Spinal interneurons and micturition reflexes: focus on “Characterization of a spinal, urine storage reflex, inhibitory center and its regulation by 5-HT_1A receptors in female cats”

Abstract

GENERATIONS OF EFFORT HAVE been devoted to understanding how the human body stores and periodically releases urine. Micturition is regulated by neural circuits in the brain and spinal cord that coordinate the activity of the smooth and striated muscles of the lower urinary tract (LUT) (7,9,10,12). These circuits act as on/off switches to shift the urinary tract between two modes of operation: storage and elimination. Storage and periodic elimination of urine requires a complex neural control system that coordinates activities of a variety of effector organs including bladder smooth muscle and smooth and striated muscle of the urethral sphincters and multiple levels of nervous system integration (15,16). Three neural pathways regulate the LUT: 1) sacral parasympathetic (pelvic) nerves provide excitatory input to the bladder; 2) thoracolumbar sympathetic nerves provide inhibitory input to the bladder and excitatory input to the bladder neck and urethra; and 3) sacral somatic (pudendal) nerves innervate the striated muscles of the sphincters and pelvic floor (15,16). Each of these sets of nerves contains afferent (sensory), as well as efferent (motor), axons. Lower urinary tract reflex mechanisms organized at the level of the lumbosacral spinal cord are modulated predominantly by supraspinal control (7,9,12,16).Dysfunction of neural control of LUT functions presents a major problem in clinical management of patients suffering from a large number of neurological injuries (e.g., upper motor neuron disease after spinal cord injury, stroke) or disorders (e.g., multiple sclerosis, Parkinson's disease) (1, 2). Deficits on the afferent and efferent limbs of the micturition reflex are associated with a wide range of clinical urinary tract problems. Deficits on the afferent side will affect reflex function and sensation and may contribute to bladder pain syndrome/interstitial cystitis along with urothelial dysfunction and mast cell involvement (18). Deficits on the efferent side of the reflex can affect the detrusor smooth muscle and urethral outlet. Stress urinary incontinence, a prevalent condition in women, is characterized by a reduction in outlet resistance during urine storage due to weakness in the urethral sphincter/rhabdosphincter mechanism due to target tissue weakness and/or peripheral nerve dysfunction (4). Information related to normal organization of the micturition reflex and its alteration have tremendous potential to increase our understanding of bladder disorders and develop new therapeutic approaches. Micturition ReflexVoiding reflex. Elimination of urine involves coordinated contraction of detrusor and relaxation and dilation of the urethral outlet. This involves inhibition of sympathetic output to the bladder and urethral outlet and activation of the parasympathetic pathway. Relaxation of urethral smooth muscle is achieved by reduction of adrenergic and cholinergic excitatory inputs and release of nitric oxide to elicit smooth muscle relaxation (12)