(A) Diseases and trauma of the nervous system This is one of the important causes of voiding dysfunction, which can manifest as OAB symptoms and hyperactivity of the detrusor muscle. For example, multiple sclerosis, stroke, diabetes mellitus, Alzheimer’s disease, spinal stenosis, spinal cord injury, and spinal cord dysplasia are common causes. Urodynamic studies allow an evaluation of bladder forced urinary muscle tone and stability and external sphincter coordination due to these diseases. Cystometry reveals increased bladder tone and hyperreflexia, with similarities to LUTS in patients with BOO. It is now clear that the superior pontocerebrum can exert an inhibitory effect on the pontocerebral voiding center. Damage to the superior pontine region during stroke or Alzheimer’s disease can weaken this inhibitory effect. In contrast, damage to the suprasacral spinal nerve blocks the autonomic action and the regulation of the suprasacral nerve, causing reflex urination. These neurological abnormalities are accompanied by a sensory deficit and a variation in the synergistic action of the external sphincter during voiding events. In neuropharmacological experiments it was found that the afferent activity of the nerve was altered from myelinated A afferent fibers to unmyelinated C afferent fibers which can be unresponsive to bladder distension and variability in the electrical excitability of C afferent fibers of the bladder.C afferent fibers have capsaicin sensitive properties and can be therapeutic with capsaicin for OAB due to spinal cord injury and multiple sclerosis. The good therapeutic effect of capsaicin suggests that OAB can be mediated by capsaicin-sensitive C afferent fibers. (B) Effects of bladder outlet obstruction (BOO), BOO can be caused by BPE, bladder neck dysfunction, posterior urethral valve, external sphincter synergistic dysfunction, spinal cord dysplasia, Hinman syndrome and medically induced obstruction. BOO due to prostate disease is much more prevalent than BOO due to neurological trauma and disease, and instability of contraction of the detrusor muscle can be detected on cystometry. Symptoms of prostate-induced BOO are usually described by LUTS, which are associated with an unstable bladder, although LUTS are described symptomatically. In many patients, unstable bladder contractions can improve after prostatectomy and LUTS symptoms improve, suggesting an important association of bladder instability with LUTS. Urodynamic studies in patients with LUTS have found a 25-75% incidence of instability of the detrusor muscle. Histological, pharmacological, and physiological studies using animal-made BOO models have confirmed that BOO can cause contractile instability and tissue structural abnormalities in the bladder’s forced urinary muscles, and that these changes may cause OAB symptoms and changes in bladder dynamics. Because LUTS is mostly subjective and the use of animal experiments only allows the observation of histophysiological changes in muscle histology before and after treatment, the current findings have not revealed a direct causal relationship between LUTS and BOO. Studies on the basis of bladder dysfunction due to BOO have focused on a series of changes in the bladder forcing muscles, denervation and voiding reflexes. Increased bladder weight after the occurrence of BOO, histological findings of hypertrophy and hyperplasia of myocytes, increased collagen deposits and absence of parasympathetic nerve endings. Pharmacological experimental studies revealed a denervated allergic response of the muscle strips taken from the obstructed bladder to the stimulation of cholinergic drugs, while the stimulatory response of the nerves was significantly diminished. Arterial blood flow and tissue oxygen-water averages were reduced during contraction of the detrusor muscle, and post-denervation ischemic damage occurred. Studies of muscle contraction showed a decrease in muscle contractility and a decrease in the energy required to maintain muscle contraction. Electrophysiological studies revealed poor current stability and abnormal current spreading patterns in hyperplastic myocytes compared to normal cells. These results confirm that in the contraction of the hyperplastic bladder, the threshold for receiving stimuli is decreased, the contraction force becomes weaker, and the duration of contraction is shortened. During BOO, both bladder afferent and efferent nerves are affected. In the murine model of BOO, afferent and efferent nerves of the bladder proliferate, exhibiting increased voiding reflex activity and a pattern of bladder overactivity on the pressure map. Nerve growth factor was also increased in the obstructive bladder, which coincided with afferent nerve proliferation. (iii) Abnormalities in forced urinary muscle function in older patients: LUTS and OAB are often seen in both male and female elderly patients who have hyperreflexia and impaired contractility of the forced urinary muscles with a prevalence of up to 60%. Bladder manometry in these patients reveals an overactive bladder with incomplete emptying, which can be non-obstructive. Histologic changes in the elderly bladder have increased cell-to-cell protrusion connection patterns, and in patients with impaired contractility, degeneration of the forceps cells and nerve axons, capsaicin-sensitive unmyelinated C afferent fibers responsible for afferent pain, bladder filling and urinary urgency sensation, and increased nerve afferent activity can cause LUTS and OAB as seen clinically.(iv) Chronic prostatitis or chronic pelvic pain syndrome ( CP/CPPS) voiding phase symptoms: often caused by bladder outlet obstruction (e.g., BPH), can likewise occur in conditions such as prostate cancer, urethral stricture, and chronic prostatitis. Prostatitis can cause both voiding and storing symptoms. Unlike LUTS caused by BPH, symptoms caused by CP or CPPS are mainly post-ejaculatory pain, pain in the perineum and suprapubic area, and reduce the quality of life. Some patients may have BPH, but the cause of most cases remains unclear. The mechanism of action of alpha1 adrenoceptor blockers in relieving symptoms is not fully understood and is related to the reduction of pressure in the urethra and the reduction of urinary reflux in the prostate.