I. Definition Chronic pelvic pain (CPP) refers to a multifactorial disorder in men or women with benign pelvic pain lasting or recurring for more than 6 months or periodic episodes for more than 3 months, pain associated with negative cognition, behavior, sexual activity and emotions, accompanied by lower urinary tract symptoms and bowel, pelvic floor, gynecological or sexual dysfunction. CPP without significant local pelvic organ or tissue infection or other pathological changes is called chronic pelvic pain syndrome (CPPS). pain sensations in CPPS that can be localized to a particular organ are named after that organ pain syndrome, e.g., prostate pain syndrome. pain symptoms in CPPS that cannot be localized to If the pain sensation of CPPS can be localized to a particular organ or appears in multiple organs, it is named as CPPS. It is often difficult to clinically differentiate between these two conditions because of the lack of validated specific indicators.CPPS can also be divided into several subtypes, such as bladder pain syndrome in which the bladder is mainly characterized by inflammation of Hunner’s ulcer, called the inflammatory type.CPP pelvic organs and tissues with obvious pathological features (e.g., infection, tumor) are associated with specific diseases Pelvic pain, named after related diseases, such as prostate cancer. II. pathogenesis of CPPS There are multiple etiologies and multiple pathogenesis of CPPS, which is more likely to be a cascade amplification effect under the initial inducing factors.CPPS is the result of the interaction of mental factors, immune dysfunction, neurological dysfunction and endocrine dysfunction. 1. Peripheral visceral pain Early in CPPS there may be inflammation or infection, and altered peripheral tissues lead to increased receptor sensitivity, amplifying the incoming injurious stimulus signal. Increased release of chemical transmitters causes changes in many transmitter receptors, decreased thresholds or increased sensitivity to external stimuli, and persistent perception of pain by peripheral organs in the absence of pathology. Peripheral stimuli (e.g. sensation) may be the trigger for pain, but the continuation of pain in CPPS is no longer dependent on the above trigger. it is not beneficial to repeatedly search for causative factors after CPPS has ruled out the obvious causative factors. 2. Central sensitization Many pathogenic mechanisms of CPPS are based on the central nervous system and are closely related to sensory, functional, behavioral and psychological changes. Altered protein activity, altered protein transcription levels and structural changes in neural connectivity processes are involved in the central sensitization process. Repeated stimulation of nociceptive afferent fibers increases the intracellular calcium ion concentration, decreases the excitation threshold of second-level neurons, and more signals are transmitted to higher-level centers. Calcium ions enhance phosphorylation of amino acids in response to kinase, altering protein structure, lowering channel opening thresholds, and prolonging channel opening times, amplifying the effects of stimulation in these neurons. Mild somatic (touch) or visceral (urinary bladder storage) stimuli can produce central sensitization. The brain has both a downstream pathway for pain inhibition and a downstream pathway for pain perception, and the periaqueductal gray (PAG) plays a major role in pain regulation at the spinal cord level. Some neurotransmitters such as opioids, 5-hydroxytryptamine and norepinephrine are involved in reducing the conductivity of pain inhibitory pathways. 3. Psychological and neuromodulation Pain is not only associated with complex perceptual damage activation, but also an emotional response. Pain is an unpleasant sensory and emotional experience associated with actual or potential tissue damage. The psychological processes that influence emotions, thoughts and behaviors are a network rather than a specific region. There are interactions between many areas closely associated with mental activity and midbrain conductors that influence the transmission of pain at the level of the spinal cord. Normal sensations in the viscera and injury sensations are transmitted to the spinal cord by the same fine fibers, and mental conditioning can alter the strength of signal encoding and affect pain perception more than dual fiber transmission in the somatic nerves. Various psychological processes can influence pain at higher levels of neuromodulation and can also modulate the response to injurious information. This psychological modulation may reduce injurious stimuli in short periods of time, and if prolonged exposure to that stimulus is