The myogenic factor was best explained by Brading7 who stated that alterations in the properties of the detrusor myocytes are a necessary prerequisite for the production of an involuntary detrusor contraction, which in turn causes an unstable increase of Selleck Obeticholic Acid intravesical

pressure. It has been recently reported that events leading to enhanced intravesical pressure during voiding may result in periodic ischemia of the bladder resulting in damage to some intrinsic neurons in the bladder wall and secondary changes in smooth muscle properties over time.8,9 These changes may then increase excitability and electrical coupling between cells. A local contraction occurring in any part of the detrusor will then spread Caspase activity throughout the bladder wall, resulting in coordinated myogenic contraction of the entire bladder.7,10,11 In addition, partial denervation of the detrusor may cause supersensitivity

of detrusor to neurotransmitters, which consequently augments the response to stimulation.12 Sui et al. recently demonstrated that spontaneous, autonomous cellular activity—Ca2+ and membrane potential oscillations, originates from human detrusor smooth that is mediated by extracellular Ca2+ influx and intracellular release.13 Such cellular activity underlies spontaneous muscle contraction and defective Ca2+ activation contributes to upregulated contractile activity in overactive bladders. The neurogenic factor suggests that damage to central inhibitory pathways in the brain and spinal cord or sensitization of peripheral afferent terminals in the bladder can unmask primitive voiding reflexes that trigger detrusor overactivity. This can result from damage to the brain, which can induce

detrusor overactivity by suppressing suprapontine inhibition; damage to axonal pathways in the spinal cord leads to the emergence of primitive spinal bladder reflexes most triggered by C-fiber bladder afferent neurons.14 Neurogenic causes may be seen in patients who have multiple sclerosis, cerebrovascular events and Parkinson’s disease. Kessler et al. reported that thalamic deep brain stimulation resulted in an earlier desire to void and decreased bladder capacity,15 suggesting a regulatory role of the thalamus in lower urinary tract function. Recent brain imaging studies have also demonstrated that bladder control depends on an extensive network of brain regions, and dysfunction in various parts may contribute to urge incontinence.16 Abnormality in nonadrenergic noncholinergic (NANC) neurotransmission may also cause OAB. O’Reilly et al. were unable to detect a purinergic component of nerve-mediated contractions in control (normal) human bladder preparations but found an approximately 50% purinergic-mediated component in OAB specimens.17 They concluded that this abnormal purinergic transmission in the bladder might explain symptoms in OAB patients.