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Journal of Neuroscience, Vol 15, 7633-7643, Copyright © 1995 by Society for Neuroscience
Substance P induced by peripheral nerve injury in primary afferent sensory neurons and its effect on dorsal column nucleus neurons
K Noguchi, Y Kawai, T Fukuoka, E Senba and K Miki
Department of Anatomy and Neuroscience, Hyogo College of Medicine, Japan.
Using in situ hybridization and the retrograde tracer, Fluorogold, we
examined the expression of preprotachykinin (PPT) mRNA in the rat dorsal
root ganglion neurons projecting to the gracile nucleus. Seven days after
unilateral sciatic nerve transection, some medium- to large- sized neurons
in the rat dorsal root ganglia projecting to the gracile nucleus express
PPT mRNA, whereas very few gracile nucleus-projecting neurons on the
contralateral side express PPT mRNA. Immunohistochemistry revealed an
increase in substance P (SP) immunoreactivity in the gracile nucleus and
large myelinated fibers in the dorsal root 2 weeks after unilateral sciatic
nerve transection. The results suggest that medium to large DRG cells that
project to the gracile nucleus express PPT mRNA de novo in response to
peripheral nerve injury, and increased SP is transported to the gracile
nucleus through large myelinated fibers. To determine whether the increased
SP might affect the excitability of the gracile nucleus neurons
postsynaptically, Fos expression after electrical stimulation of the
injured sciatic nerve was examined. Multiple injections of the NK-1
receptor antagonist, CP-96,345, suppressed stimulus-induced Fos expression
in gracile nucleus neurons including thalamic relay neurons. The inactive
enantiomer, CP-96,344, had no effect on stimulus-induced Fos expression.
These data indicate that the de novo synthesized SP in the lesioned primary
afferent neurons may be involved in an augmentation of excitability in the
dorsal column-medial lemniscus sensory pathway. This hyperexcitability may
play a role in the pathogenesis of abnormal neuropathic sensations
following peripheral nerve injury.
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