**7. Potential Impact of BoNT-A Injection on: The UPOINT Phenotype System**

Clinically, it is challenging to achieve satisfactory outcomes for CP/CPPS treatment. In most cases, monotherapy has failed to successfully treat CP/CPPS, largely because of the heterogeneous nature due to multiple factors involved in the pathogenesis of CP/CPPS, such as pelvic floor muscle dysfunction, chemical irritants, as well as neurological and immunological factors. With these unsatisfactory treatment responses, combination therapies and individual consideration provide another way to improve the efficacy of treating patients with CP/CPPS. In 2009, Shoskes et al. developed the UPOINT system to classify patients with CP/CPPS to help clinicians understand the etiology and more importantly, to guide the treatment [46]. The UPOINT phenotype system includes six domains to evaluate and manage CP/CPPS: **U**rinary symptoms, **P**sychosocial dysfunction, **O**rgan-specific findings, **I**nfection, **N**eurologic/systemic complaints, and **T**enderness. Each domain has been related to specific mechanisms and treatments [7]. Patients with "urinary" complaints (storage, voiding symptoms or much post-void residual urine) can be treated with α-blocker, diet modification, and/or antimuscarinics. Intraprostatic BoNT-A can also relieve urinary symptoms [17,19,20]. "Psychosocial" patients with depression or catastrophizing evidence can be managed with counseling, cognitive behavioral therapy, antidepressants, or stress reduction. In the "organ-specific" group presenting with tenderness on prostate, increased leukocytes in prostatic fluid, blood in semen, or prostatic calcifications, some anti-inflammatory agents such as quercetin can be considered. BoNT-A has been shown to have effects on the inhibition of COX-2 expression in a preclinical prostatitis models [24,25], from which beneficial effects might reduce prostate inflammation in human CP/CPPS. Patients with "infection" (exclusion of NIH category I or II prostatitis) can be treated with antibiotics. "Neurologic/systemic" patients usually present with pain beyond abdomen and pelvis or other complaints, such as irritable bowel syndrome, fibromyalgia or chronic fatigue syndrome. In these kinds of patients, neuroleptic medications can be used to relieve symptoms. In the domain of "tenderness", trigger points may be noted in the abdomen or pelvic floor, and treatments may include muscle relaxants use, pelvic floor physical therapy (PFPT), low-intensity shock wave, or PFPT in combination with adjuvant trigger point injection [47,48]. BoNT-A injection targeting at the pelvic muscle or trigger point might ameliorate the symptom of tenderness. Using the UPOINT system in classifying patients with CP/CPPS can facilitate hypothesis testing for possible etiologies and treatment. Shoskes et al. found that the number of positive domains was associated with severity and duration of complaints [46]. Their group also conducted a prospective study using UPOINT approach in treating 100 patients with CPPS. Eighty-four percent of patients had at least a 6-point improvement in NIH-CPSI at a median follow-up of 50 weeks [49]. Similarly, another prospective study of 140 Chinese men with CP/CPPS based on the UPOINT approach also showed a 75% response rate with a follow-up of 6 months [50]. Taken together, increasing evidence has shown that the UPOINT phenotype system is feasible and effective to clinical physicians in treating CP/CPPS. The BoNT-A prostate and pelvic muscle injection might have direct or indirect effects on the domains of **U**rinary symptoms, **P**sychosocial dysfunction, **O**rgan-specific findings, **N**eurologic/systemic complaints, and **T**enderness.
