Orofacial pain affects 10–15% of adults, yet treatments are limited. The gaps in care are frustrating for both patients and providers and can negatively impact patient–provider interactions. These interactions are key because they impact patient-reported outcomes and satisfaction with care. Purpose: Our study aims to understand the nuanced experiences with medical providers among patients with orofacial pain. Methods: In a cross-sectional survey, 260 patients provided written responses describing their experiences with medical providers. Using an inductive–deductive approach to thematic analysis, we identified themes and subthemes and organized them into four domains based on the Patient-Centered Model of Communication. Results: Patients reported feeling hopeless about treatment options, frustrated with lack of provider knowledge, disappointed in ineffective care, and stigmatized and dismissed by providers. Patients also said they learned to advocate for their health, were grateful for effective care, and felt lucky when providers listened and showed compassion. Patients identified key barriers that interfere with care . Conclusions: Findings can help inform training programs and psychoeducation that target patient–provider communication to improve patient-reported outcomes, the quality of care delivered, and health care utilization and costs. Chronic orofacial pain is an umbrella term for persistent pain (≥15 days in per month and lasting >3 months) in the face, mouth, or jaw , accordiAcross primary care and dental settings, providers report feeling uncertain and ill-equipped to diagnose and treat orofacial pain . A recenPatient-centered communication (PCC) is widely endorsed as necessary for high-quality, patient-centered care . The PatThe purpose of this study was to understand patients’ experiences with medical providers when they present with orofacial pain. Informed by the Patient-Centered Model of Communication , our aimWe conducted a qualitative secondary analysis using a large cross-sectional survey on adults’ experiences living with chronic orofacial pain. We analyzed data from an open-ended question asking participants about their experiences with medical providers. Massachusetts General Hospital Institutional Review Board approved all study procedures.N = 260). We classified self-reported diagnoses based on ICOP criteria . I could list countless treatments and procedures that have been offered to me that have been denied, but they will pay for the tons of medication I take!” At times, patients relied on emergency room visits for acute pain relief when they could not afford consistent outpatient treatment. Patients also endorsed challenges with transportation and logistical barriers to seeing providers. Because of the lack of specialists in orofacial pain, patients often had to travel far distances to receive care, which is challenging for those with limited resources. Because specialists are rare, patients said it was difficult to establish care with a new provider when they moved locations.Patients described how challenging it was to coordinate multiple providers. When patients had a team of multidisciplinary providers, they often were not coordinated in their care. One participant explained, “There is never any team management and there is a real disconnect between my GP, neurologist, pain [doctor], and psychologist”. Patients felt as if they were seeking individual consultations and had to streamline their own treatment plan. Patients reported that sometimes they had to manage disagreement among providers and decide which advice to follow when recommendations conflicted. Additionally, some patients were disappointed that their providers did not offer mental health resources. They expressed desire for their teams to be more cohesive and collaborative.Patients reported that finding orofacial pain specialists was challenging. They spent many years seeing many different providers—some successful, others unsuccessful. As one participant described, “Finding doctors to, first, believe me, then get a correct diagnosis. Second was the years of trial and error with medications”. Identifying providers who were both knowledgeable and able to treat orofacial pain was challenging and often distressing. For example, a participant said, “Finding a provider knowledgeable about the TMJ is rare. Finding one with TMD knowledge is a unicorn”. The lack of specialized providers created significant emotional distress for patients. One participated shared, “Early on, I may have seen 20 or more doctors that were unable to diagnose my condition, many that were downright rude. This nonsense went on for several years to the point that I no longer wanted to live. I now have a pain doctor that has helped me somewhat get my life back”. Patients highlighted the emotional cost associated with limited resources for their condition including stress, anxiety, depression, and isolation.Although ~10–15% of adults experience orofacial pain , diagnospatient factors, patients with orofacial pain often felt hopeless about treatments given their history of failed attempts and the lack of understanding from providers about their pain. Patients explained that this hopelessness led to avoidance in continuing to seek care. This aligns with prior literature indicating that patients with orofacial pain often fail to see improvements despite multiple appointments with a variety of providers  prayers”. These varied experiences emphasize the need for standardized patient-centered care. Training and psychoeducation programs for providers may help to improve understanding of patient experiences, communication, and multidisciplinary team coordination.


