{"paper_id":"3b4c2ff3-1af1-4e45-b06d-4e5e48c7a6d4","body_text":"Abstract\nBackground:\nChronic pelvic pain remains challenging for physicians to manage due to central and peripheral sensitization and multiple pain generators including the bladder, pelvic floor, and pudendal nerve. Pain management providers have used nerve blocks for years for diagnosis and treatment. We developed a desensitization algorithm that provides a stepwise approach to improve patients pain scores.\nMethods:\nThis is a prospective observational cohort study of 182 women aged 15–90 years old with chronic pelvic pain using an algorithm from 2016 to 2018. Treatment started with an Anesthetic Challenge Test of the bladder to guide us through a protocol of intravesical therapy and/or pudendal nerve blocks as a second step.\nResults:\nACT POSITIVE patients, who received intravesical therapy: 84% had a Visual Analog Score pain improvement of at least 50%, 64% improved at least 80% (41% pain-free). Those desiring additional relief that received further Pudendal Blocks: 83% had final improvement of at least 50% (67% pain-free). ACT NEGATIVE patients received Pudendal Blocks with 80% of subjects achieving at least 50% relief, 65% improved at least 80% (35% pain-free). All final groups showed a statistically significance of P < .05% when compared to their initial pain scores.\nConclusion:\nManagement of women with chronic pelvic pain would ideally start with treating a specific diagnosis which, in most cases, is difficult to establish since the majority have more than one pain generator. Our algorithm simplified the approach and reduced the severity of pain scores prior to any further necessary surgical interventions.\nKeywords: Chronic pelvic pain, Endometriosis pain, Painful bladder syndrome, Myofascial pain, Pudendal nerve pain, Central nervous system sensitization, Interstitial cystitis\nINTRODUCTION\nChronic pelvic pain (CPP) is a major public health problem, leading to devastating personal consequences for patients. They often refer a long and frustrating journey through diagnosis and treatment Exclude, due to the persistence of pain. The burden of any chronic pain and its association with social and economic consequences proves it to be a global health priority, requiring emergent global focus on the search for better care.1\nThe most recent review on the prevalence of CPP estimated it to range from 5.7% to 26.6%.2 These numbers may still not reflect reality accurately due to the absence of a single definition, appropriate diagnostic tests, lack of population-based studies dedicated to the prevalence, scarcity of studies, few referrals to specialists, and the paucity of information and education on the subject.2 It accounts for 10% of all gynecologic office visits, 40% of laparoscopies, and 12% of hysterectomies, even though 80% of the patients do not have a gynecologic origin for their pain.3–5 A large-scale population-based study done in 1996 estimated that CPP had a $2.8 billion cost per year with office visits (what would be equivalent to $5.8 billion in 2020) and an indirect cost due to time lost from work of approximately $555.3 million. It leads to time lost from work and reduced productivity in 15% and 45% of patients, respectively.5,6\nFor many decades, end-organ specialists have used disease or organ-based approaches to attempt to determine the cause(s) of pelvic pain. Among the most common etiologies of female pelvic pain are those of gynecologic origin (endometriosis/adenomyosis, pelvic inflammatory disease, endosalpingiosis, adhesions, uterine fibroids, residual ovary and remnant ovary syndrome), urologic origin (cystitis, painful bladder syndrome/interstitial cystitis [PBS/IC], urethral syndrome), gastrointestinal (irritable bowel syndrome [IBS], inflammatory bowel disease, colorectal carcinoma), musculoskeletal (myofascial pain [MFP], fibromyalgia, coccygodynia), and neurologic origin (pudendal neuralgia or neuropathy [PN], psychosomatic/central sensitization disorders).7,8\nA more contemporary concept concerning the pathophysiology of chronic pain should separate neurogenic pain from non-neurogenic pain. Often there is a triggering peripheral nociceptive insult such as surgery, endometriosis, traumatic falls, childbirth, or inflammatory processes that result in peripheral sensitization. The prolonged barrage of noxious stimuli that arrive at the dorsal horn results in a cascade of events leading to central sensitization.9 Therefore, the management of patients is challenging and requires evaluation for multiple peripheral pain generators. Each process identified requires treatment with concurrent down-regulation of the neuropathic changes associated with central sensitization.