neuropeptide-y and Neuroma

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.

Topics: Adult; Aged; Antibodies; Calcitonin Gene-Related Peptide; Cell Communication; Female; Foot Diseases; Humans; Male; Middle Aged; Nerve Fibers; Neuroma; Neurons, Afferent; Neuropeptide Y; Neuropeptides; Pain; Substance P; Sympathetic Nervous System; Thiolester Hydrolases; Tyrosine 3-Monooxygenase; Ubiquitin Thiolesterase

Injury to branches of the trigeminal nerve can sometimes result in persistent dysaesthesia. In an attempt to understand the aetiology of this condition we are currently investigating changes which occur at the injury site. In the present study we have examined the expression of seven neuropeptides, all of which have been implicated in nociceptive transmission, or have previously been shown to have altered expression following nerve injury. In 20 adult ferrets the inferior alveolar nerve was sectioned and ligated, and recovery permitted for 3 days, 8 days, 3 weeks, 6 weeks or 12 weeks. Longitudinal sections of the neuromas were processed using immunohistochemical techniques to quantify the expression of substance P, calcitonin gene-related peptide, vasoactive intestinal polypeptide, galanin, somatostatin, enkephalin and neuropeptide Y. After 3 days, all of the neuropeptides were expressed at the injury site. In the neuromas examined after longer recovery periods these levels of expression had declined and were similar to those found in the contralateral controls. This initial high level, followed by a decline, parallels the incidence of ectopic neural activity recorded electrophysiologically in the same model. It is, therefore, possible that the accumulation of neuropeptides at the injury site may play a role in the initiation or modulation of ectopic neural activity.

Topics: Animals; Calcitonin Gene-Related Peptide; Constriction; Cranial Nerve Neoplasms; Enkephalins; Female; Ferrets; Galanin; Immunohistochemistry; Male; Mandibular Nerve; Neuroma; Neuropeptide Y; Neuropeptides; Somatostatin; Substance P; Vasoactive Intestinal Peptide

Neuropeptide Y (NPY)-like immunoreactivity was examined by fluorescence immunohistochemistry in rat sciatic neuromas, L5 dorsal root ganglias (DRGs) and L5 dorsal roots 1-3 weeks after chronic nerve injury. Anterograde tracing demonstrated that a large number of NPY-positive neuroma fibers were sensory. These fibers were mostly large diameter axons, in line with the finding that a majority of NPY-immunoreactive neurons in the DRG were medium- to large-sized neurons which showed immunoreactivity to the neurofilament antibody RT 97. In dorsal roots NPY immunoreactivity was strong after sciatic neuroma formation. Dorsal rhizotomy and ligation, on the other hand, did not induce NPY immunoreactivity at any of the sites examined.

Topics: Animals; Fluorescent Antibody Technique; Nerve Fibers; Neuroma; Neuropeptide Y; Peripheral Nervous System Neoplasms; Rats; Rats, Inbred Strains; Sciatic Nerve; Sensory Receptor Cells

Substance P (SP)-, calcitonin gene-related peptide (CGRP)- and neuropeptide Y (NPY)-immunoreactive nerve fibers were examined in experimental sciatic nerve-end neuromas in the rat with immunohistochemical techniques. At 1-3 days after nerve ligation and section of the sciatic nerve there was an accumulation of SP-like immunoreactivity (SP-LI). Six days after the lesion there was, however, a marked reduction and the neuromas remained virtually depleted from SP-LI at survival times between 8 days and 3 months. CGRP-LI was strong at 1-5 days post-operatively. By 8 days, CGRP-LI was reduced, but a large number of axons were still immunoreactive, and remained immunolabelled up to 3 months. CGRP-LI nerve fibers formed endbulbs, and appeared to grow in both anterograde and retrograde directions. Fine fibers sprouts were first observed at 8 days, but preterminal branching in neuromas aged less than a month was uncommon. At early stages (1-3 days) after ligation, there was a marked accumulation of NPY-LI proximal to the nerve constriction. NPY-LI was reduced from 5 days and on, but many fibers remained NPY-positive and their growth pattern through proximal and distal neuroma segments could be determined. The present results thus may indicate a differential effect of nerve injury on neuropeptide expression: immunohistochemically detectable SP-LI rapidly disappears from sciatic nerve fibers trapped in nerve-end neuromas, but CGRP-LI and NPY-LI remain and are useful as neuroanatomical markers for two subclasses of sprouting axons. Furthermore, the findings suggest that both CGRP and NPY, but not SP, could be involved in ectopic electrical activity in experimental neuromas.

Topics: Animals; Biomarkers, Tumor; Calcitonin Gene-Related Peptide; Male; Nerve Fibers; Neuroma; Neuropeptide Y; Neuropeptides; Peripheral Nervous System Neoplasms; Rats; Rats, Inbred Strains; Sciatic Nerve; Substance P

An indirect immunohistochemical technique was used to identify neuropeptide Y (NPY)-immunoreactive nerve fibers in the lumbosacral pia mater of normal cats and in kittens previously subjected to sciatic nerve resection. It was shown that NPY-positive fibers both associated with blood vessels and lacking vascular relation occur in the pia mater of normal cats. After nerve lesion some fibers which were not associated with blood vessels ramified extensively in the pia mater and formed thin beaded branches which ended blindly.

Topics: Amputation Stumps; Animals; Blood Vessels; Cats; Fluorescent Antibody Technique; Nerve Fibers; Nerve Tissue Proteins; Neuroma; Neuropeptide Y; Pia Mater; Sciatic Nerve