Background: The optimal dosage for opioids given to patients after surgery for pain management remains controversial. We examined the association of higher post-surgical opioid use with pain relief and recovery. Methods: We retrospectively enrolled adult patients who underwent elective abdominal surgery at our hospital between August 2021 and April 2022. Patients were divided into the “high-intensity” or “low-intensity” groups based on their post-surgical opioid use. Generalized estimating equation models were used to assess the associations between pain scores at rest and during movement on days 1, 2, 3, and 5 after surgery as primary outcomes. The self-reported recovery and incidence of adverse events were analyzed as secondary outcomes. Results: Among the 1170 patients in the final analysis, 293 were in the high-intensity group. Patients in the high-intensity group received nearly double the amount of oral morphine equivalents per day compared to those in the low-intensity group (84.52 vs. 43.80), with a mean difference of 40.72  oral morphine equivalents per day. At all timepoints, the high-intensity group reported significantly higher pain scores at rest  and during movement  as well as significantly lower recovery scores (mean difference (MD) −8.65; 95% CI, −10.55 to −6.67; p < 0.001). A post hoc analysis found that patients with moderate to severe pain during movement were more likely to receive postoperative high-intensity opioid use. Furthermore, patients in the non-high-intensity group got out of bed sooner , required urine catheters for shorter periods of time , and were hospitalized for shorter periods . The high-intensity group was at a higher risk of chronic postsurgical pain . Conclusions: High-intensity opioid use after elective abdominal surgery may not be sufficient for improving pain management or the quality of recovery compared to non-high-intensity use. Our results strengthen the argument for a multimodal approach that does not rely so heavily on opioids. Acute pain occurs after almost every type of surgery . The incOpioids are the primary pharmacological treatment for acute postoperative pain ,6. Most Determining the appropriate amount of opioids is complicated because of differences in typical pain management after various types of surgery and because patients can differ widely in pain thresholds. Studies have compared low- and high-intensity dose regimes, but the samples have been small, and follow-up studies are short, and they may not have involved truly high-intensity doses ,13. ThusWe hypothesized that high-intensity opioid use would not improve pain after abdominal surgery significantly better than non-high intensity opioids. Therefore, we addressed this question by comparing the self-reported postoperative pain and quality of recovery scores between patients subjected to high- or non-high intensity dose regimes after abdominal surgery at our medical center.This study was approved by the Biomedical Research Ethics Committee of West China Hospital (2022–863), which waived the requirement for written informed consent due to the retrospective nature of the study. The present study was conducted and reported in accordance with the guidelines of the STrengthening the Reporting of OBservational studies in Epidemiology (STROBE) .This was a retrospective study of 1240 adult patients who underwent elective abdominal surgery under general anesthesia at the West China Hospital of Sichuan University from August 2021 to April 2022. We included patients >18 years of age who were classified with a physical status of I–III according to the American Society of Anesthesiologists (ASA)’s scale. Patients were excluded if they (1) lacked postoperative pain scores within 5 days after surgery, (2) were transferred to the intensive care unit after surgery, or (3) used more than 60 mg/day OME for 30 days prior to the operation (according to the FDA defines of an opioid-tolerant patient) .The following sociodemographic and clinical data were extracted from electronic medical records: birth year, sex, height, and weight and a history of somatic diseases, ASA class, preoperative analgesic use, surgical information , anesthesia method, and postoperative analgesia regimes. Pain intensity scores were assessed at postoperative days 1, 2, 3, and 5 at rest and with movement, using a numerical rating scale, and were collected from nurses’ documentation and averaged per post-operative day. The patients’ quality of recovery was obtained from the Quality of Recovery—15 questionnaire  , which iIn the present study, postoperative opioids included sufentanil, fentanyl, pethidine, oxycodone, dezocine, tramadol, and hydromorphone. To be able to compare the intensity levels of postoperative prescriptions, we computed the OME (mg/day) by multiplying an opioid-specific conversion factor by the drug dose and quantity supplied . The totCalculation of OME daily dose (mg/day) = [Total opioid dose (within postoperative 5 days) × Conversion factor]/5 daysThe average daily OME in the upper quartile of opioid utilization is defined as “high-intensity” opioid utilization ,18.The primary outcome was the acute pain scores as reported by the patient. Pain at rest and during movement was assessed at postoperative days 1, 2, 3, and 5 using a scale from 0 to 10, with 0 signifying “no pain” and 10 signifying “extreme pain” .Secondary outcomes included the quality of recovery, the incidence of adverse outcomes, and the incidence of chronic postsurgical pain (CPSP). The quality of recovery was assessed at postoperative day 5 using the patient-reported Quality of Recovery—15 questionnaire (QoR-15) . Scores t-test or the Wilcoxon rank-sum test if the data were skewed. Qualitative data were compared using a chi-square test or Fisher’s exact test where appropriate.Continuous variables were reported as mean + standard deviation (SD) or as median and interquartile range (IQR), while categorical variables were expressed as number and percentage. Intergroup differences in continuous variables were assessed for significance using Student’s p-value was adjusted using Bonferroni adjustments (0.05/2) for two primary outcomes. A p-value less than 0.025 was considered significant for the primary outcome. Then, we conducted a post hoc analysis to evaluate risk factors for “high-intensity” use. Variables with p < 0.15 in the univariate analysis and the severity of postoperative pain were entered into multivariate logistic regression.For acute pain, numerical rating scale pain scores at rest and with movement at 1 day and 2, 3, and 5 days after surgery were compared between the groups using regression based on a generalized estimating equations approach, with exposure group and time  as fixed effects and the participant as a random effect. An unstructured correlation model was used. The fully adjusted marginal means of pain scores aggregated across all time points were reported separately by group, with contrast for the difference in groups and 95% confidence