\nIn our study, CPP patients with allodynia or worsening of their pain during physical examination (hyperalgesia), indicators of central sensitization, were put through a stepwise desensitization algorithm with special attention being placed on pain being generated from the bladder, pelvic floor and pudendal nerve. They all went through an Anesthetic Challenge Test (ACT), the initial evaluation step of our algorithm with the objective to reduce the severity of their pain scores even before necessarily phenotyping their pain.\nMETHODS\nThis is a prospective observational cohort study of 182 women aged 15 to 90 years old with the diagnosis of CPP. They were treated according to the desensitization algorithm at a private practice setting from 2016 until 2018 (Figure 1). The local Institution Review Board was consulted and exempted from the study because the methods included the statistical analysis of a well-established routine treatment of the practice for many years and followed the Declaration of Helsinki principles.\nAll women with a history of CPP, defined as a noncyclical pain that appeared in locations such as the pelvis, anterior abdominal wall, lower back, or buttocks, seen at the pelvic pain center with a minimum time of onset of symptoms of 3–6 months and with pain severe enough to require them to seek medical attention were included. Evaluation started with a complete history and physical. The most common symptoms varied from any combination of the following: pelvic and abdominal pain, low abdominal pain, dysmenorrhea, urinary urgency, frequency, nocturia, incomplete bladder emptying, dyspareunia, low back pain, bladder pain, endometriosis, rectal pain, anxiety, depression, disturbed bowel habits (constipation and/or diarrhea), rectal pain and symptoms of fibromyalgia. A disease or organ-based diagnosis was not part of the inclusion/exclusion criteria. Patients with CPP were enrolled regardless of any combination of previously diagnosed comorbidities such as endometriosis, adenomyosis, MFP syndrome, IBS, IC, uterine fibroids, fibromyalgia, tail bone injury, coccydynia, PN, scoliosis, leg length discrepancy, anxiety, depression, bipolar disorder, migraine, Crohn’s disease, ulcerative colitis, diverticulitis, etc. Determining the prevalence of symptoms or comorbidities was beyond the scope of this study. Moreover, patients could present to the office with any combination of previous treatments such as oophorectomy, oophoroplasty, total abdominal hysterectomy, vaginal hysterectomy, colpopexy, tubal ligation, hemorrhoidectomy, conization, endometriosis ablation surgery, excisional endometriosis surgery, adhesiolysis surgery, ectopic pregnancy removal, cholecystectomy, C-sections, abdominal wall hernia repair, vaginal repair, back/spinal surgeries, sling, etc. Serotonin-norepinephrine reuptake inhibitors, gabapentin or pregabalin were being used by some patients. Preemptively, all patients received education on PBS/IC diet at the first initial visit.10 Possible precipitating factors were sought. Exclusion criteria included UTI and vaginal/pelvic infections, as well as oncologic lesions, pelvic mass or other pathologies that required surgical procedures and were, therefore, immediately sent to surgery.\nA pelvic examination was carried out after patients had been counseled and signed the consent for treatment. The gynecologic examination consisted of using a single digital technique in which careful pelvic pain mapping was done. This examination was always performed by the same examiner with the patient grading on a visual analog scale (VAS) the amount of discomfort experienced as low digital pressure (just enough to change fingernail bed color capillary pulp filling) was applied at the following: perineal body, pubococcygeus muscle bilaterally, obturator internus muscle bilaterally, coccygeus muscle bilaterally and base of bladder (swiping gently towards the sub urethral area). If upon gentle pressure, allodynia or hyperalgesia were present, pain scores for each area were added to reach a total final score that could range from 1 to 80 and was recorded by a