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 language | English (US) |
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Pages (from-to) | 1976-1989 |
Number of pages | 14 |
Journal | Glia |
Volume | 65 |
Issue number | 12 |
DOIs | |
State | Published - Dec 2017 |
Bibliographical note
Publisher Copyright:© 2017 Wiley Periodicals, Inc.
Keywords
- calcium imaging
- neuroimmune
- pain