interval (CI). We further explored the associations of non-high- or high-intensity opioid use and moderate-to-severe pain using logistic regression models. In all models, we adjusted for age (as a continuous variable) and sex (men or women). Body mass index (BMI) was constructed from height and weight measured at the initial assessment center visit. Preoperative comorbidity, preoperative analgesic use, location of surgery , the type of surgery (open or laparoscopic), ASA physical class (I–II or >III), perioperative management , local infiltration (yes or no), the dosage of sufentanil and remifentanil), duration of surgery (as a continuous variable), and PCIA (yes or no) were extracted. The During the peer-review process, reviewers suggested that a group analysis on the type of surgery should be added due to the observation that patients who received high-intensity opioids were more likely to undergo open surgery than laparoscopic surgery. Three-way repeated measures repeated measures analysis of variance (ANOVA) was used to observe the effect of exposure (high- or non-high intensity opioid use) and the type of surgery (open or laparoscopic) on the outcome variable . In the model, the exposure groups and type of surgery were considered as between-subjects factors, whereas time  was considered as within-subjects factor.As the quality of recovery, we examined the association between patients with “high-” versus “non-high-intensity” opioids use after surgery and the QoR-15 scores using median regression models, and the associations are represented as differences and their 95% CI. For other secondary outcomes, the association test was compared by logistic regression or median regression models with fully adjusted covariates.p-value less than 0.05 in those outcomes should be interpreted as suggestive. All statistical hypothesis tests were two-sided. All the analyses were performed with R software, version 4.2.1 .There was no plan for the adjustment of the width of confidence intervals for multiple comparisons in the analyses of secondary outcomes. A No statistical power calculation was conducted before the study. The sample size was based on the available data. We performed a post hoc analysis to assess the effect size that we could detect based on actual data. With our current sample size, we had 80% power at a two-sided alpha level of 0.05 to detect a greater than 0.4-point difference in numerical rating scale pain scores at rest or during movement on postoperative day 1, 2, 3, or 5 between the two groups.Of the 1240 patients retrospectively identified, 12 were excluded because their ASA classification was over III, 21 were excluded because they were transferred to the intensive care unit, and 37 were excluded due to inadequate data or loss to follow-up. The final analysis included 1170 patients  with a median age of 55 years  received high-intensity opioids after surgery. On average, the high-intensity group received nearly double the daily OME as compared to the non-high-intensity group (84.52 vs. 43.80), corresponding to a mean difference (MD) of 40.72 mg/day OME .One-quarter of patients (p = 0.018) and more likely to undergo open surgery than laparoscopic surgery  in the lower abdomen , and their surgeries lasted longer . Significantly more patients in the non-high-intensity group were treated with nonsteroidal anti-inflammatory agents (NSAIDs) on preoperative day 1  and within 5 days after surgery. Multiple analgesics  were administered for a greater proportion of high-intensity patients than non-high-intensity patients , with movement . Generalized estimation equations showed that patients in the high-intensity group were significantly more likely to report higher pain scores at 1, 2, 3, and 5 days after surgery even if the difference in pain was clinically small  or NSAIDs administration at preoperative day 1  could reduce the risk of postoperative high-intensity opioid use.The post hoc analysis found that patients with moderate to severe pain during movement on postoperative days 1, 2, 3, and 5 were more likely to receive high-intensity opioid use . Howeverp = 0.148; p = 0.121; A post hoc analysis suggested by a reviewer found that there was no interactions between exposure and the type of surgery on the pain score at rest , which was clinically significant . The difference after adjusting for potential confounders was an MD of −8.65 , a difference that was clinically small (p < 0.001) and longer hospitalization after surgery . CPSP occurred in 113 of 293 patients (38.57%) that were given high-intensity opioids compared to 240 of 877 patients (27.37%) given non-high-intensity opioids. These proportions were significantly different after adjusting for potential confounders . In contrast, the two groups did not differ significantly in the incidence of PONV or pruritus.Patients in the high-intensity group took longer to get out of bed after surgery  have been used for patients following orthopedic surgery . Our stuOpioids are one of the most effective analgesics for moderate to severe post-operative pain . HoweverDespite the common use of opioids for managing postoperative pain, clinical guidelines with opioid-sparing measures are emerging ,26. PatiWe acknowledge several limitations in our study. First, the difference in postoperative opioids utilization for patients receiving treatment from “high-intensity”—roughly 40.72 OME per day during a 5-day period, which corresponds to approximately one and one-third morphine tablets per day—may not indicate that the patient with high doses of opioid use had been receiving doses that were sufficiently large enough to place the patient at a poorer quality of recovery and severe pain. Second, our study included only patients who underwent elective abdominal surgery, which may limit the generalizability of our results. Moreover, in the current study, the median age of patients was 55 years , and more patients received open surgeries instead of laparoscopic surgeries; this may represent a selective bias, and our results need to be interpreted with caution. Third, we assessed pain levels and recovery only until 5 days after surgery, and we did not analyze additional outcomes within the first 24 h, so future studies should address these limitations in order to verify and extend our findings. Furthermore, postoperative pain was measured by a self-reported numeric rating scale in the current study. Using objective measurements is warranted to validate or refute our findings. For example, utilizing the bioimpedance methodology from the three-dimensional exploration of nociception  or the nHigh-intensity opioid use after elective abdominal surgery may not be sufficient for improving pain outcomes or recovery compared to non-high-intensity use. Future research should explore opioid prescriptions across a range of surgeries and quantify the thresholds of overuse in order to help inform clinical guidelines for postoperative pain management. Less may be better, but the jury is still out.