medical assistant who was present during all examinations. Additionally, toothpicks were also used to test for pudendal nerve hyperalgesia. This initial step in identifying each pain generator is depicted by the amount of pain experienced in locations that mimic a patient's daily pain during the pelvic examination. The information obtained by the patient's history, questionnaires, physical examination, along with the response to ACT allowed the investigator to determine the next step in the assessment. Furthermore, it allowed for a more comprehensive understanding of each patient’s specific neural sensitization. Therefore, narrowing in not only which pain generators are involved, but also, how and why their CPP is occurring.\nIf the pelvic examination identified hyperalgesia or allodynia which are indicators of central sensitization, the patient was scheduled to go through an ACT of the bladder, a simple in-office procedure that consisted of an urethral catheterization and collection of a sample of urine for urinalysis and culture followed immediately by instillation of a mixture of local anesthetics and heparin (10 ml of .5% bupivacaine, 10 ml of 2% lidocaine, and 2 ml/20.000 UI heparin). Patients were instructed not to void and remain in the examination room to be re-evaluated by the same physician. After 10–15 minutes, a pelvic examination was carried out as previously described. Pre-ACT and Post-ACT VAS scores were compared, and patients were divided into two groups according to their response: ACT POSITIVE group (those with a decrease on VAS score of 30% or more) and ACT NEGATIVE group (with a decrease on VAS score of less than 30%). This 30% decrease cutoff is reasoned by 25 years of clinical experience where a 30% reduction proved to be the minimum of initial improvement of pain observed in patients recognizing a significant improvement in their pain upon completion of intravesical therapy (IVT).\nIf patients had a significant improvement with ACT (ACT POSITIVE group), they started IVT, a process of nerve desensitization that consisted of bladder rinses scheduled twice or three times a week until a total of 8 to 10 procedures. A bladder rinse is the basis of the IVT in which the procedure is the same as the ACT, containing the same mixture, but it is used more as a systematic therapy. After every 4 rinses, a new sample of urine was always collected to rule out any iatrogenic infection from the catheterizations. At the end of IVT, a pelvic examination was done, and Pre-ACT and Post-IVT VAS scores were compared. Utilizing their response to IVT, patients were divided into two groups according to their response to treatment: Intravesical Therapy POSITIVE group (those with a decrease on VAS score of 30% or more) and Intravesical Therapy NEGATIVE group (those with a decrease on VAS score of less than 30%) (Figure 1).\nPatients in Intravesical Therapy POSITIVE group were managed depending on their pain improvement. Those with significant symptom improvement or those sufficiently satisfied with their results discontinued treatment, allowing us to calculate their final total improvement (Group A; Figure 1). Patients still seeking for additional improvement in pain (Group B; Figure 1), were offered the second step of the algorithm: a series of 3 unilateral or bilateral pudendal nerve blocks (depending on whether the pain was unilateral or bilateral) under fluoroscopy in an outpatient setting that was scheduled every 3 to 4 weeks. The block was consistently placed approximately 2 cm medial to the ischial spine, using a vaginal technique and under sedation with propofol. The 1:1 mixture solution consisted of 10 ml of 1% lidocaine, 10 ml .5% bupivacaine, 1 ml of gentamicin 30 mg/ml, 1 ml triamcinolone 10 mg/ml and 2 ml of radiologic contrast, forming a 24 ml mixture solution. The block was applied on both the right and left pudendal nerve. After the block, x-rays showed the solution with contrast spread throughout the coccygeus muscle area, confirming it to be successful. Immediately after the procedure, after waking up from the anesthesia, all patients stated their pain was gone. Patients were reevaluated within the first 7–10 days after each block to examine recovery and pain improvement. The improvement was both a therapeutic and diagnostic response. After the series of three blocks were completed, a pelvic examination was performed Pre-ACT and Post-Block VAS scores were compared, and the final total improvement was recorded (Figure 1, Group III).