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Acta Physiologica 2011; Volume 201, Supplement 682
The 90th Annual Meeting of The German Physiological Society
3/26/2011-3/29/2011
Regensburg, Germany
DIFFERENTIAL EFFECTS OF LIDOCAINE AND A SPECIFIC NAV1.7 BLOCKER ON THE CONDUCTIVE PROPERTIES OF C-FIBERS, IN PIG SKIN
Abstract number: O87
*Hirth1 M., *Obreja1 O., Ringkamp2 M., Rukwied1 R., Nystroem3 J.-E., Raboisson3 P., Hagglof3 B., *Schmelz1 M.
Mutations of the axonal sodium channel Nav1.7 can generate either a syndrom of congenital indifference to pain (CIP) or neuropathic conditions like erythromelalgia. Since microneurographic recordings in erythromelalgia patients identified specific changes in the axonal characteristics of C-nociceptors, Nav1.7 emerges as an attractive target for chronic pain treatment. However, pharmacological interventions are limited in human microneurography. We have found that human and porcine nociceptive and non-nociceptive C-fiber classes correlated in both distribution and conduction characteristics, thus establishing a human-like animal model suitable for pharmacological investigations. Here we compared the axonal effects of lidocaine (a non-specific local anesthetic) and of a specific Nav1.7 blocker (developed by Astra-Zeneca). Saline solution served as control. Single-fiber extracellular recordings from porcine saphenous nerves were performed. We classified C-nociceptors as mechano-sensitive and mechano-insensitive, according to their mechanical responsiveness and amount of activity-dependent slowing (ADS) of conduction velocity. After characterization, 100ml of either lidocaine 0.1% or Nav1.7 blocker (20mM) were injected intradermally at the stimulation site. Axonal and sensory testing was repeated after injection. Lidocaine increased electrical thresholds and resting conduction latencies and decreased ADS in 6 mechano-insensitive and 7 mechano-sensitive C-nociceptors. In contrast, the specific Nav1.7 blocker preferentially affected mechano-insensitive nociceptors (n= 4), while sparing mechano-sensitive nociceptors (n= 4). Accordingly, Nav1.7 blocker rendered all mechano-insensitive units more susceptible to a conduction block. Saline did not alter conductive properties of any porcine C-fibers. We conclude that nerve conduction in mechano-insensitive nociceptors in pig skin depends on the presence of functional axonal Nav1.7 channels.
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Acta Physiologica 2011; Volume 201, Supplement 682 :O87