TY - JOUR
T1 - trkA is expressed in nociceptive neurons and influences electrophysiological properties via Nav1.8 expression in rapidly conducting nociceptors
AU - Fang, Xin
AU - Djouhri, Laiche
AU - McMullan, Simon
AU - Berry, Carol
AU - Okuse, Kenji
AU - Waxman, Stephen G.
AU - Lawson, Sally N.
PY - 2005/5/11
Y1 - 2005/5/11
N2 - To test the hypothesis that trkA (the high-affinity NGF receptor) is selectively expressed in nociceptive dorsal root ganglion (DRG) neurons, we examined the intensity of trkA immunoreactivity in single dye-injected rat DRG neurons, the sensory receptor properties of which were identified in vivo with mechanical and thermal stimuli. We provide the first evidence in single identified neurons that strong trkA expression in DRGs is restricted to nociceptive neurons, probably accounting for the profound influence of NGF on these neurons. Furthermore, we demonstrate that trkA expression is as high in rapidly conducting (Aα/β) as in more slowly conducting (Aδ and C) nociceptors. All Aα/β low-threshold mechanoreceptors (LTMs) are trkA negative, although weak but detectable trkA is present in some C and Aδ LTMs. NGF can influence electrophysiological properties of DRG neurons, probably by binding to trkA. We found positive correlations for single identified Aα/β (but not C or Aδ) nociceptors between trkA immunocytochemical intensity and electrophysiological properties typical of nociceptors, namely long action potential and afterhyperpolarization durations and large action potential amplitudes. Furthermore, for Aα/β (not C or Aδ) nociceptors, trkA intensity is inversely correlated with conduction velocity. Similar relationships, again only in Aα/β nociceptors, between electrophysiological properties and trkA expression exist for sodium channel Nav1.8 but not Nav1.9 immunoreactivities. These findings suggest that in Aα/β nociceptors, influences of NGF on expression levels of Nav1.8 are related to, and perhaps limited by, expression levels of trkA. This view is supported by a positive correlation between immuno-intensities of trkA and Nav1.8 in A-fiber, but not C-fiber, nociceptors.
AB - To test the hypothesis that trkA (the high-affinity NGF receptor) is selectively expressed in nociceptive dorsal root ganglion (DRG) neurons, we examined the intensity of trkA immunoreactivity in single dye-injected rat DRG neurons, the sensory receptor properties of which were identified in vivo with mechanical and thermal stimuli. We provide the first evidence in single identified neurons that strong trkA expression in DRGs is restricted to nociceptive neurons, probably accounting for the profound influence of NGF on these neurons. Furthermore, we demonstrate that trkA expression is as high in rapidly conducting (Aα/β) as in more slowly conducting (Aδ and C) nociceptors. All Aα/β low-threshold mechanoreceptors (LTMs) are trkA negative, although weak but detectable trkA is present in some C and Aδ LTMs. NGF can influence electrophysiological properties of DRG neurons, probably by binding to trkA. We found positive correlations for single identified Aα/β (but not C or Aδ) nociceptors between trkA immunocytochemical intensity and electrophysiological properties typical of nociceptors, namely long action potential and afterhyperpolarization durations and large action potential amplitudes. Furthermore, for Aα/β (not C or Aδ) nociceptors, trkA intensity is inversely correlated with conduction velocity. Similar relationships, again only in Aα/β nociceptors, between electrophysiological properties and trkA expression exist for sodium channel Nav1.8 but not Nav1.9 immunoreactivities. These findings suggest that in Aα/β nociceptors, influences of NGF on expression levels of Nav1.8 are related to, and perhaps limited by, expression levels of trkA. This view is supported by a positive correlation between immuno-intensities of trkA and Nav1.8 in A-fiber, but not C-fiber, nociceptors.
KW - Action potential
KW - Conduction velocity
KW - Dorsal root ganglion (DRG)
KW - NGF
KW - Pain
KW - Sodium channel
UR - http://www.scopus.com/inward/record.url?scp=18644381918&partnerID=8YFLogxK
U2 - 10.1523/JNEUROSCI.0249-05.2005
DO - 10.1523/JNEUROSCI.0249-05.2005
M3 - Article
C2 - 15888662
AN - SCOPUS:18644381918
VL - 25
SP - 4868
EP - 4878
JO - The Journal of neuroscience : the official journal of the Society for Neuroscience
JF - The Journal of neuroscience : the official journal of the Society for Neuroscience
SN - 0270-6474
IS - 19
ER -