Conclusion: EUS-guided botox injection into the internal sphincter appears to be a promising technique for patients with refractory anal fissure with pain.Background: Anal fissures cause severe pain and can be difficult to treat. Medical therapy is initially used, followed by sigmoidoscopy-guided botox injections if the medical therapy is not successful. With this technique, however, it is not clear whether botox is injected into the muscle layer or submucosa. Aim: To evaluate the efficacy of EUS-guided botox injection directly into the internal sphincter. Methods: Consecutive patients with chronic anal fissure refractory to conventional endoscopic botulinum toxin type A injection were enrolled in the study. EUS was performed using a linear array echoendoscope, and a 25 G needle was used to inject botox. All patients were followed up at one- and two-month intervals. Results: Eight patients with chronic anal fissures were included in the study. Six patients had an excellent response to botox at the two-month interval using a visual analog pain scale, while one patient had a moderate response with a pain score reduction of 40%. One patient had no response. No complications were noted. An improvement in visual analog scale (pre-score > post-score) was statistically significant at the  Anal fissures are a well-known disease worldwide. In the United States, approximately 235,000 new cases of anal fissures are diagnosed each year, while in Italy it is the second most common cause of proctologist visits ,2. Anal Thus, treatment for anal fissures is aimed at reducing IAS spasms to relieve pain, decrease ischemia and promote the healing of ulcers. Acute anal fissures are commonly managed by conservative medical treatment, while chronic anal fissures are refractory to such treatment. Surgical treatment, such as sphincterotomy, is commonly required for the treatment of chronic anal fissures or abscesses, providing symptomatic relief ,7. HowevDue to such surgical complications, reversible relaxation of the IAS through botulinum toxin type A (BTX) injection has become a common treatment . The injConsecutive symptomatic adults with chronic anal fissure refractory to conventional endoscopic four-quadrant BTX injection were enrolled in the study. Refractory was defined by patient’s who failed prior medication and endoscopic botox treatment without the guidance of an endoscopic ultrasound. The inclusion criteria were as follows: (i) evidence of induration in the anal canal, (ii) persistent symptoms of post-defecation/nocturnal pain or bleeding for over 3 months, (iii) failed previous endoscopic injection. The exclusion criteria included: acute anal fissure, anal fissure secondary to underlying pathology, known sensitivity to BTX, or patients who were unable to consent to the procedure. The study protocol was approved by the Institutional Review Board. EUS was performed using a linear array echoendoscope . Eighty All patients were followed up at 1- and 2-month intervals by telephone or in person. The patients were asked to determine their pain level by using a 10-point visual analog pain scale. This was compared to the pain score at baseline. t-test. p-values of less than 0.05 were considered to be statistically significant. All statistical analyses were performed using Excel. All results were expressed as the mean +/− standard deviation, and differences between pre- and post-visual analogs were determined via a paired Twelve consecutive patients were assessed for eligibility; of these, four patients did not meet the inclusion criteria. Three patients were unable to consent or refused to consent to participate in the study, and one patient had an acute fissure (not chronic) and superimposed hemorrhoids.All patients reported severe post-defecation pain. All patients had evidence of a posterior anal fissure from a digital rectal exam and colonoscopy.p < 0.01 level. We offered EUS-guided BTX injections into the IAS to all patients who presented with anal fissure pain for over 3 months that had been refractory to prior endoscopic BTX treatments. A total of eight patients with prior flexible sigmoidoscopy with BTX injection were included in the study. The outcome was defined as excellent if there was a 50% or greater decrease in the visual analog pain score. Six patients had an excellent response to BTX at the two-month interval using the visual analog pain scale. One patient had a moderate response with a pain score reduction of 40%. One patient, on chronic narcotic treatment, had no response . Opioid Current therapies for anal fissure include pharmacotherapy, flexible sigmoidoscopy-guided BTX injection and surgical myotomy. In a prior study, Brisinda et al. compared a conservative treatment of 0.2% glyceryl trinitrate ointment to botulinum toxin in patients. This study revealed a 96% healing rate in the botulinum toxin group, compared with 60% in the glyceryl trinitrate group . Thus, mIn this pilot case series, we examined the utility of EUS-guided BTX injection into the IAS under direct visualization in patients with anal fissures refractory to medications and endoscopic therapies. Consecutive patients in our study who underwent EUS-guided BTX injection had excellent responses with a reduction in pain score with no complications. Furthermore, a statistically significant improvement in the visual analog scale was seen.While, to our knowledge, our study is the first case series to report on EUS-guided botulinum injection for refractory anal fissures, we recognize several limitations. First, patients’ inclusion and response assessment was based on some subjective criteria which are difficult to quantify and, therefore, might potentially introduce bias into our results. Second, the sample size was small, and thus our results may not be generalizable or applicable to larger populations. In addition, because our sample size was small, we cannot exclude the presence of selection bias in our study. Finally, the follow-up time was short and, therefore, no firm conclusions can be drawn from our results on long-term outcomes of this procedure and related complications. Furthermore, large multicenter studies will be needed to address these limitations.In summary, EUS-guided BTX injection is a promising technique for patients with anal fissure refractory to medical therapy and appears to be superior to endoscopic BTX injection without ultrasound guidance. More studies need to be conducted to confirm the efficacy of this approach.


