. We previously demonstrated that TLQP-21 elicits hyperalgesia and contributes to nerve injury-induced hypersensitivity through an unknown mechanism in the spinal cord. Here we determined that this mechanism requires C3aR1 and that microglia are the cellular target for TLQP-21. We propose a novel neuroimmune signaling pathway involving TLQP-21-induced activation of microglial C3aR1 that then contributes to spinal neuroplasticity and neuropathic pain. This unique dual-ligand activation of C3aR1 by a neuropeptide (TLQP-21) and an immune mediator (C3a) represents a potential broad-spectrum mechanism throughout the CNS for integration of neuroimmune crosstalk at the molecular level.

Original languageEnglish (US)
Pages (from-to)1976-1989
Number of pages14
JournalGLIA
Volume65
Issue number12
DOIs
StatePublished - Dec 1 2017

Fingerprint

Complement C3a
Complement Receptors
Microglia
Neuropeptides
Neuronal Plasticity
Hyperalgesia
Neuralgia
Spinal Cord
Hypersensitivity
Ligands
Wounds and Injuries
Spinal Cord Dorsal Horn

Keywords

  • calcium imaging
  • neuroimmune
  • pain

Cite this

Complement 3a receptor in dorsal horn microglia mediates pronociceptive neuropeptide signaling. / Doolen, Suzanne; Cook, Jennifer; Riedl, Maureen S; Kitto, Kelley F; Kohsaka, Shinichi; Honda, Christopher N; Fairbanks, Carolyn A; Taylor, Bradley K.; Vulchanova, Lucy.

In: GLIA, Vol. 65, No. 12, 01.12.2017, p. 1976-1989.

Research output: Contribution to journalArticle

Doolen, Suzanne ; Cook, Jennifer ; Riedl, Maureen S ; Kitto, Kelley F ; Kohsaka, Shinichi ; Honda, Christopher N ; Fairbanks, Carolyn A ; Taylor, Bradley K. ; Vulchanova, Lucy. / Complement 3a receptor in dorsal horn microglia mediates pronociceptive neuropeptide signaling. In: GLIA. 2017 ; Vol. 65, No. 12. pp. 1976-1989.
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