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Cited by 197Pain Mechanisms and TreatmentsNeuroinflammation and Neurodegeneration MechanismsAdenosine and Purinergic Signaling

Brain-derived neurotrophic factor from microglia: a molecular substrate for neuropathic pain

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Trang, Tuan, Beggs, Simon, Salter, Michael W.·2011·Neuron Glia Biology
DOI 10.1017/s1740925x12000087PMC PMC3748035
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Abstract

One of the most significant advances in pain research is the realization that neurons are not the only cell type involved in the etiology of chronic pain. This realization has caused a radical shift from the previous dogma that neuronal dysfunction alone accounts for pain pathologies to the current framework of thinking that takes into account all cell types within the central nervous system (CNS). This shift in thinking stems from growing evidence that glia can modulate the function and directly shape the cellular architecture of nociceptive networks in the CNS. Microglia, in particular, are increasingly recognized as active principal players that respond to changes in physiological homeostasis by extending their processes toward the site of neural damage, and by releasing specific factors that have profound consequences on neuronal function and that contribute to CNS pathologies caused by disease or injury. A key molecule that modulates microglia activity is ATP, an endogenous ligand of the P2 receptor family. Microglia expresses several P2 receptor subtypes, and of these the P2X4 receptor subtype has emerged as a core microglia–neuron signaling pathway: activation of this receptor drives the release of brain-derived neurotrophic factor (BDNF), a cellular substrate that causes disinhibition of pain-transmitting spinal lamina I neurons. Converging evidence points to BDNF from spinal microglia as being a critical microglia–neuron signaling molecule that gates aberrant nociceptive processing in the spinal cord. The present review highlights recent advances in our understanding of P2X4 receptor-mediated signaling and regulation of BDNF in microglia, as well as the implications for microglia–neuron interactions in the pathobiology of neuropathic pain.

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  • Microglia activation may also lead to the release of neurotrophic molecules such as brain-derived neurotrophic factor.

    “Although microglia activation is associated with pro-inflammatory cytokine production, activation may also lead to the release of neurotrophic molecules such as brain-derived neurotrophic factor (64).”

    From LRRK2 mediates microglial neurotoxicity via NFATc2 in rodent models of synucleinopathies (2020) · cites this paper as [64]

  • Microglia activation is associated with pro-inflammatory cytokine production.

    “Although microglia activation is associated with pro-inflammatory cytokine production, activation may also lead to the release of neurotrophic molecules such as brain-derived neurotrophic factor (64).”

    From LRRK2 mediates microglial neurotoxicity via NFATc2 in rodent models of synucleinopathies (2020) · cites this paper as [64]

    The Introduction describes activated microglia releasing BDNF, but does not say that microglial activation is associated with pro-inflammatory cytokine production. Searches for “pro-inflammatory cytokines” and “cytokine production” found no passage addressing that claim. (LLM, conf=0.72)

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Cited by

Sorted by citations

Authors
Trang, T., Beggs, S., & Salter, M. W.
Affiliations
University of Toronto (CA)
Corresponding author
Salter, Michael W.
ORCID
Venue
Neuron Glia Biology
Publisher
Cambridge University Press (CUP)
Published
2011-02
Volume
7
Issue
1
Pages
99-108
ISSN
  • 1740-925X (ISSN-L)
  • 1741-0533
DOI
10.1017/s1740925x12000087
PMC
PMC3748035
OpenAlex
W2156947921
Cited by
197
References
12
Citations by year
2026: 3 · 2025: 4 · 2024: 7 · 2023: 12 · 2022: 10 · 2021: 15 · 2020: 12 · 2019: 12 · 2018: 17 · 2017: 15 · 2016: 21 · 2015: 16 · 2014: 31 · 2013: 20 · 2012: 1
FWCI
1.84
Type
journal article
Language
en
Open access
Licence
www.cambridge.org/core/terms (unspecified, 476 d)
Locations
  • Neuron Glia Biology (publishedVersion)
  • PubMed (publishedVersion)
  • Europe PMC (PubMed Central) (acceptedVersion)
  • PubMed Central (acceptedVersion)
  • UCL Discovery (University College London) (submittedVersion)
Funders
Canadian Institutes of Health Research (11219_6, MT-11219)
Topics
  • Health Sciences › Medicine › Physiology › Pain Mechanisms and Treatments
  • Life Sciences › Neuroscience › Neurology › Neuroinflammation and Neurodegeneration Mechanisms
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Physiology › Adenosine and Purinergic Signaling
Keywords
brain-derived neurotrophic factor, microglia, neuropathic pain, P2X4 receptor, ATP, nociception, chronic pain
MeSH terms
Animals, Central Nervous System, Humans, Neuralgia, Cytokines, Microglia, Brain-Derived Neurotrophic Factor, Receptors, Purinergic P2X

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