TY - JOUR
T1 - Noxious stimulation induces Trk receptor and downstream ERK phosphorylation in spinal dorsal horn
AU - Pezet, S
AU - Malcangio, M
AU - Lever, I J
AU - Perkinton, M S
AU - Thompson, S W
AU - Williams, R J
AU - McMahon, S B
PY - 2002
Y1 - 2002
N2 - 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
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
UR - http://www.scopus.com/inward/record.url?scp=0036938785&partnerID=8YFLogxK
U2 - 10.1006/mcne.2002.1205
DO - 10.1006/mcne.2002.1205
M3 - Article
VL - 21
SP - 684
EP - 695
JO - Molecular and Cellular Neurosciences
JF - Molecular and Cellular Neurosciences
IS - 4
ER -