enhanced through long time courses, leading to subsequent long-term vulnerability to perceive chronic visceral painful stimuli and enhanced sensitivity to perceived stimuli. Stress is an adaptive response that induces the endocrine system, the vegetative nervous system, and the immune system, among others. Stress plays an important role in the ability to perceive injury and in the neural modulation of pain, affecting one’s emotional, cognitive, and sexual responses. Symptom-related anxiety and amplification of central pain may be significantly correlated. The failure of amplification, amplification, and inhibition has multiple psychogenetic mechanisms and complex relationships between signs, pain experience, distress, and activity constraints. Depression may simply be a consequence of persistent pain without a cause. 4, sexual behavior and chronic pelvic pain Pelvic pain in either men or women can lead to sexual dysfunction for multiple and interacting reasons, possibly related to comorbid depression, antidepressant use, the degree of beauty of the couple, and many other factors. Pain can affect a person’s self-esteem and their ability to derive pleasure from sex and sexual relationships. Pelvic pain can affect sexual response and impede freedom of movement, while male functioning problems can also have an impact on their sexual partners. Pain can reverse sexual arousal, causing penile weakness in men or cessation of synovial fluid production in women. Chronic pain can reduce the frequency of sexual activity and sexual satisfaction, as well as relationship satisfaction. In a study conducted in the United Kingdom, 73% of patients with chronic pain experienced pain-related sexual function problems of varying degrees. Opioid analgesics, 5-hydroxytryptamine inhibitors, and SSRIs can also cause decreased sexual desire and delayed ejaculation. The overall prevalence of sexual dysfunction in 1768 patients with prostate pain syndrome (PPS) in China was 49%, with premature ejaculation and ED being the most common. The prevalence of ED in PPS was 27.4%, 15.2% and 43% in Italy, Turkey and Finland, respectively, with a high prevalence of sexual dysfunction. Patients who suffered sexual, physical or emotional abuse had a higher chance of developing CPPS symptoms. 5, pelvic floor function and chronic pelvic pain The pelvic floor is composed of muscles and fascia, with three functions: support, contraction and diastole. Pelvic pain and pelvic floor muscle dysfunction, especially with pelvic floor muscle overactivity, are interrelated and causally related to each other. Both pelvic floor muscle and pelvic organ dysfunction can be transmitted as primary signals to the spinal cord, which continue to be transmitted upward to the central nervous system of the brain by way of cascade responses. The result is that the muscles contract on their own and remain in a hypertonic state even when they are in diastole. Central nervous system pathology leading to pelvic floor dysfunction may be one of the main mechanisms of chronic pelvic pain. Trigger points exist in the myofascia, which are high stress points on the hypertonic muscle bundle and have the characteristic of being closely associated with pain and the appearance of pain when stretching the muscle. Trigger points exacerbate pain with increased pressure, sustained or repeated contractions. Deformities of the hip or lower extremity, sexual abuse injuries, trauma, abnormal exercise or sexual activity, recurrent infections and surgical procedures can all lead to increased stress on the myofascial trigger point, which is a predisposing factor for pain. The diagnosis of CPPS is a diagnosis of exclusion. CPPS is a common response to different types of damage caused by multiple etiologies, and patients often have other sensory, functional, behavioral and psychological changes in addition to pain. 1. Medical history The duration of pelvic pain, whether it is constant, intermittent or cyclic. The cause of pain, the relationship between pain and emotional changes, and the relationship between pain and postural changes. The location of the pain, whether it is confined to a specific pelvic organ or involves multiple pelvic organs. Quantification and evaluation with relevant quantitative scales if necessary, such as pain rating (which can be assessed by cognitive and affective variables), International Index of Erectile Function (IIEF), intravaginal ejaculation latency (IELT), depression score, and quality of life score (QOL). Understanding anxiety, depression and sexual problems is important for assessing pain and developing a treatment plan. Whether sexual, somatic or emotional abuse has been suffered, and the socio-psychological status at the time of pain presentation. 