ArticlePain2019
Mechanisms underlying mechanical sensitization induced by complement C5a: the roles of macrophages, TRPV1, and calcitonin gene-related peptide receptors.
Article in Pain, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 26 papers.
What it found
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
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Who cites it
26 citing papers in PubMed, 41 citations in OpenAlex.
- From the Perspective of the Peripheral Sensory Nervous System: The Role of Vitamin D in Neurogenic Inflammatory Skin Disorders.Acta physiologica (Oxford, England) · 2026Review
- Temporal regulation of macrophage polarization by abnormally innervated CGRP + Sensory nerves following spinal cord injury.Cellular and molecular life sciences : CMLS · 2026Review
- Mitochondrial CaCell calcium · 2025Article
- C5a in the peripheral plasma of female fibromyalgia patients is elevated but not related to pain sensitivity as in healthy controls.Scientific reports · 2025Article
- Article
- Sustained pain and macrophage infiltration in a mouse muscle contusion model.Muscle & nerve · 2024Article
- Pathophysiology of Pain and Mechanisms of Neuromodulation: A Narrative Review (A Neuron Project).Journal of pain research · 2024Review
- Macrophages and microglia in inflammation and neuroinflammation underlying different pain states.Medical review (2021) · 2023Article
- Dermal macrophages set pain sensitivity by modulating the amount of tissue NGF through an SNX25-Nrf2 pathway.Nature immunology · 2023Article
- Article
- Adolescent ethanol drinking promotes hyperalgesia, neuroinflammation and serotonergic deficits in mice that persist into adulthood.Brain, behavior, and immunity · 2023Article
- Central and peripheral analgesic active components of triterpenoid saponins fromFrontiers in pharmacology · 2023Article
- The role of TRPV1 in RA pathogenesis: worthy of attention.Frontiers in immunology · 2023Review
- Shared Genetic Regulatory Networks Contribute to Neuropathic and Inflammatory Pain: Multi-Omics Systems Analysis.Biomolecules · 2022Article
- Ehrlich Tumor Induces TRPV1-Dependent Evoked and Non-Evoked Pain-like Behavior in Mice.Brain sciences · 2022Article
- Mechanical Stretch Induced Skin Regeneration: Molecular and Cellular Mechanism in Skin Soft Tissue Expansion.International journal of molecular sciences · 2022Review
- Peripheral mechanisms of chronic pain.Medical review (2021) · 2022Review
- Visualization of trigeminal ganglion sensory neuronal signaling regulated by Cdk5.Cell reports · 2022Article
- Association of Pain with Plasma C5a in Patients with Neuromyelitis Optica Spectrum Disorders During Remission.Neuropsychiatric disease and treatment · 2022Article
- Complement C3 Aggravates Post-epileptic Neuronal Injury Via Activation of TRPV1.Neuroscience bulletin · 2021Article
Corrections and comments
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Authors and funding
5 authors at 2 institutions in 1 country.
Funding
Abstract
The complement system significantly contributes to the development of inflammatory and neuropathic pain, but the underlying mechanisms are poorly understood. Recently, we identified the signaling pathway responsible for thermal hypersensitivity induced by the complement system component C5a. Here, we examine the mechanisms of another important action of C5a, induction of mechanical hypersensitivity. We found that intraplantar injection of C5a produced a dose-dependent mechanical sensitization and that this effect was blocked by chemogenetic ablation of macrophages in both male and female mice. Knockout of TRPV1 or pretreatment with the TRPV1 antagonists, AMG9810 or 5'-iodoresiniferatoxin (5'-IRTX), significantly reduced C5a-induced mechanical sensitization. Notably, local administration of 5'-IRTX 90 minutes after C5a injection resulted in a slow, but complete, reversal of mechanical sensitization, indicating that TRPV1 activity was required for maintaining C5a-induced mechanical hypersensitivity. This slow reversal suggests that neurogenic inflammation and neuropeptide release may be involved. Indeed, pretreatment with a calcitonin gene-related peptide (CGRP) receptor antagonist (but not an antagonist of the neurokinin 1 receptor) prevented C5a-induced mechanical sensitization. Furthermore, intraplantar injection of CGRP produced significant mechanical sensitization in both wild-type and TRPV1 knockout mice. Taken together, these findings suggest that C5a produces mechanical sensitization by initiating macrophage-to-sensory-neuron signaling cascade that involves activation of TRPV1 and CGRP receptor as critical steps in this process.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the Socratic graph.