Noxious stimulation induces Trk receptor and downstream ERK phosphorylation in spinal dorsal horn.
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.
Pezet
Sophie
S
Centre for Neuroscience Research, Guy's King's and St. Thomas' School of Biomedical Sciences, King's College London, London SE1, United Kingdom. sophiepezet@kcl.ac.uk
Malcangio
Marzia
M
Lever
Isobel J
IJ
Perkinton
Michael S
MS
Thompson
Stephen W N
SW
Williams
Robert J
RJ
McMahon
Stephen B
SB
D000344:Afferent Pathways / Q000187:drug effects / Q000378:metabolism*; D000818:Animals; D000831:Animals, Newborn; D019208:Brain-Derived Neurotrophic Factor / Q000378:metabolism*; D008297:Male; D020928:Mitogen-Activated Protein Kinases / Q000187:drug effects / Q000378:metabolism*; D009149:Mustard Plant; D036421:Nerve Fibers, Unmyelinated / Q000187:drug effects / Q000378:metabolism; D009619:Nociceptors / Q000187:drug effects / Q000378:metabolism*; D010146:Pain / Q000139:chemically induced / Q000378:metabolism* / Q000503:physiopathology; D010147:Pain Measurement; D010766:Phosphorylation; D010812:Physical Stimulation; D010936:Plant Extracts; D010938:Plant Oils; D020671:Posterior Horn Cells / Q000187:drug effects / Q000378:metabolism*; D011233:Precipitin Tests; D017729:Presynaptic Terminals / Q000187:drug effects / Q000378:metabolism; D051381:Rats; D017208:Rats, Wistar; D020813:Receptor, trkB / Q000187:drug effects / Q000378:metabolism*; D015398:Signal Transduction / Q000187:drug effects / Q000502:physiology; D009435:Synaptic Transmission / Q000187:drug effects / Q000502:physiology
D019208:Brain-Derived Neurotrophic Factor; D010936:Plant Extracts; D010938:Plant Oils; D020813:Receptor, trkB; D020928:Mitogen-Activated Protein Kinases; C027793:mustard oil