Structural and functional denervation of human detrusor after spinal cord injury

The bladder receives an extensive nerve supply that is predominantly cholin ergic, but several putative transmitters are present, some of which are col ocalized. Previous studies have shown increased levels of sensory nerves, r educed inhibitory transmitters, and structural and functional changes in th e excitatory input in unstable bladder conditions. The present study compar ed the end-organ nerve supply to the bladder in spinal cord injury (SCI) wi th uninjured controls. Acetylcholinesterase histochemistry and double-label immunofluorescence were used to investigate neurotransmitter content, with confocal laser scanning microscopy to assess colocalization. Organ bath st udies provided functional correlates for the structural changes in the exci tatory innervation. Control samples had dense innervation of the detrusor c ontaining a diverse range of transmitters. Hyperreflexic SCI samples showed patchy denervation, and areflexic SCI samples were diffusely denervated. V asoactive intestinal polypeptide-, neuropeptide Y-, neuronal nitric oxide s ynthase-, and galanin-immunoreactive nerve fibers were reduced from frequen t or moderately frequent to infrequent or very infrequent in SCI. Calcitoni n gene-related peptide-immunoreactive fibers were infrequent in controls an d SCI samples. Patterns of colocalization were unchanged, but significantly fewer fibers expressed more than one transmitter. The subepithelial plexus was markedly reduced and several of the smaller coarse nerve trunks showed no immunoreactivity to the transmitters assessed. There was no reduction i n sensitivity to electrical field stimulation of intrinsic nerves in SCI, b ut the maximum force generated by each milligram of bladder tissue and the peak force as a proportion of the maximum carbachol contraction were signif icantly reduced and the responses were protracted. There was no significant functional atropine-resistant neuromuscular transmission in controls or SC I. The reported findings have clinical implications in the management of ch ronic SCI and development of new treatments.