Funktionelle Untersuchungen von Ionenkanälen in unmyelinisierten Axonen des Menschen

Abstract

Clinical assessment of large fibre neuropathy is a routine neurological procedure. The clinical assessment of small fibre function however is far less well established and as a consequence pharmaceutical therapies for small fibre neuropathies often comprise sequential trials with different medications until one works. To refine the diagnosis and treatment of small fibre neuropathies a fuller understanding of the physiological and pharmacological profile of human unmyelinated axons is required. To this end we have adopted the in vitro preparation of human sural nerve segments first described by Lambert and Dyck (1) and developed techniques to examine the excitability and chemosensitivity of human unmyelinated axons. Individual nerve fascicles were extracted from sural nerve segments taken at biopsy or after amputation and mounted between stimulating and recording suction electrodes in a small organ bath. The excitability of all unmyelinated axons within an individual fascicle was determined by monitoring the amplitude and latency of the compound C fibre action potential response to constant current electrical stimulation. Using threshold tracking techniques it is possible to monitor multiple excitability parameters (2) of human C-fibres during the application of pharmacological agents to the bathing solution. We have used this in vitro preparation to examine the effect of specific inflammatory mediators on the excitability of human C fibres as well as the ability of several compounds used in the clinical treatment of neuropathic pain to influence the effects of such mediators.