title: Nerve growth factor selectively decreases activity-dependent conduction slowing in mechano-insensitive C-nociceptors.
abstract: Nerve growth factor (NGF) induces acute sensitization of nociceptive sensory endings and long-lasting hyperalgesia. NGF modulation of sodium channel expression might contribute to neurotrophin-induced hyperalgesia. Here, we investigated NGF-evoked changes of the activity-dependent slowing of conduction in porcine C-fibers. Animals received intradermal injections of NGF (2 μg or 8 μg) or saline in both hind limbs. Extracellular recordings from the saphenous nerves were performed 1 week later. Based on sensory thresholds and electrically induced activity-dependent slowing (ADS) of axonal conduction, C-fibers were classified as mechano-sensitive afferents, mechano-insensitive afferents, cold nociceptors, and sympathetic efferents. NGF (2 μg) increased conduction velocity in C-fibers from 1.0±0.05 m/s to 1.2±0.07 m/s. In mechano-insensitive afferents, NGF (8 μg) reduced activity-dependent slowing of conduction, from 5.3±0.2% to 3.2±0.5% (0.125-0.5 Hz stimulation) and from 28.5±1.3% to 20.9±1.9% (2 Hz stimulation), such that ADS no longer differentiated between mechano-sensitive and mechano-insensitive fibers. Accordingly, the number of fibers with pronounced ADS decreased but more units with pronounced ADS were mechano-sensitive. Spontaneously active C-fibers were increased above the control level (1%) by NGF 8 μg (8%). The results demonstrate that NGF changes the functional axonal characteristics of mechano-insensitive C-fibers and enhances spontaneous activity thereby possibly contributing to hyperalgesia.
authors.affiliation: Department of Anesthesiology Mannheim, Heidelberg University, Mannheim, Germany Department of Neurosurgery, Johns Hopkins University, Baltimore, MD, USA Department of Mathematics and Computer Science, Bethel University, St. Paul, MN, USA.
authors.forename: Otilia
authors.initials: O
authors.lastname: Obreja
authors.forename: Matthias
authors.initials: M
authors.lastname: Ringkamp
authors.forename: Brian
authors.initials: B
authors.lastname: Turnquist
authors.forename: Michael
authors.initials: M
authors.lastname: Hirth
authors.forename: Elmar
authors.initials: E
authors.lastname: Forsch
authors.forename: Roman
authors.initials: R
authors.lastname: Rukwied
authors.forename: Marlen
authors.initials: M
authors.lastname: Petersen
authors.forename: Martin
authors.initials: M
authors.lastname: Schmelz
mesh_terms: D000818:Animals; D005260:Female; D006801:Humans; D006930:Hyperalgesia / Q000139:chemically induced / Q000503:physiopathology*; D007271:Injections, Intradermal; D008297:Male; D036421:Nerve Fibers, Unmyelinated / Q000187:drug effects / Q000502:physiology*; D020932:Nerve Growth Factor / Q000008:administration & dosage* / Q000502:physiology; D009431:Neural Conduction / Q000187:drug effects / Q000502:physiology*; D009619:Nociceptors / Q000502:physiology*; D034421:Sus scrofa
chemical_list: D020932:Nerve Growth Factor