\nPatients who experienced little benefit with IVT (Intravesical Therapy NEGATIVE group) were encouraged to go through a series of desensitizing pudendal nerve blocks as described above. Pre-ACT and Post-Block VAS scores were compared, and final total improvement was recorded (Figure 1, Group II).\nIf patients in ACT POSITIVE group that were offered IVT, found catheterization particularly uncomfortable, they were encouraged to start the series of desensitizing pudendal nerve blocks, instead. After the series of three blocks were completed, a pelvic examination was done, and Pre-ACT and Post-Blocks VAS scores were compared to quantify final total improvement (Figure 1, Group IV).\nPatients in the ACT NEGATIVE group (less than 30% improvement in their VAS pain score) were scheduled for the series of desensitizing pudendal nerve blocks as described above. After the series of three blocks were completed, a new pelvic examination was done, and Pre-ACT and Post-Blocks VAS scores were compared to quantify final total improvement (Figure 1, Group I).\nAn exploratory and descriptive analysis was carried out for discrete quantitative response variables (pain scores) between the groups: Pre-ACT x Post-ACT POSITIVE; Pre-ACT x Post-ACT NEGATIVE; Pre-ACT x Post-IVT; Pre-ACT x Post-IVT INTRAVESICAL THERAPY POSITIVE; Pre-ACT x Post-IVT INTRAVESICAL THERAPY NEGATIVE; Pre-ACT x Post-IVT GROUP A; Pre-ACT x Post-IVT GROUP B; Pre-ACT x Post-Block Group III; Post-IVT GROUP B x Post-Block Group III; Pre-ACT x Post-Block Group II; Post-IVT INTRAVESICAL THERAPY NEGATIVE x Post-Block Group II; Pre-ACT and Post-Block GROUP IV; Pre-ACT and Post-Block GROUP I.\nTo test the null hypothesis (that there was no significant difference between treatments according to the description of the groups), we used the one-way ANOVA test. The finding of a difference by the test indicates that samples differ in the study variable. The significances were assessed by comparing the patient's initial degree of pain (before any intervention) with the reported final degree of pain after the end of the proposed treatment. Furthermore, the statistical difference between the groups that finished treatment was evaluated, to assess whether the improvement in pain between them was similar or not.\nRESULTS\nThe study enrolled 182 patients that had complete medical records, therefore their scores pre and post interventions could be compared (Figure 2). Patient’s Pre-ACT VAS scores ranged from 1 to 70. Pre-ACT’s Box-plot analysis showed 50% of patients had VAS score greater than 10 and less than 35 (Figure 3).\nAfter ACT test, 145 subjects (80%) had a pain score decrease of 30% or more. Thus, they were categorized in what we called ACT POSITIVE group (Figure 2, ACT POSITIVE). The boxplot analysis depicts up to 50% of patients had final pain scores lower than 10, indicating improvement in pain compared to Pre-ACT scores. There was a significant difference between Pre-ACT and Post-ACT POSITIVE group VAS scores (P = 2.28e−06), showing the intervention was efficient in reducing pain (Figure 4, ACT POSITIVE).\nIn the ACT POSITIVE group, 44 patients discontinued mainly due to health insurance issues, personal preferences and/or geographical distance to the office. The remaining 93 patients completed the series of IVT recommended and were categorized into INTRAVESICAL THERAPY group (Figure 2, Intravesical Therapy). In the Post-IVT group, 50% of patients had VAS score less than 10 and 25% were painless. Pre-ACT and Post-IVT VAS scores were compared and there was a significant difference (P = 2.0e−16), showing that treatment was efficient in reducing pain (Figure 4, Intravesical Therapy).\nOut of the 93 patients in the INTRAVESICAL THERAPY group, 80 patients (86%) had a decrease of 30% or more on VAS and were, therefore, categorized into INTRAVESICAL THERAPY POSITIVE group and the 13 patients (14%) that had a decrease of less than 30% on VAS were categorized in the INTRAVESICAL THERAPY NEGATIVE group (Figure 2).\nThe 80 patients categorized into INTRAVESICAL THERAPY POSITIVE group had an average improvement of 76%, among them: 67 (84%) had a decrease of 50% or more, out of which: 51 (64%) had more than 80% improvement and 33 (41%) were pain-free (Figure 2, Intravesical Therapy POSITIVE). Boxplot analysis (Pre-ACT x Post-IVT INTRAVESICAL THERAPY POSITIVE group) showed 50% of patients with scores less than 5, indicating improvement in pain compared to Pre-ACT. There was a significant difference between the groups (P = 2e−16) (Figure 4, Intravesical Therapy POSITIVE).