2. Physical examination Is there any clear localization of pelvic pain, and are there any organic changes at the site of pain, such as size, texture, mass, and pressure pain of the testes, epididymis, and prostate. Check for trigger points of myofascial pain and muscle pain that may span (referred pain). Rectal palpation or vaginal palpation to understand the functional status of pelvic floor muscles. 3.Laboratory examination Including routine urinalysis and urine sediment examination, EPS routine examination, bacteriological examination by four-cup (or two-cup) method, etc. 4.Special tests include cystourethroscopy, external genital ultrasonography, transrectal prostate ultrasonography, and CT and MRI imaging if necessary. Electromyography is an optional adjuvant test for the diagnosis of CPP. The aim of the diagnosis is to exclude specific diseases of pelvic pain, such as infections and tumors. Once the obvious causative factors have been ruled out, there is no need for repeated or excessive effort to further define the causative factors. Treatment of CPPS The pathogenesis of CPPS is complex and varied, and the treatment of CPPS requires a combination of biological means, psychological means, and social factors to achieve a holistic treatment. the treatment of CPPS requires the participation of psychological, sexual medicine, physical therapists, and pain physicians in addition to urologists, gastroenterologists, and gynecologists. Pelvic floor muscle function is closely related to pelvic pain and the arousal and orgasmic phases of the sexual response, and pelvic floor muscle therapy approaches are the first-line treatment option for CPPS. Pelvic floor muscle exercises are recommended to improve quality of life and sexual function. Biofeedback therapy can have good therapeutic promise as an adjunct to muscle exercise in patients with pelvic floor overactivity by identifying changes in the pelvic floor muscles during chronic pelvic pain. Sexual medicine specialists assess sexual dysfunction with a focus on women and the emotional, sexual and social problems caused by the disease. Engaging in sexual activity and intimacy enhances positive experiences and relieves pain. Caring for the patient, patient explanations, and conveying beliefs and confidence are an effective way to reduce anxiety. Psychological interventions, cognitive-behavioral therapy (hypnotherapy, self-training) can reduce pain and improve quality of life, mood and functioning. Psychological interventions depend on the content and focus of the intervention. Tension-relaxation physiotherapy and emotional catharsis have been reported to be successful in treatment. Myofascial trigger point therapies refer to heat therapy, physical massage, ischemic compression, stretching, anesthetic injections, acupuncture, electrical neuromodulation, progressive muscle relaxation, training, yoga and hypnosis. A team of urologists, physiotherapists and psychologists used the above treatments and as a result more than half of the CPPS patients showed improvement in their symptoms. The efficacy of these treatments still needs to be studied in a large number of controlled studies and by specially trained physicians. The general treatment of CPPS is part of a holistic approach that consists mainly of pharmacological treatment of central and neuropathic pain. The principle of pain medication is to combine drugs, reduce the dose of various drugs, reduce side effects and improve the patient’s quality of life. Paracetamol (paracetamol) is a commonly used antipyretic and analgesic drug that acts on the central nervous system, and there is not much evidence for its effectiveness in the treatment of CPPS. Non-steroidal anti-inflammatory drugs (NSAIDs) are a class of drugs containing salicylic acid that can be tried. Amitriptyline is a commonly used tricyclic antidepressant with a long history of use as an analgesic and validated by evidence-based medicine, but there is no concrete evidence for a therapeutic effect on CPPS. The antispasmodics carbamazepine and gabapentin are effective for neuropathic headache, there have been some general studies on pelvic pain, and individual drugs have been systematically evaluated. The use of opioids must be strictly controlled, taking into account their addictive properties and dependence. Medication should involve a trained physician with expertise in chronic pain management. The choice of any medication needs to be evaluated for pain relief, functional improvement, and side effects. In conclusion, a single treatment will provide only modest symptomatic improvement in patients with CPPS, and better outcomes may be achieved with multiple treatments.