PMID- 12504600 OWN - NLM STAT- MEDLINE DCOM- 20030321 LR - 20191106 IS - 1044-7431 (Print) IS - 1044-7431 (Linking) VI - 21 IP - 4 DP - 2002 Dec TI - Noxious stimulation induces Trk receptor and downstream ERK phosphorylation in spinal dorsal horn. PG - 684-95 AB - 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. FAU - Pezet, Sophie AU - Pezet S AD - 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 FAU - Malcangio, Marzia AU - Malcangio M FAU - Lever, Isobel J AU - Lever IJ FAU - Perkinton, Michael S AU - Perkinton MS FAU - Thompson, Stephen W N AU - Thompson SW FAU - Williams, Robert J AU - Williams RJ FAU - McMahon, Stephen B AU - McMahon SB LA - eng PT - Journal Article PT - Research Support, Non-U.S. Gov't PL - United States TA - Mol Cell Neurosci JT - Molecular and cellular neurosciences JID - 9100095 RN - 0 (Brain-Derived Neurotrophic Factor) RN - 0 (Plant Extracts) RN - 0 (Plant Oils) RN - EC 2.7.10.1 (Receptor, trkB) RN - EC 2.7.11.24 (Mitogen-Activated Protein Kinases) RN - TYY1MA9BSY (mustard oil) SB - IM MH - Afferent Pathways/drug effects/*metabolism MH - Animals MH - Animals, Newborn MH - Brain-Derived Neurotrophic Factor/*metabolism MH - Male MH - Mitogen-Activated Protein Kinases/drug effects/*metabolism MH - Mustard Plant MH - Nerve Fibers, Unmyelinated/drug effects/metabolism MH - Nociceptors/drug effects/*metabolism MH - Pain/chemically induced/*metabolism/physiopathology MH - Pain Measurement MH - Phosphorylation MH - Physical Stimulation MH - Plant Extracts MH - Plant Oils MH - Posterior Horn Cells/drug effects/*metabolism MH - Precipitin Tests MH - Presynaptic Terminals/drug effects/metabolism MH - Rats MH - Rats, Wistar MH - Receptor, trkB/drug effects/*metabolism MH - Signal Transduction/drug effects/physiology MH - Synaptic Transmission/drug effects/physiology EDAT- 2002/12/31 04:00 MHDA- 2003/03/22 04:00 CRDT- 2002/12/31 04:00 PHST- 2002/12/31 04:00 [pubmed] PHST- 2003/03/22 04:00 [medline] PHST- 2002/12/31 04:00 [entrez] AID - S1044743102912054 [pii] AID - 10.1006/mcne.2002.1205 [doi] PST - ppublish SO - Mol Cell Neurosci. 2002 Dec;21(4):684-95. doi: 10.1006/mcne.2002.1205.