\nFurthermore, out of the 80 patients in the INTRAVESICAL THERAPY POSITIVE group, 57 (71%) decided to discontinue the treatment at this point due to satisfactory relief: 42 of these patients (74%) had a decrease on VAS of 80%, out of which 32 (56%) were pain-free. The average improvement on the 57 patients that discontinued was of 86% (Figure 2, Group A). Boxplot analysis (Pre-ACT and Post-IVT GROUP A) showed less variability on pain scores with 50% of patients either pain-free or with scores less than 5. Further analysis comparing the groups showed a significant difference between them (P = 2e−16) (Figure 4, Group A).\nThe remaining 23 patients (29%) in the INTRAVESICAL THERAPY POSITIVE group had significant relief but had interest in further improvement and were assigned to GROUP B. Therefore, they were offered the series of pudendal blocks. Their Post-IVT GROUP B (Pre-Block) VAS scores showed 6 (26%) with a decrease on VAS between 30%–50%, 17 (73%) patients with more than 50% improvement, out of which 9 (39%) had improved more than 80% and only 1 was pain-free. The average improvement of GROUP B was of 66% (Figure 2, Group B). Boxplot analysis (Pre-ACT x Post-IVT GROUP B) showed 50% of patients with VAS score lower than 10, indicating improvement up to this point. There was a significant difference between the groups (P = 3.07e−07) (Figure 4, Group B).\nThree GROUP B’s patients failed to complete the full series of pudendal nerve blocks due to health insurance issues, personal preferences and/or geographical distance to the office. Twenty patients finished treatment and had their Pre-ACT and Post-Block GROUP III VAS scores compared: 18 patients (90%) had more than 50% improvement out of which, 12 patients (60%) had 80% improvement or more, and 6 (30%) were pain-free. The average improvement of this group was of 77% (Figure 2, Group III). Boxplot analysis (Pre-ACT X Post-Block GROUP III) showed 50% of patients with scores less than 10. There was a significant difference between the groups (P = 7.57e−09) (Figure 4, Group III). Although patients stated they had further satisfactory improvement when comparing their pain status Post-IVT GROUP B x Post-Block GROUP III (with boxplot analysis showing that 50% of patients had further improvement, with some being pain free), there was no significant difference between the groups (P = .146) (Figure 5).\nIn the Intravesical Therapy NEGATIVE group: six patients did not proceed with desensitizing blocks mainly due to health insurance issues, personal preferences and/or geographical distance to the office and seven were submitted to the blocks. One discontinued, after having started blocks, due to the same hinderances. Six patients finished treatment and had their Pre-ACT and Post-Block GROUP II VAS scores compared: 5 patients (83%) decreased more than 50% on VAS among which 4 (67%) were pain-free. The average improvement of this group was of 82% (Figure 2, Group II). Boxplot analysis showed that 50% of Group II patients were either pain-free or with pain scores less than 5. Further analysis showed a significant improvement when comparing final Post-Block GROUP II scores to either their Pre-ACT scores (P = .000155) (Figure 4, Group II) or to their Post-IVT INTRAVESICAL THERAPY NEGATIVE (Pre-Block) scores (P = .000256) (Figure 6).\nOut of the 145 patients on the ACT POSITIVE group, 8 requested to proceed directly to pudendal blocks, instead of going through IVT, due to insurance reimbursement issues, personal preferences, or uncomfortable catheterization. Pre-ACT and Post-Block GROUP IV VAS scores were compared: 7 (88%) showed a decrease greater than 50%, out of which 6 patients (75%), had a decrease of 80% or more and 3 patients (38%) were pain-free. The average improvement of this group was of 85% (Figure 2, Group IV). Boxplot analysis (Pre-ACT x Post-Block GROUP IV) showed 50% of patients with pain scores below 5. There was a significant difference between the groups (P = 4.04e−05) (Figure 4, Group IV).\nAfter the ACT, 37 subjects (20%) had less than 30% decrease on their VAS score and were, therefore, categorized into the ACT NEGATIVE group (Figure 2, ACT NEGATIVE). Analysis showed there was no significant difference between Pre-ACT and Post-ACT NEGATIVE pain scores (P = .413). Boxplot showed 50% of subjects referring VAS score greater than 15 and less than 35 (Figure 4, ACT NEGATIVE).