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BDNF in Neuropathic Pain; the Culprit that Cannot be Apprehended
1Neuroscience and Mental Health Institute and Department of Pharmacology, University of Alberta, Edmonton, Canada.
Neuroscience
|February 28, 2024
Summary
Brain-derived neurotrophic factor (BDNF) is crucial for neuropathic pain in males, not females. Microglia-derived BDNF increases neuronal excitability, contributing to pain and associated mood disorders.
Area of Science:
- Neuroscience
- Pain Research
- Molecular Biology
Background:
- Neuropathic pain involves complex changes in neuronal excitability.
- Brain-derived neurotrophic factor (BDNF) is implicated in pain signaling.
- Sex differences exist in pain perception and mechanisms.
Purpose of the Study:
- To elucidate the role of BDNF in neuropathic pain, particularly sex-dependent mechanisms.
- To investigate the cellular sources and downstream effects of BDNF in pain pathways.
- To explore the involvement of BDNF in supra-spinal pain processing and comorbidities.
Main Methods:
- Analysis of molecular mediators released from injured nerves.
- Investigation of microglial activation and purinergic receptor expression (P2X4).
- Assessment of BDNF's impact on neuronal excitability and synaptic function.
- Examination of effects on GABAergic inhibition and NMDA receptor activity.
- Exploration of astrocyte-derived cytokine release.
- Evaluation of pain processing in thalamus, cortex, and mesolimbic system.
Main Results:
- BDNF is essential for neuropathic pain onset and maintenance in males, but not females.
- Microglia, activated by CSF-1 and expressing P2X4 receptors, release BDNF.
- Microglial BDNF enhances excitatory and reduces inhibitory neuronal signaling, alters chloride gradients, and increases NMDA receptor function.
- BDNF also promotes pro-inflammatory cytokine release from astrocytes, contributing to dorsal horn hyperexcitability.
- Peripheral nerve injury affects supra-spinal structures, with evidence suggesting microglial BDNF involvement in males.
Conclusions:
- Microglial-derived BDNF is a key driver of neuropathic pain in males by increasing neuronal excitability.
- Sex differences in pain mechanisms are evident, with T-lymphocytes potentially playing a role in females.
- While BDNF is central to pain, neither BDNF nor its receptor TrkB are currently viable therapeutic targets.
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