## 3 Discussion  
Management of CPPS needs a holistic approach with active patient involvement. Indeed, most of the time single interventions do not work in isolation and should be considered together in order to give the patients a personalized care. Treatments may include psychological therapy, due to the presence of associated negative cognitive symptoms such as anxiety, and behavioral consequences, physical therapy, pharmaco-therapy and sometimes surgery. CPPS should be addressed in a multispecialty and multidisciplinary environment with the collaboration of different experts, such as urologists, gynecologists, pain therapists and physiotherapists, to take in consideration all patients symptoms. History, followed by physical examination, are the first steps to evaluate patients with CPP and collect all functional and pain-related symptoms aiming to identify the CPPS subtype and select the best treatment options [1]. Botulinum is a bacterial neurotoxin acting as a presynaptic neuromuscular blocking agent and inhibiting the release of acetylcholine from nerve fibers endings. This effect determines a transitory skeletal muscle relaxation and produces an analgesic effect by reducing muscle hyperactivity [7]. nociceptive effects of botulinum toxin A are also showed on sensory neurons through the preventing of the neurotransmitter release, from sensory peripheral nerve fibers, involved in pain genesis [28]. Botulinum toxin is a recognized treatment option for autonomic disorders, spasticity and hyperkinetic movement disorders, for treating wrinkles in the cosmesis [29], for upper limb spasticity, hemifacial spasm, blepharospasm and hyperidrosis [30]. It has been also used to treat various pain disease, such as cervical dystonia and chronic migraine, which remains the only approved pain indication, even though several clinical trials have investigated the efficacy and safety of botulinum toxin in other different pain condition [31]. BTX-A for the treatment of CPPS is still in off-label use. In the European Association of Urology (EAU) guidelines, BTX-A is reported as a treatment option only for CP/PPS, pelvic floor pain and chronic primary anal pain syndrome [1]. Several studies have addressed the role of BTX-A in these diseases, even though with no definitive conclusion and subsequentially no absolute indication in favor of its efficacy can be assumed [1]. In this systematic review, we investigated the efficacy of BTX-A injection in CPPS management. We have selected only prospective studies and then have grouped them among CPPS subtypes to facilitate data interpretation, analyses, and comparison. However, the methodologically heterogeneity between the included studies regarding the study design, the definition of CPPS subtype, intervention and control groups, number and sexes of patients, type and dose of drug administered, number and location of injections delivered, outcome measured and time of follow up make it difficult to interpret data uniquely and to draw definitive conclusions. Figure 5: Pooled meta-analysis results and Forest plot showing the differences in pain scores between baseline and last follow up assessment for 6 included cohorts of four considered studies that evaluated the efficacy of BTX-A injection for GPP. The studies included in our work used different criteria to define the specific CPPS sub-category. Among IC/BPS five studies used the National Institutes of Diabetes and Digestive and Kidney Disease (NIDDK) criteria, two cystoscopy findings, and one study did not provide any definition. All three studies assessing the role of BTX-A in CP/PPS enrolled men who met the National Institutes of Health criteria for type IIIA /IIIB chronic prostatitis. Patients' recruitment in the studies investigated the efficacy of BTX-A in GPP or MPP was established according to both clinical findings and diagnostic evaluation. BTX-A formulation is an important issue to state when making a comparison due to different types of BTX-A showing different potency.