\nOut of the 37 patients on ACT NEGATIVE group: 12 discontinued mainly due to health insurance issues, personal preferences and/or geographical distance to the office; 25 went straight to PB. After having started blocks, 5 patients discontinued due to the same reasons listed above. Twenty patients finished treatment and had their Pre-ACT and Post-Block GROUP I VAS compared: 1 patient had a decrease of less than 30%, 3 (15%) had 30%–50% decrease, 16 patients (80%) had at least 50% decrease, out of which 13 patients (65%) had a decrease of 80% or more and 7 were pain-free. The average improvement of this group was of 80% (Figure 2, Group I). Boxplot analysis observed 50% of patients with VAS of 20 or less. Further analysis showed significant difference between groups (P = 2.28e−06) (Figure 4, Group I).\nAll final groups (A, I, II, III and IV) had a statistically significant improvement on pain scores when compared to their Pre-ACT scores. Boxplot analysis showed the group with the most improvement was Group A followed by groups II, IV, III and I, respectively, as can be observed in Figures 7 and 8.\nPatients in Group A underwent the greatest improvement by undergoing IVT after a positive ACT test. Thus, there was no clinical indication for further pudendal blocks. Those in Group II, the second-best group, had a positive ACT, but were showing no improvement of pain after IVT therapy. After getting a series of pudendal blocks, they finally reached adequate improvement. Group IV, the third best group, had patients with a positive ACT that deferred IVT treatment and went forward to pudendal blocks. Group III, the fourth best, had also a positive ACT with insufficient improvement after IVT therapy, therefore moved on to pudendal blocks. Patients in Group I, fifth best group, had a negative ACT and went through pudendal blocks. The boxplot analysis shows that pudendal blocks were more efficient on the groups that started with an ACT POSITIVE test when compared with ACT NEGATIVE patients.\nOut of the 54 people that had pudendal blocks, vaginal bleeding was identified immediately in 4 of them most likely due to needle perforation of vaginal arteries. Two had hematomas identified during postblock that were self-containing and required no further interventions. These patients still showed improvement on pain scores and proceeded with subsequent treatment.\nNo patients required any reintervention during the 3–4 month follow up visits. Out of 54 patients that finished the series of blocks, six patients requested a reinjection of pudendal block by the sixth month follow-up due to flare-up of their pain, indicating they needed another bladder rinse which we termed a 'rescue' rinse.\nDISCUSSION\nManagement of pelvic pain can be challenging due to the overlapping symptoms present in multiple different pain syndromes.9 Identifying a single initial insult can be complex when the mechanism of chronic pain is mainly ignited by many interconnected “neuronal pathways” involved in the cascade of events ultimately leading to neurosensitization.11 Even if an initial trigger has already been eradicated, such as endometriosis, pain may still persist due to the cascade of events thar result in permanent central sensitization.\nEndometriosis, a chronic inflammatory estrogen-dependent disease, can be a cause of nociceptive visceral pain. It is likely that its pain mechanism merges all three types of pain: nociceptive, inflammatory, and neuropathic.7,8,12 Once ectopic endometrial tissue responds to hormones, pain varies over the menstrual cycle.11 Even women without endometriosis have increased pain scores during menses if they have central sensitization. Although studies have showed improvement of pain scores with the removal of endometriosis, incomplete relief may be experienced in some cases.7 The neuropathic mechanism highlighted above may explain why some patients continue experiencing pain even after the removal of the primary lesion.7 Underlying causes may be present such as PN. This suggests that even the most skilled surgeon, after removing all the endometriosis, may not have helped entirely to improve patients’ pain. Until all other pain generators are identified and treated, the dorsal horn may not be able to