Neuroscience
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Peripheral neuropathy can be associated with a variety of symptoms, including spontaneous unpleasant sensations and pain, as well as increased sensitivity to sensory stimuli. A peripheral neuropathy model involving an L5 spinal nerve lesion in male rats has been used to gain insight into the mechanisms that underlie symptoms that develop after nerve injury. This model was used to study the involvement of sensory fibres, the sympathetic postganglionic neuron and the role of nerve growth factor in the induction and maintenance of altered sensory function in the nerve territory of the intact L4 spinal nerve. ⋯ Two pathophysiological mechanisms leading to central changes may be necessary to produce altered sensations in this model: (i) ongoing activity in C-fibres, independent of sympathetic postganglionic neuron activity and (ii) activity in sensory fibres modulated by a sensory-sympathetic interaction in the injured spinal nerve or dorsal root ganglion. The sympathetic postganglionic neuron contribution is independent of preganglionic sympathetic outflow from the central nervous system, suggesting a novel mechanism by which sympathetic efferent terminals can regulate sensory fibre activity. A contribution of a loss of neurotrophic factors to the sympathetic postganglionic neuron following nerve lesion is also suggested to contribute to the symptoms induced by the spinal nerve lesion.
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In this study co-localization of galanin- with calcitonin gene-related peptide (CGRP)-like immunoreactivity was examined in dorsal root ganglion neurons 14 days after sciatic nerve cut using a laser scanning confocal microscope. CGRP- and galanin-like immunoreactivities were also analysed in the dorsal horn of the spinal cord of these animals with immunofluorescence microscopy. The ultrastructural changes in galanin-immunoreactive, presumably primary afferent terminals in the superficial dorsal horn, were studied as well as the relationship between galanin-, substance P- and CGRP-like immunoreactivities in primary afferent terminals. ⋯ They did not form glomeruli and contained few large dense-core vesicles. Post-embedding immunocytochemistry combined with quantitative analysis revealed that significant changes occurred in a proportion of terminals also with regard to peptide content in large dense-core vesicles after axotomy. Thus, the percentage of galanin-positive large dense-core vesicles increased in several cases and that of substance P- and CGRP-immunoreactive ones decreased.(ABSTRACT TRUNCATED AT 400 WORDS)
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The effect of RPR 100893, a selective and specific neurokinin-1 antagonist, or its enantiomer RPR 103253 was examined on c-fos antigen expression in brain stem and upper cervical cord 2 h after intracisternal capsaicin injection (30.5 micrograms/ml) in pentobarbital-anesthetized Hartley guinea-pigs. Positive cells were counted at three levels corresponding to obex, -2.25 mm and -6.75 mm in 18 sections (50 microns). Immunoreactivity was strongly expressed within laminae I and IIo of trigeminal nucleus caudalis, area postrema and the leptomeninges. ⋯ These results indicate that (i) the instillation of capsaicin into the subarachnoid space is an effective stimulus for the induction of c-fos antigen within trigeminal nucleus caudalis, presumably through activation of trigeminovascular afferents, and (ii) the neurokinin-1 antagonist RPR 100893 reduces the number of positive cells selectively within this nucleus. The findings are significant because drugs which alleviate vascular headaches decrease the number of c-fos-positive cells within trigeminal nucleus caudalis following noxious meningeal stimulation. Hence, strategies aimed at blocking the neurokinin-1 receptor may be useful for treating migraine and cluster headache.