Neuropeptide content of peripheral nerve in relation to nerve function in neuropathy

Objective: In this study an APAAP (alcalic-phophatase-anti-alcalic-phosphat ase) technique was used to distinguish afferent (calcitonin-gene-related-pe ptide (CGRP) or substance-P-(SP) positive) and autonomic (tyrosin-hydroxyla se (TH), neuropeptide Y (NPY) or vasoactive-intestinal-polypeptide- (VIP) p ositive) nerve fibers in sural nerve biopsy material from patients with mod erate sensory neuropathy. A pan neuronal marker against protein-gene-produc t 9.5 (PGP 9.5) was used for detection of the total amount of nerve fibers. Second aim was to analyze possible correlations between the impairment in tests for the function of unmyelinated fibers (i.e. thermal threshold testi ngs, sensitivity to painful mechanical stimulation, axon reflex-mediated fl are reaction and sudomotor activity) and nerve pathology. Results: A high c orrelation between CGRP and SP (p < 0.00003) and between TH and NPY, respec tively, (p < 0.004) was found, but not between afferent and autonomic marke rs or between specific markers and PGP 9.5. While no correlations between s ensory neuropeptides (CGRP and SP) and specific testings of afferent fiber function or between neuropeptide content and clinical data could be demonst rated, there was a significant correlation between the TH content of the su ral nerve and the sweat output, stimulated by acetylcholine iontophoresis a t the level of the foot (p = 0.019) and upper leg (p = 0.011). Conclusion: This study demonstrates the possibility of visualizing subgroups of unmyeli nated nerve fibers in sural nerve biopsies selectively with this technique. The density of TH-positive sympathetic nerve fibers, but not the density o f afferent c-fibers, is correlated with corresponding results in specific t ests of c-fiber function.