down-regulate the sensory processing nor the neuropathic output states.13\nA study published by our group in 2002, using concurrent laparoscopy, cystoscopy with hydrodistension and the potassium challenge test, showed that over 90% of CPP patients had PBS/IC and 80% had endometriosis. The co-occurrence of the two conditions was calculated to happen in as many as 70% of them.14 Two years later, up to 38% of patients presented persistent posthysterectomy CPP. A study was done to investigate the prevalence of bladder-origin pain in these patients. It was found that approximately 80% of patients had bladder dysfunction that showed improvement with treatment, postulating that these women may have had bladder symptoms initially. These patients could have been benefited of a thorough investigation and bladder-pain oriented treatment before hysterectomy.15 Surgeries, especially those associated with complications (infections, injuries, etc.), are a source of noxious stimuli (inflammation due to nerve and tissue damage inherent to any surgical procedure) that can up-regulate the dorsal horn and worsen up the neuropathic mechanism or even initiate it.16 There can be a postoperative windup taking months to manifest itself. Therefore, it may not be acknowledged at the initial routine postoperative visits to the office.13 A recent systematic review showed that 61% of patients with CPP had PBS/IC, 70% had endometriosis and 48% had both diagnosis.17 Failing to acknowledge these numbers may delay the proper treatment, leading to repeated surgical procedures and futile hysterectomies.14 It’s important to acknowledge that symptoms of IC may mimic gynecologic disorders including voiding symptoms, dyspareunia, flare-ups after sexual activities and perimenstrual exacerbations of pain.15\nThe symptoms ascribed to “endometriosis” may not respond to conventional therapies for endometriosis if neuropathic etiologies are overlooked. PBS/IC needs to be frequently thought of as a possible underlying cause found concurrently with other pathologies such as pudendal neuropathy, thoracolumbar junction syndrome, and MFP.18 MFP is present in as many as 20%–85% of CPP patients.7,13 with the presence of trigger points (taut muscle bundles that present tender on pressure) as the most common presentation.7\nPhenotyping patients with IC/bladder pain syndrome has led to a deeper understanding of CPP, aiding in the identification of appropriate targets for an individualized therapeutic approach. Phenotyping all forms of CPP may potentially be a daunting process that could be eased by separating neurogenic from non-neurogenic causes. The algorithm guides us through identifying the presence or absence of common pain generators seen in pelvic pain disorders. It attempts to identify and treat bladder pain as well as pelvic floor myalgia. A series of desensitizing procedures involving lidocaine and bupivacaine instilled within the bladder (seeking to reduce noxious stimuli coming from the bladder) and/or injected perineurally to the pudendal nerve, blocks noxious stimuli arising from any source of pain innervated by the pudendal nerve (or additional pelvic neuropathic pain generators) providing the ability to reduce the noxious stimuli arriving at the dorsal horn. This reduction of noxious stimuli appears to down-regulate the nociplastic changes that have occurred because of central sensitization. It is important to state that benefit seen from a series of pudendal blocks does not necessarily establish the diagnosis of PN but, instead, simply clarifies that those patients have a pain generator whose noxious stimuli is carried through the branches of the pudendal nerve.19,20 A definite diagnosis of PN can be readily made without the use of pudendal nerve blocks.21,22 A simple pinprick examination of the six pudendal nerve branches is crucial to a successful CPP physical examination.23,24\nOne of the strengths of this study is the utilization of a simple desensitization treatment that downgrades patient’s pain and helps the provider to phenotype or identify common pain generators involved in most patients with CPP starting with an ACT test: a simple, noninvasive, inexpensive, safe, and effective procedure that sorts out the patients that likely would benefit from IVT from those who would benefit better by the series of pudendal nerve blocks. CPP treatment is within the scope of the general gynecologist who could