Peripheral nerve pathology in patients with severely affected complex regional pain syndrome type I

Complex regional pain syndrome type I (CRPS-I) is a chronic pain syndrome with no clinical evidence of nerve injury; however, recently, changes in muscle tissue have been found in case of CRPS-I. Our aim was to search for histological changes in peripheral nerves of amputated limbs from patients with therapy-resistant CRPS-I that could justify muscle tissue changes. Fifteen patients with CRPS-I (duration >1 year) were included. Multiple nerve samples were taken from upper (n=4) and lower (n=11) amputated limbs. Histological changes (signs of nerve fiber loss and regeneration), fiber diameters, fiber diameter distribution, and fiber density were studied through microscopy and morphometry. Samples from three healthy sural nerves were used as control data as well as data from the literature. All patients (93% of tissue samples) showed histological signs of nerve fiber loss and fiber regeneration, varying in severity. No specific preference was found for any nerve or the location within the nerve. Sural nerves showed loss of especially larger nerve fibers (>12 μm) in comparison with control data. Sympathectomy did not influence this finding. The morphometric results of the other nerves are more difficult to interpret because of the absence of good-quality control data from the literature. However, the percentages of nerve fibers greater than 12 μm seem to lie within the normal range. Besides the known pathology of thin nerve fibers innervating the skin or blood vessels in CRPS-I, this study also shows pathological changes more proximal in the nerves, especially in the sural nerve.