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Supraspinal Brain-Derived Neurotrophic Factor Signaling: A Novel Mechanism for Descending Pain Facilitation

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Guo, Wei, Robbins, Meredith T., Wei, Feng, Zou, Shiping, Dubner, Ronald, Ren, Ke·2006·The Journal of Neuroscience

DOI 10.1523/jneurosci.3686-05.2006PMC PMC6674294

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Abstract

In the adult mammalian brain, brain-derived neurotrophic factor (BDNF) is critically involved in long-term synaptic plasticity. Here, we show that supraspinal BDNF-tyrosine kinase receptor B (TrkB) signaling contributes to pain facilitation. We show that BDNF-containing neurons in the periaqueductal gray (PAG), the central structure for pain modulation, project to and release BDNF in the rostral ventromedial medulla (RVM), a relay between the PAG and spinal cord. BDNF in PAG and TrkB phosphorylation in RVM neurons are upregulated after inflammation. Intra-RVM sequestration of BDNF and knockdown of TrkB by RNA interference attenuate inflammatory pain. Microinjection of BDNF (10-100 fmol) into the RVM facilitates nociception, which is dependent on NMDA receptors (NMDARs). In vitro studies with RVM slices show that BDNF induces tyrosine phosphorylation of the NMDAR NR2A subunit in RVM via a signal transduction cascade involving IP(3), PKC, and Src. The supraspinal BDNF-TrkB signaling represents a previously unknown mechanism underlying the development of persistent pain. Our findings also caution that application of BDNF for recovery from CNS disorders could lead to undesirable central pain.

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Authors: Guo, W., Robbins, M. T., Wei, F., Zou, S., Dubner, R., & Ren, K.
Affiliations: University of Maryland, Baltimore (US)
Corresponding author: Ren, Ke
ORCID: Guo, Wei
Ren, Ke
Venue: The Journal of Neuroscience
Publisher: Society for Neuroscience
Published: 2006-01-04
Volume: 26
Issue: 1
Pages: 126-137
ISSN: 0270-6474 (ISSN-L)
1529-2401
DOI: 10.1523/jneurosci.3686-05.2006
PMC: PMC6674294
OpenAlex: W2131110619
Cited by: 192
References: 52
Citations by year: 2026: 5 · 2025: 4 · 2024: 9 · 2023: 6 · 2022: 6 · 2021: 5 · 2020: 7 · 2019: 11 · 2018: 5 · 2017: 7 · 2016: 11 · 2015: 7 · 2014: 17 · 2013: 20 · 2012: 11
FWCI: 9.08
Type: journal article
Language: en
Open access: hybrid
doi.org
Licence: cc-by-nc-sa
creativecommons.org/licenses/by-nc-sa/4.0/ (vor, 181 d)
Locations: Journal of Neuroscience (publishedVersion, cc-by-nc-sa)
PubMed Central (publishedVersion)
PubMed (publishedVersion)
Funders: National Institutes of Health
National Institute on Drug Abuse (DA10275, R01DA010275)
National Institute of Dental and Craniofacial Research (DE 11964, R01DE011964)
Topics: Health Sciences › Medicine › Physiology (medical) › Pain Mechanisms and Treatments
Health Sciences › Medicine › Anesthesiology and Pain Medicine › Pain Management and Treatment
Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Nerve injury and regeneration
Keywords: brain-derived neurotrophic factor, TrkB receptor, descending facilitation, periaqueductal gray, rostral ventromedial medulla, inflammatory pain, NMDA receptor, NR2A subunit, chronic pain, central sensitization, IP3 signaling, protein kinase C, Src kinase, nociception, central pain
MeSH terms: Animals, Male, Medulla Oblongata, Pain, Pain Measurement, Pyramidal Tracts, Signal Transduction, Rats, Sprague-Dawley, Brain-Derived Neurotrophic Factor, Receptor, trkB, Rats

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Supraspinal Brain-Derived Neurotrophic Factor Signaling: A Novel Mechanism for Descending Pain Facilitation

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