use this diagnostic and therapeutic algorithm, provided they have proper training on the examination of the pelvic floor and the pudendal block technique. Patients with bladder-centered symptoms and findings may be more likely to obtain sufficient relief with IVT alone. These patients have the potential of decreasing their pain scores in at least 50% in 84% of the cases (out of which 64% may improve more than 80% and 41% may finish treatment pain-free without the need for more invasive procedures). At the end of IVT, patients are evaluated to see whether pudendal nerve blocks, a more invasive procedure, are indicated (in 29% of the cases). This desensitizing treatment has been used successfully for many years in our practice to immediately seek for relief, even if characterization of the underlying insult or syndrome causing CPP was unclear. Patient’s pain can be addressed immediately, without any delays. Further investigation or concurrent diagnostic tests can be run while the patients are being desensitized. It showed us that, regardless of the comorbidities or of any combination of them, and that regardless of symptoms or any combination of symptoms, patients with CPP could experience improvement on pain scores by the end of the desensitization treatment. Upon completion of this algorithm, our numbers show that 86% of patients had an improvement of at least 50% on their pelvic pain scores (out of which 69% had at least 80% improvement and 46% were pain-free), which is a significant finding.\nThe limitations of this study include our inability to determine the duration of benefit that patients achieved after the completion of this algorithm, beyond 6 months. It was done in a private setting, without funding, what made factors such as health insurance, financial and geographical location issues impair the continuation of a number of patients. Only 111 out of 182 patients finished the algorithm. A final limitation to this treatment is that it may not provide benefit from pain generated from outside of the pelvis such as diffuse fibromyalgia, orthopedic issues involving the back or hips, or neuropathic pain arising from areas outside the distribution of the pudendal nerve. This emphasizes the need for long-term medications and the necessity for continued research on the failures of the interventions we provided. However, with such a marked reduction of pelvic pain scores, we were able to locate pain generators outside of the pelvis easier.\nCONCLUSION\nGiven our present understanding of chronic pain, the old concepts of organ-based and disease-based chronic pain treatment must be abandoned and replaced by a new paradigm that includes separating neurogenic from non-neurogenic pain. The current understanding of pelvic pain needs to include concepts of noxious stimuli cumulatively producing a neuropathic upregulation located both at the periphery (peripheral sensitization) as well as centrally, especially the dorsal horn of the sacral region (central sensitization, nociplasticity). This typically will trigger multiple pain generators. Thus, the clinician must remember that even if we can identify an original trigger of the pain disorder, neuropathic pain may persist. The authors have presented a simple diagnostic and therapeutic algorithm to help desensitize both the peripheral and central areas involved in a patient's CPP syndrome. It can be used by health care providers as the initial work-up of patients with CPP as a triage tool and a guide for initial management. By utilizing this simple algorithm not only we could make most CPP patients achieve significant pain relief prior to any surgical intervention, but also, we could potentially reduce flare-ups of postoperative pain and reduce unnecessary multiple surgeries.\nFootnotes\nDisclosure: none.\nConflict of interests: none.\nFunding sources: none.\nInformed consent: Dr. Rogério declares that written informed consent was obtained from the patients addressing the purpose of data collection for the study.\nContributor Information\nLiane Silva Rafael Rogério, Clínica Aurora, Manaus, Amazonas, Brazil..\nMaurice K. Chung, Professor, Director, Center of Endometriosis, Pelvic Pain and Urogynecology, Wheeling, West Virginia, USA..\nCharles W. Butrick, Female Pelvic Medicine and Reconstructive Surgery, Urogynecology of Kansas City, Overland Park, Kansas, USA..\nStanley J. 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