• Siddharth Kharkar, Yedatore S Venkatesh, John R Grothusen, Luisa Rojas, and Robert J Schwartzman.
• Department of Neurology, Drexel University College of Medicine, Philadelphia, PA, USA.
• Pain Physician. 2012 May 1;15(3):255-66.

BackgroundAccumulating experimental and clinical evidence supports the hypothesis that complex regional pain syndrome type I (CRPS-I) may be a small fiber neuropathy.ObjectivesTo evaluate the use of commercially available standard biopsy methods to detect intradermal axon pathology in CRPS-I, and to ascertain if these structural changes can explain quantitative sensory testing (QST) findings in CRPS-I.Study DesignRetrospective review of charts and laboratory data.SettingOutpatient clinicMethodsSkin biopsies from 43 patients with CRPS-I were stained with PGP 9.5, and epidermal nerve fiber density, sweat gland nerve fiber density and morphological abnormalities were evaluated. Thirty-five patients had quantitative sensory testing.ResultsAlterations in skin innervation were seen in approximately 20% of CRPS-I patients with commercial processing. There were no patient characteristics, including duration of disease, that predicted a decreased epidermal nerve fiber density (ENFD). There was no consistent relationship between QST changes and ENFD measured by standard commercial skin biopsy evaluation procedures.LimitationsCommercial processing of tissue does not utilize stereologic quantitative analysis of nerve fiber density. Biopsy material is utilized from a proximal and distal source only, and differences in denervation of a partial nerve territory may be missed. The functional attributes of small fibers cannot be assessed.ConclusionsThe negative results indicate that CRPS-I may be associated with changes in the ultramicroscopic small fiber structure that cannot be visualized with commercially available techniques. Alternatively, functional rather than structural alterations of small fibers or pathological changes at a more proximal site such as the spinal cord or brain may be responsible for the syndrome.

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