Introduction: The main objective of this study is to validate the PIPP-R scale (Premature Infant Pain Profile-Revised) for measuring neonatal pain in the Spanish hospital setting. Materials and Methods: The original scale will be translated from English into Spanish and a consensus translation will be prepared by the research team, which will be back-translated from Spanish into English. The content validity of the Spanish version of the scale will be measured using the Delphi method. Subsequently, a multicenter observational study will be conducted to assess construct validity, internal consistency, and intra-observer and inter-observer agreement. Pain will be assessed by comparing scores for a specific non-painful procedure with those for a specific painful procedure. The sample will include 300 subjects in intensive care and intermediate care units, who will be equally distributed among the participating hospitals. The subjects will be stratified into three groups by gestational age. Discussion: The original version of the PIPP-R scale is useful for objectively assessing neonatal acute and procedural pain from a gestational age of 25 weeks and over. It is important to culturally adapt the original validated scale and to test its validity and reliability in the Spanish healthcare context. The results of this study may represent significant progress in pain management. In the neonatal stage, from birth to 28 days of life, pain is a complex biological, psychological, and social phenomenon. Valid, reliable assessment instruments are thus necessary given the multidimensional nature of pain, its individual, subjective nature, and the inability of neonates to verbally express the intensity of their pain.It has been established that neonatal patients are capable of perceiving pain in the same way as adults . HoweverPain assessment is the cornerstone of effective pain management. The American Academy of Pediatrics (AAP) position statement on neonatal pain  stipulatHowever, this is currently not uniformly implemented. A Europe-wide study led by the EUROPAIN Survey Working Group  concludeThere are multiple pain assessment scales for neonatal patients, which differ according to the type of pain assessed, the gestational age of the patient, and the characteristics of their items. However, currently, none of them has been validated and culturally adapted to the Spanish healthcare context. A systematic review published in 2019  providesPain in NBs can have multiple consequences. Some are immediate, such as stress and haemodynamic instability, and others are long-term, such as allodynia, peripheral sensitisation, reactivity to pain continuing after discharge, altered somatisation, and changes in the subcortical white matter of the brain ,7,8,9.A study conducted in France in 2005 and 2006 (EPIPPAIN) showed that painful procedures are very frequent in hospitalized NBs. For the 430 NBs included in the study, there was a mean of 17 painful procedures per day per sick NB, most of which were not accompanied by analgesia . SimilarThe author of the original Premature Infant Pain Profile (PIPP) scale, Dr Bonnie Stevens, proposed the scale because of a persistent clinical problem that she had identified: inadequate measurement of neonatal pain in preterm newborns (PTNBs) . She subNeonatal patients are unable to express painful sensations verbally. As a result, they are completely dependent on the subjective judgement of their care team for the interpretation and management of their pain.Ensuring an optimal level of comfort and reduced stress using pharmacological and non-pharmacological measures is a major challenge for neonatal unit workers. Adequate pain assessment is necessary for the correct implementation of these measures.Pain assessments should be determined by the multidisciplinary team caring for neonates . Scales The availability of a neonatal pain scale (such as the PIPP-R) that has been validated and culturally adapted to the Spanish healthcare context is crucial for the provision of high-quality care to neonatal patients at an optimal level of comfort.The PIPP-R scale was chosen because it fits the characteristics of hospitalized neonatal patients in Spain, because its original English version has been demonstrated to be valid and reliable, and because it is the most widely used scale ,14.For all these reasons, and in view of the lack of a validated scale for neonatal pain assessment in hospital settings in Spain, we deem it necessary to validate the PIPP-R scale cross-culturally. This re-validation is necessary when changing the language of the original scale, as the reliability and validity of the new version must be ascertained for use in the new language population. In addition, the use of validated scales as data collection instruments in research studies improves methodological precision and facilitates comparisons with similar studies.To culturally adapt the scale and its instructions for use in the Spanish healthcare context.To explore the validity of this adaptation.To measure its reliability.The primary objective of this study is to culturally adapt and validate the PIPP-R scale for use in the Spanish healthcare context by addressing the following research objectives: This is a prospective, observational, multicenter study. The recommendations of the SPIRIT Statement were followed when developing this protocol .In the first phase, the aim was to produce a cultural adaptation, i.e., an equivalent translation not only of the words, but also of the concepts and technical criteria found in the questionnaire . The aimConsent was sought from the author of the original scale for its cross-cultural adaptation and validation into Spanish. Once permission was obtained, an independent pairwise translation was performed: the original scale and its instructions for use were translated into Spanish