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Journal of Neuroscience, Vol 12, 4878-4889, Copyright © 1992 by Society for Neuroscience
Increased c-fos expression in spinal neurons after irritation of the lower urinary tract in the rat
LA Birder and WC de Groat
University of Pittsburgh School of Medicine, Department of Pharmacology, Pennsylvania 15261.
This study utilized neuronal c-fos expression to examine the spinal
pathways involved in processing nociceptive and non-nociceptive afferent
input from the lower urinary tract (LUT) of the urethane- anesthetized rat.
C-fos protein was detected immunocytochemically in only a small number of
cells (< 2 cells/L6 section) in control animals. However, chemical
irritation with 1% acetic acid or mechanical stimulation of the LUT
markedly increased the number of c-fos-positive neurons (56-180 cells/L6
section) in four regions of the caudal lumbosacral (L6-S1) spinal cord:
medial dorsal horn (MDH), lateral dorsal horn, dorsal commissure (DCM), and
sacral parasympathetic nucleus (SPN). Only small numbers of c-fos-positive
cells were detected in rostral lumbar segments, a region that is thought to
receive nociceptive input from the LUT via afferent pathways in sympathetic
nerves. The distribution of c-fos-positive cells in the L6 spinal cord
varied according to the stimulus (i.e., urethral catheter, bladder
distension, or chemical irritation). Distension of the urinary bladder
increased the number of c-fos-positive cells mainly in DCM and SPN regions
of the cord. In contrast, irritation of the LUT increased c-fos expression
largely in DCM and MDH areas. Spinal cord transection (T8 level) did not
alter the c-fos expression induced by a catheter or chemical irritation,
indicating that gene expression was mediated by spinal pathways.
Denervation experiments showed that c-fos expression was induced by
activation of afferent pathways in the pelvic and pudendal nerves. These
results suggest that neurons in several regions of the spinal cord are
involved in processing afferent input from different parts of the LUT.
Neurons in the DCM appear to have an important role since they respond to
both nociceptive and non- nociceptive inputs and to visceral (pelvic nerve)
and somatic (pudendal nerve) afferent pathways. Thus, these neurons may be
involved in the mechanisms of visceral-somatic referred pain.
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