Peptides and neuromas: calcitonin gene-related peptide, substance P, and mast cells in a mechanosensitive human sural neuroma.

We examined and compared a mechanosensitive human sural neuroma and a contralateral sural nerve collected simultaneously from a patient involved in a diabetic neuropathy research protocol. Using indirect immunofluorescence staining. we identified a striking difference in the content within axons of two neuropeptides, substance P (SP) and calcitonin, gene-related peptide (CGRP), between the contralateral nerve and the neuroma. Unlike the contralateral nerve, where immunofluorescence was sparse, a significant number of disorganized axon profiles that stained brightly positive for CGRP or SP were identified in the neuroma. In contrast, staining for tyrosine hydroxylase, a label of sympathetic axons, was largely absent except around one large arteriole. The neuroma specimen also contained large numbers of serotonin-containing mast cells, only noted occasionally in the contralateral nerve. The peptide staining and mast cell accumulation in the human neuroma closely resembled changes we have previously observed in an animal neuroma model. Local neuropeptides may play a role in the injury response of peripheral nerve, and may be related to mechanosensitivity.