A novel noninvasive technique was applied to measure velocity within slow conducting axons in the distal extreme of the sciatic nerve (i.e., digital nerve) in a rat model. The technique is based on the extraction of rectified multiple unit activity (MUA) from in vivo whole nerve compound responses. This method reliably identifies compound action potentials in thinly myelinated fibers conducting at a range of 9–18？m/s ( axons), as well as in a subgroup of unmyelinated C fibers conducting at approximately 1-2？m/s. The sensitivity of the method to C-fiber conduction was confirmed by the progressive decrement of the responses in the 1-2？m/s range over a 20-day period following the topical application of capsaicin (ANOVA ). Increasing the frequency of applied repetitive stimulation over a range of 0.75？Hz to 6.0？Hz produced slowing of conduction and a significant decrease in the magnitude of the compound C-fiber response (ANOVA ). This technique offers a unique opportunity for the noninvasive, repeatable, and quantitative assessment of velocity in the subsets of and C fibers in parallel with the evaluation of fast nerve conduction. 1. Introduction The evaluation of peripheral nerve conduction velocity (NCV) (CAP: capsaicin, HFRS: high frequency repetitive stimulation, MUA: multiple unit activity, NCV: nerve conduction velocity, NFD: nerve fiber density, and SFN: small fiber neuropathy) is a well-established and highly utilized procedure for the assessment of the pattern, symmetry and extent of neuropathy in both pre-clinical and clinical studies [1–4]. When properly performed, NCV provides a sensitive, objective, and specific index of the onset and progression of multiple forms of nerve damage. C fibers make up the majority of fibers in some nerve segments; however, standard NCV measures are only sensitive to activity in fast conducting, heavily myelinated axons. The in vivo assessment of conduction in small diameter axons is a formidable task due to the requirement of high-threshold stimulation, asynchronous, slow conduction and phase cancellation with distance [5]. The inability to assess conduction, in thinly myelinated Aδ axons or in unmyelinated C fibers is a severe limitation of NCV procedures. There is a growing recognition that many forms of idiopathic small fiber neuropathies (SFNs) may have been poorly diagnosed and their prevalence underestimated due, in part, to a lack of sensitive, non-invasive measures of this condition [5–10]. SFN can result in pain, paresthesias, abnormal thermal sensitivity, and various autonomic dysfunctions. Emerging data
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