by a bilingual native Spanish-speaking healthcare professional and a bilingual native Spanish-speaking non-healthcare professional. Subsequently, both translators agreed on the first Spanish version. This first version was back-translated into the source language/context by a bilingual native English-speaking healthcare professional and a bilingual native English-speaking non-healthcare professional independently. A second English version was produced based on the consensus of both translators on their respective back-translations, which was then compared with the original English scale by the research team for similarity/equivalence, producing the final English version of the back-translated scale.In the second phase, to ensure that the items represent the phenomenon to be measured, content validation was carried out through evaluation by a group of experts.A heterogeneous group of 10 experts in the fields of pain and neonatal care, with different professions, levels of training and experience, and from a variety of locations was selected according to adapted translation of Quatrini’s criteria for expertise based on the literature  Table 2Table 2. ® platform. This platform was also used to assess the experts’ suggestions via the Delphi method, giving them the opportunity to leave their opinions/suggestions for each item for potential modification.The characteristics relating to the relevance, ambiguity, clarity, and simplicity of the items on the scale were rated from 1 to 4 using an ad-hoc online survey on the LimeSurveyThe Content Validity Index (CVI) was used to calculate this in accordance with Lynn and Yahgmale ,19.To assess the results, the CVI of each item (I-CVI) and the CVI of the scale as a whole (S-CVI) were estimated as per Polit and Beck . The I-CIn keeping with the Delphi method, the initial survey, containing closed and open questions, was sent to the experts. An initial analysis of their answers was performed by the research team and items were modified as appropriate. Subsequently, the questionnaire was sent out for a second time with the modifications and the results of the first assessment, highlighting the conclusions of all experts. After their responses were received, a further analysis was carried out and a final report was produced and sent to all participating experts.In the third phase, a prospective, observational, multicenter study will be conducted in hospitals in the Spanish National Health System. These will be level II and III hospitals according to the classification of the Spanish Society of Neonatology (SENeo). The study will begin in September 2022 and will end when the sample is complete.At the same time, the scale will be assessed for feasibility with the nurses collaborating in the multicenter study.The study setting will be the neonatal units at the Spanish Health System hospitals classified as level II and III according to the SENeo , whose pIntermediate or Basic Neonatal Care: care of NBs of gestational age above 32 weeks or weighing more than 1500 grams with a mild condition requiring special intermediate care techniques.Neonatal Intensive Care: care of NBs with a life-threatening medical/surgical condition requiring special treatment and care on a continuous basis.These hospitalization units are divided into Intensive Care and Intermediate or Basic Care, defined in the Spanish Royal Decree 1277/2003 of 10 October as follows: The following hospitals have so far agreed to participate: 12 de Octubre University Hospital in Madrid, University Hospital Complex in A Coruña, Donostia University Hospital, La Fe University and Polytechnic Hospital in Valencia, Clinical University Hospital in Valencia, Santa Lucía General University Hospital in Cartagena, Río Ortega University Hospital in Valladolid, and Lozano Blesa Clinical Hospital in Zaragoza. We are still awaiting confirmation from other hospitals.The study participants will be neonatal patients hospitalized in several of the aforementioned units from the start of the study until the sample is complete.The inclusion criteria for participants will be: (a) PTNBs older than 25 weeks gestational age at birth; (b) receiving a painful procedure for diagnostic, therapeutic, or care purposes; (c) receiving a non-painful procedure within 24 h of the painful procedure; (d) parental consent; (e) haemodynamically stable neonates. Patients receiving analgesia can participate, but this will be taken into consideration at a later stage.Patients will be recruited as they meet the inclusion criteria and once a member of the research team has informed their parents about the study, given them the information sheet and informed consent form, and one of the parents has returned the informed consent form with their signature.The exclusion criterion will be (a) patients being treated with muscle relaxants that may interfere with pain responses.A variety of methods are used to calculate the necessary sample size in scale validation studies, and many of the studies consulted do not report on the criteria used to do so. The samples in these studies range from 30 to 100 subjects.To calculate the sample size, Streiner  suggestsAfter discussion, the research team decided to select 300 subjects divided into 100 subjects per group, as recommended by several authors , who proThe number of subjects from each participating hospital will be calculated based on the number of admissions in the preceding year.The neonates included in the study will be divided into three homogeneous groups for analysis based on their corrected gestational age, which is to be calculated in weeks and days of postmenstrual gestational age plus weeks and days of life.Very and extremely premature infant: 25–31 + 6 weeks gestational age.Moderately premature infant: 32–36 + 6 weeks gestational age.Term infant: >37 weeks gestational age.The PIPP-R scale for