Useful Biomarkers for the Diagnosis of Painful Diabetic Neuropathy (IN1-1.004)

Abstract

Objective: To evaluate the use of skin biopsy in order to corroborate neuropathic pain in PDN by studying IENFD and nerve morphology in distal leg and proximal thigh skin samples. Background Neuropathic pain is a common symptom associated with diabetes. At present, measurement of intraepidermal nerve fiber density (IENFD) in distal skin samples is a standard method for the diagnosis of diabetic neuropathy (DN). However, IENFD measurement is not considered a good indicator for the diagnosis of painful diabetic neuropathy (PDN), a common symptom of early DN. Design/Methods: Skin biopsies were taken from age and sex-matched groups: normal control (n=12), diabetic patients without neuropathy (n=20), diabetic patients with PDN (n=21), and DN patients without pain (n=21). Biopsies were fixed in Zamboni9s solution (2% paraformaldehyde, picric acid) and stained with protein gene product (PGP) 9.5, substance P (SP), and growth associated protein 43 (GAP43). Results: IENFD does not have a diagnostic value for pain in DN. Quantification of IENFD demonstrated no significant difference between matched groups of PDN and DN without pain. In contrast, quantification of regeneration, using GAP43, demonstrated a significant difference between matched groups of PDN and DN without pain. Furthermore, the neuroma densities in proximal skin samples could be used as an indicator for the presence of neuropathic pain in PDN. Morphological studies of skin biopsies from the proximal thigh demonstrated significant presence of axonal swellings or neuromas distributed along the IENF, in the PDN group compared to that of DN without pain. These neuromas are also positive for substance P suggesting they mediate nociception. Conclusions: Axonal swellings or neuromas observed along the epidermal/dermal boundary may be associated with PDN. Morphological differences associated with PDN could demonstrate significant use of skin biopsy for the diagnosis of PDN. Supported by: National Institutes of Health [UO1-DK60994 (ELF); 1K08NS061039 (HTC)] and the Juvenile Diabetes Research Foundation Center. Disclosure: Dr. Cheng has nothing to disclose. Dr. Dauch has nothing to disclose. Dr. Porzio has nothing to disclose. Dr. Yanik has nothing to disclose. Dr. Hsieh has nothing to disclose. Dr. Smith has received personal compensation for activities with Allergan, Baxter Bioscience, Merz, Pfizer and NeurogesX as a consultant. Dr. Smith has received personal compensation in an editorial capacity for serves as the Associate Editor for Education at AAN.com. Dr. Singleton has received personal compensation for activities with Medical Review Institute. Dr. Feldman has received personal compensation for activities with Novartis.