Neuropeptide- and tyrosine hydroxylase-immunoreactive nerve fibers in painful Morton's neuromas

We examined the expression of three neuropeptides that have been implicated in nociceptive transmission, and the sympathetic nerve fiber marker tyrosine hydroxylase, in 11 painful human Morton's neuromas, using immunohistochemistry. Antibodies against the neural markers RT97 and PGP 9.5 were used to map the general nerve fiber organization of the neuromas. Four specimens of normal human peripheral nerves were used as controls. Substance P, calcitonin gene-related peptide, and neuropeptide Y immunoreactivities were more pronounced in neuroma tissue than in control nerves. Neuropeptide immunofluorescence was seen both in larger nerve fiber trunks and in masses of disorganized axon profiles dispersed in loose connective tissue. Tyrosine hydroxylase immunoreactivity was present at varying levels of expression in neuroma nerve fiber trunks, in connective tissue nerve fiber bundles, and around some blood vessels. Our findings suggest that neuropeptides are involved in the response to injury in Morton's neuromas and that they could play a role in initiation or modulation of pain. In addition, pain from Morton's neuromas could be influenced by sympathetic nerve fibers.