The aim of this project is to determine whether painful peripheral neuropathies in humans are associated with abnormalities of spinal cord neuropeptide synthesis and neuropeptide receptor regulation. Such abnormalities have been detected in rats with an experimental version of painful peripheral neuropathy; the question addressed in this project is whether or not similar abnormalities occur in humans. Autopsy specimens (donated by patients or the family of the deceased) from spinal cord will be obtained as soon as possible after death, with particular care taken to correctly identify the spinal segments associated with the peripheral location of the pain symptoms. The specimens will be divided at the time of autopsy into two samples. One sample will be processed with immunohistochemical staining for the presence of 8 neuropeptides; the other sample will be processed for the autoradiographic demonstration of receptor binding for 5 peptide ligands. Tissue donors with pre-morbid history of reflex sympathetic dystrophy or causalgia will be the primary focus of this work because of the similarity between the symptoms and antecedents of these conditions and those of the experimental model. However, the study will also accept material from patients with other kinds of painful peripheral neuropathy (e.g., post- herpetic neuralgia and diabetic neuralgia). This is justified because of evidence indicating that neuropathies with different etiologies may nevertheless share fundamentally similar pathogenic mechanisms. In all cases, material will be accepted only if the abnormal pain symptoms were unilateral; this will allow side-to-side comparisons for the identification of abnormalities.
