Figure 4: Diagram showing hypothetical mechanisms underlying storage and voiding dysfunction induced by increasing expression of neurotrophic factors following SCI. Injury to the spinal cord causes DSD, leading to functional urethral obstruction, reduced voiding efficiency, urinary retention and bladder hypertrophy, resulting in increased levels of NGF in the bladder. NGF is taken up by afferent nerves and transported to the DRG cells. The levels of NGF also increase in the spinal cord after SCI. TrkA, which responds to NGF, is abundant in bladder afferents, especially C-fiber neurons. Hyperexcitability of bladder C-fiber afferent pathways causes or enhances neurogenic DO. BDNF is also increased in the bladder and the spinal cord after SCI. TrkB, which responds to BDNF, is expressed on larger-sized bladder afferent neurons, presumably Aδ-fiber, that express mechanosensitive receptors, ASIC and Piezo 2. Hyperexcitability of bladder Aδ-fiber afferent pathways causes or enhances DSD. Systemic application of BDNF antibodies reduces BDNF levels in the spinal cord and improves DSD. SCI: Spinal cord injury, DSD: Detrusor-sphincter dyssynergia, NGF: Nerve growth factor, DRG: Dorsal root ganglion, DO: Detrusor overactivity, BDNF: Brain derived neurotrophic factor, TrkB: Tropomyosin receptor kinase B