title: trkA is expressed in nociceptive neurons and influences electrophysiological properties via Nav1.8 expression in rapidly conducting nociceptors.
abstract: 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 (Aalpha/beta) as in more slowly conducting (Adelta and C) nociceptors. All Aalpha/beta low-threshold mechanoreceptors (LTMs) are trkA negative, although weak but detectable trkA is present in some C and Adelta LTMs. NGF can influence electrophysiological properties of DRG neurons, probably by binding to trkA. We found positive correlations for single identified Aalpha/beta (but not C or Adelta) 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 Aalpha/beta (notCorAdelta) nociceptors, trkA intensity is inversely correlated with conduction velocity. Similar relationships, again only in Aalpha/beta nociceptors, between electrophysiological properties and trkA expression exist for sodium channel Nav1.8 but not Nav1.9 immunoreactivities. These findings suggest that in Aalpha/beta 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.
authors.affiliation: Department of Physiology, Medical School, University of Bristol, Bristol BS8 1TD, United Kingdom.
authors.forename: Xin
authors.initials: X
authors.lastname: Fang
authors.forename: Laiche
authors.initials: L
authors.lastname: Djouhri
authors.forename: Simon
authors.initials: S
authors.lastname: McMullan
authors.forename: Carol
authors.initials: C
authors.lastname: Berry
authors.forename: Kenji
authors.initials: K
authors.lastname: Okuse
authors.forename: Stephen G
authors.initials: SG
authors.lastname: Waxman
authors.forename: Sally N
authors.initials: SN
authors.lastname: Lawson
mesh_terms: D000200:Action Potentials / Q000187:drug effects / Q000502:physiology*; D000818:Animals; D002452:Cell Count / Q000379:methods; D048429:Cell Size; D003952:Diagnostic Imaging / Q000379:methods; D005260:Female; D005727:Ganglia, Spinal / Q000166:cytology*; D007150:Immunohistochemistry / Q000379:methods; D066298:In Vitro Techniques; D007546:Isoquinolines; D062559:NAV1.8 Voltage-Gated Sodium Channel; D062558:NAV1.9 Voltage-Gated Sodium Channel; D009413:Nerve Fibers, Myelinated / Q000502:physiology; D036421:Nerve Fibers, Unmyelinated / Q000502:physiology; D009419:Nerve Tissue Proteins / Q000378:metabolism*; D009431:Neural Conduction / Q000502:physiology / Q000528:radiation effects; D009474:Neurons / Q000145:classification / Q000187:drug effects / Q000502:physiology*; D009479:Neuropeptides / Q000502:physiology; D009619:Nociceptors / Q000502:physiology*; D009942:Organometallic Compounds; D009943:Organophosphorus Compounds; D051381:Rats; D017208:Rats, Wistar; D020917:Receptor, trkA / Q000378:metabolism*; D026941:Sodium Channel Blockers / Q000494:pharmacology; D015222:Sodium Channels / Q000378:metabolism* / Q000502:physiology; D018709:Statistics, Nonparametric; D013779:Tetrodotoxin / Q000494:pharmacology
chemical_list: D007546:Isoquinolines; D062559:NAV1.8 Voltage-Gated Sodium Channel; D062558:NAV1.9 Voltage-Gated Sodium Channel; D009419:Nerve Tissue Proteins; D009479:Neuropeptides; D009942:Organometallic Compounds; D009943:Organophosphorus Compounds; C568319:Scn10a protein, rat; C113705:Scn11a protein, rat; D026941:Sodium Channel Blockers; D015222:Sodium Channels; C066850:Cascade Blue; D013779:Tetrodotoxin; C017475:lucifer yellow; D020917:Receptor, trkA