Abstract
Several lines of evidence suggest that the brain-derived neurotrophic factor (BDNF) acts as central pain neuromodulator. We examined the ability of different types of peripheral stimulation to activate the BDNF high-affinity receptor, TrkB, in the spinal cord. We found that noxious chemical, mechanical, or thermal stimuli, but not innocuous stimuli, caused Trk phosphorylation in the spinal cord. These changes were rapid and transient and restricted to somatotopically appropriate spinal segments. We observed, both in vitro and in vivo, that exogenous BDNF induced a rapid activation of ERK, a signaling kinase important in the development of acute pain. Finally, we found that sequestering BDNF in vivo with a TrkB-IgG fusion molecule significantly reduced the activation of ERK evoked by noxious stimulation. These data suggest that BDNF, once released with activity from primary afferent nociceptors, exerts a neuromodulatory role in pain processing through stimulation of postsynaptic TrkB receptors and subsequent activation of ERK.
Publication types
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Research Support, Non-U.S. Gov't
MeSH terms
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Afferent Pathways / drug effects
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Afferent Pathways / metabolism*
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Animals
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Animals, Newborn
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Brain-Derived Neurotrophic Factor / metabolism*
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Male
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Mitogen-Activated Protein Kinases / drug effects
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Mitogen-Activated Protein Kinases / metabolism*
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Mustard Plant
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Nerve Fibers, Unmyelinated / drug effects
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Nerve Fibers, Unmyelinated / metabolism
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Nociceptors / drug effects
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Nociceptors / metabolism*
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Pain / chemically induced
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Pain / metabolism*
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Pain / physiopathology
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Pain Measurement
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Phosphorylation
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Physical Stimulation
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Plant Extracts
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Plant Oils
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Posterior Horn Cells / drug effects
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Posterior Horn Cells / metabolism*
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Precipitin Tests
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Presynaptic Terminals / drug effects
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Presynaptic Terminals / metabolism
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Rats
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Rats, Wistar
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Receptor, trkB / drug effects
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Receptor, trkB / metabolism*
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Signal Transduction / drug effects
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Signal Transduction / physiology
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Synaptic Transmission / drug effects
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Synaptic Transmission / physiology
Substances
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Brain-Derived Neurotrophic Factor
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Plant Extracts
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Plant Oils
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Receptor, trkB
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Mitogen-Activated Protein Kinases
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mustard oil