title: Neuropeptide content of peripheral nerve in relation to nerve function in neuropathy.
abstract: OBJECTIVE
  In this study an APAAP (alcalic-phophatase-anti-alcalic-phosphatase) technique was used to distinguish afferent (calcitonin-gene-related-peptide (CGRP) or substance-P-(SP) positive) and autonomic (tyrosin-hydroxylase (TH), neuropeptide Y (NPY) or vasoactive-intestinal-polypeptide- (VIP) positive) nerve fibers in sural nerve biopsy material from patients with moderate sensory neuropathy. A panneuronal marker against protein-gene-product 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 testings, sensitivity to painful mechanical stimulation, axon reflex-mediated flare reaction and sudomotor activity) and nerve pathology.
  
  
  RESULTS
  A high correlation between CGRP and SP (p < 0.00003) and between TH and NPY, respectively, (p < 0.004) was found, but not between afferent and autonomic markers or between specific markers and PGP 9.5. While no correlations between sensory neuropeptides (CGRP and SP) and specific testings of afferent fiber function or between neuropeptide content and clinical data could be demonstrated, there was a significant correlation between the TH content of the sural nerve and the sweat output, stimulated by acetylcholine iontophoresis at the level of the foot (p = 0.019) and upper leg (p = 0.011).
  
  
  CONCLUSIONS
  This study demonstrates the possibility of visualizing subgroups of unmyelinated nerve fibers in sural nerve biopsies selectively with this technique. The density of TH-positive sympathetic nerve fibers, but not the density of afferent c-fibers, is correlated with corresponding results in specific tests of c-fiber function.
authors.affiliation: Department of Neurology, University of Erlangen-Nürnberg, Erlangen, Germany.
authors.forename: A
authors.initials: A
authors.lastname: Bickel
authors.forename: H
authors.initials: H
authors.lastname: Grehl
authors.forename: M
authors.initials: M
authors.lastname: Butz
authors.forename: M
authors.initials: M
authors.lastname: Schmelz
authors.forename: A
authors.initials: A
authors.lastname: Engelhardt
authors.forename: B
authors.initials: B
authors.lastname: Neundörfer
authors.forename: W L
authors.initials: WL
authors.lastname: Neuhuber
authors.forename: H O
authors.initials: HO
authors.lastname: Handwerker
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000704:Analysis of Variance; D001706:Biopsy; D005260:Female; D006801:Humans; D007091:Image Processing, Computer-Assisted; D007124:Immunoenzyme Techniques; D008297:Male; D008875:Middle Aged; D009412:Nerve Fibers / Q000378:metabolism / Q000473:pathology*; D009460:Neurologic Examination; D009479:Neuropeptides / Q000378:metabolism*; D010525:Peripheral Nerves / Q000378:metabolism* / Q000473:pathology / Q000503:physiopathology; D010523:Peripheral Nervous System Diseases / Q000378:metabolism* / Q000473:pathology / Q000503:physiopathology; D012044:Regression Analysis; D013497:Sural Nerve / Q000378:metabolism / Q000473:pathology*
chemical_list: D009479:Neuropeptides