the assessment of neonatal acute and procedural pain  consistsConstruct validity: difference between the total pain scores for the painful procedure and for the non-painful procedure as measured using the Spanish version of the PIPP-R.Inter-observer and intra-observer validity: difference between the total score given by the collaborating nurse and the total score given by a member of the research team.Sociodemographic and clinical variables: birth weight, gestational age, sex, diagnosis on admission, admitted to the NICU or to intermediate or basic care, and days of life at the time of measurement.Variables related to pain prevention: use of sucrose, breastfeeding or expressed breast milk, restraints, non-nutritive sucking, and/or pharmacological analgesia. All pharmacological analgesia administered two hours before the procedure shall be documented, including whether it is intermittently or continuously administered and the specific drug used. Variables related to painful procedures: the heel prick test, venepuncture, or dressing removal ,24.Variables related to non-painful procedures: Change of position or nappy change. It shall be documented whether the procedure has been carried out by the professionals in charge of the patient or by the parents.Variables related to the nurse observer: years of experience in neonatal care, sex, age, and work unit.® electronic data collection notebook, which will be pilot-tested by the research team and collaborators for content validation purposes.All variable data will be collected in the REDCapData collection will begin once the nurses have completed their standardized training in the use of the PIPP-R scale and the data collection notebook . This trWhenever a collaborating nurse identifies a painful or non-painful procedure scheduled for a patient, she will contact her facility’s expert assessor to arrange the timing of the pain assessment and seek parental consent.The nurse and the study facility coordinator will independently measure pain in real time at the bedside for a painful procedure and for a non-painful procedure on the same patient within 24 h of one another. Under no circumstances will a procedure be purposefully performed on a patient in order to conduct the study.Observe infant for 15 s at rest (without manipulation) and assess vital sign indicators (highest heart rate and lowest oxygen saturation) and baseline behavioral state.Observe infant for 30 s after procedure and assess change in vital sign indicators and duration of facial actions observed.If the sub-total is >0, score for corrected gestational age and baseline behavioral state and calculate the total score by adding all sub-scores.To measure pain, the patient’s heart rate and oxygen saturation must be monitored using continuous electrocardiography and pulse oximetry respectively. This will be necessary to assess the patient, as per the PIPP-R, before and during the procedure to be measured. Measuring pain with the PIPP-R scale involves the following steps:In addition, the electronic data collection notebook includes data on the collaborating nurse, the patient, and the procedure described earlier in this protocol.Intra-observer reliability will be measured at a single facility due to the need for the necessary resources to be in place. Recording is vital, as intra-observer reliability must be measured by a single individual comparing pain assessment at the bedside with the pain assessment for the same procedure after a minimum period of two weeks. The patient’s face and vital signs will be recorded during the painful and non-painful procedures at their bedside in the neonatology department. Two Samsung Galaxy cameras will be used for this purpose, and the recordings will be transferred to a dedicated computer in the study room in the neonatology department at 12 de Octubre University Hospital in Madrid, Spain.The patient timeline is shown in The descriptive analysis of quantitative variables will be carried out using means and standard deviations, as well as 95% confidence intervals, or medians and interquartile ranges if the sample is not normally distributed. Qualitative variables will be expressed as frequencies and percentages.Construct validity, understood as the success of the instrument in representing and measuring the theoretical concept in question, will be explored using exploratory factor analysis (EFA). Values between 0.5 and 0.7 will be considered significant; values greater than 0.7 will be considered relevant .Internal consistency, which measures the homogeneity of the items, will be assessed using Cronbach’s alpha coefficient. A low Cronbach’s alpha (α  <  0.70) indicates inadequate internal consistency, whereas a high Cronbach’s alpha (α  >  0.90) suggests redundancy of items .Inter-observer reliability, i.e., the level of agreement between different observers of the painful procedure and the non-painful procedure, will be measured using the intraclass correlation coefficient (ICC). Values > 0.75 indicate excellent levels of reliability ,27.Intra-observer reliability, referring to a single observer’s level of agreement between assessments of the painful procedure and the non-painful procedure after a period of time, will also be measured using the ICC. Values > 0.75 indicate excellent levels of reliability ,27.The feasibility of the scale will be measured by surveying the nurses collaborating in the study using the same survey employed by the author of the original PIPP-R scale validated for the same purpose .p < 0.05. Data analyses will be performed using SPSS Statistics v. 25 software .The statistical significance threshold for all analyses will be set at Prior to the study, parents and/or guardians of the neonates who are eligible to participate will be informed of the study objectives and invited to sign the informed consent form.Confidentiality will