Affiliations: Department of Anatomy and Cell Biology III, University
of Heidelberg, Germany
Note: [] Correspondence to: Prof. Dr. Siegfried Mense, Institut für
Anatomie und Zellbiologie III, Universität Heidelberg, Im Neuenheimer Feld
307, D-69120 Heidelberg, Germany; Tel. +49-6221-548305; Fax.
+49-6221-546071
Abstract: The urine storage ability of the urinary bladder is markedly
impaired following inflammation of the urinary bladder and spinal cord injury
because of a hyperexcitability of micturition reflexes. Using two rat models of
inflammation-induced bladder overactivity and detrusor hyper-reflexia following
spinal cord injury we investigated changes in the neuronal pathways to the
urinary bladder which may underlie the development of this instability. Our
results suggest that among the factors involved in inflammation-induced bladder
instability are significant changes in the expression of the neuropeptides
substance P, calcitonin gene-related peptide and galanin at the primary
afferent level, as well as of the enzyme neuronal nitric oxide synthase (nNOS)
at the afferent and postganglionic efferent level. In the lumbar and sacral
spinal cord nNOS-immunoreactivity was depleted from dorsal horn neurones in
both cystitis and spinal cord injured rats and from preganglionic
parasympathetic neurones after spinal cord injury. Distension of the bladder in
chronically spinalized rats elicited c-Fos expression in a significantly
greater number of neurones throughout the lumbar and sacral segments than in
rats with an intact neuraxis. Thus, under pathological conditions rather
complicated changes in the synthesis of neuropeptides and nNOS occur at the
primary afferent, spinal cord and postganglionic efferent level that together
control the activity of the urinary bladder. Further mechanisms like unmasking
of silent synapses and axonal sprouting in the spinal cord might further
contribute to an increase in activity in micturition reflex pathways. Local
cooling of the dorsal spinal cord at the level L6/S1 with temperatures between
14 and 20 °C proved a simple technique to control the unstable bladder and
restore continence in both inflammation-induced detrusor overactivity and
detrusor hyperreflexia following spinal cord injury. The effects of cooling are
probably the result of a blockade of synaptic transmission within the dorsal
cord which eliminates neuronal overactivity. Thus, local spinal cord cooling
could offer a new method to treat bladder instability and reflex
incontinence.