be ensured. Participants will be assigned a unique identification code that will be used throughout the study to preserve their anonymity.Only techniques that are needed for the neonates’ health will be performed and assessed , and they will not be influenced by the conduct of this study.The project was approved by the Ethics Committee for Research with medicinal products (ECRmp) for 12 de Octubre University Hospital (19/271) and by the Research Ethics Committee for Rey Juan Carlos University in Madrid (2406201911219).The research team undertakes to conduct the study in accordance with current Spanish regulations, best clinical practice, and the ethical principles for medical research in humans set out in the Declaration of Helsinki.The validation study of the original PIPP-R scale in English  revealedTherefore, we believe it is important to the original validated scale and to test its validity and reliability in the Spanish healthcare context. This is the rationale underpinning the study, which will be carried out using a sample of a large, heterogeneous population  with a range of health conditions.The results of this study may represent significant progress in pain management  as well Potential limitations of the study include failing to reach the estimated necessary sample size, in which case we will consider the need to include new hospitals fulfilling the study requirements.Other limitations may be linked to training participants to use the scale, as the SARS-CoV-2 pandemic may preclude face-to-face training, or to a lack of funding, which is why intra-observer reliability will only be assessed at the patients’ primary hospitals.We believe that the results of this study will prove highly relevant for the provision of comprehensive care to neonatal patients by healthcare professionals working in neonatal units, as well as for healthcare institutions.The cross-cultural validation of a pain measurement scale for neonatal patients in the Spanish healthcare context will improve pain management in neonatal patients by optimizing the use of sedation and analgesia according to the patient’s current clinical status at all times. It will also improve the cost-effectiveness of nursing care by taking into consideration patients’ pharmacological and non-pharmacological requirements, as well as enhancing the quality of nursing care itself, as the professionals caring for these patients will possess in-depth knowledge of the tool.Furthermore, potential sequelae could also be prevented with proper assessment and management of pain, reducing its impact on both the individual and the healthcare system as a whole.


To assess the prevalence, incidence, location, and behavior of chronic pre- and postoperative pain in bariatric surgery, and the use of analgesics.A cross-sectional e-survey was conducted on 3928 post-bariatric patients and four-time points for pain assessment were evaluated: preoperative, on the ward, day 1 at home postoperatively, and present time (at the time of the e-survey). A numerical rating scale (NRS) was used to assess the level of pain (0 to 10). The general incidence of chronic pain was calculated, as also, subgroups were defined as group A (pre and postoperative chronic pain), B , and C . Besides the pain intensity, location of pain, and the use of analgesics were investigated.p < 0.001). The ORs for present postoperative chronic pain were OR 1.45, 1.7, and 1.71  compared to respectively preoperative chronic pain, pain at the ward, and pain at day 1 after surgery. Among all participants, 4.6% consumed chronic analgesics. Of these, paracetamol was used most frequently (3.8%), followed by tramadol (1.3%) and oxycodone (0.5%).A total of 3279 patients (83.9%) responded to the survey. Preoperative and postoperative chronic pain was found in 343 (10.5%) and 264 (8.1%) patients, respectively. In group A, chronic pain was present in 4.8% of the patients; in group B, it was present in 5.7%; and in group C in 3.3% of the patients. Furthermore, in 4.5% of patients pain was located in the abdomen, which was higher as compared to before surgery (+ 2.3%, In this e-survey, chronic postoperative abdominal pain was prominent in patients after bariatric surgery. Of patients, 3.3% that were without preoperative chronic pain developed chronic pain after surgery. Opioid consumption in the queried population was relatively low.The online version contains supplementary material available at 10.1007/s11695-022-06354-9. Currently, more than 650 million 13%) adults suffer from obesity, which is defined as a body mass index (BMI) of 30 kg/m3% adultsAcute post-surgical pain occurs in the first 1 to 3 months after surgery. The duration and intensity of post-surgical pain varies with the type and duration of surgery, patient factors such as gender, race, age, and surgical complications , 5. In 2Postoperative pain is commonly treated according to a multimodal approach that includes paracetamol, non-steroidal anti-inflammatory drugs, and opioids. Opioids bind in plasma to the transporter protein alpha-1-acid glycoprotein. The concentration of this protein is usually higher in patients with a chronic inflammatory state such as obesity. As a consequence, the free fraction of the opioid is expected to be lower and as a consequence a reduced analgesic effect of opioids; patients with obesity likely need higher dosages to achieve similar effects .For a better understanding of perioperative pain in patients undergoing obesity surgery, knowledge of the prevalence, type of pain, and duration of pain, research is necessary. To our knowledge, this is not yet investigated/studied. Therefore, in this study, we conducted a cross-sectional e-survey for the prevalence and location of chronic pre- and postoperative pain, the incidence of new or disappeared chronic postoperative pain in bariatric surgery, and medication use.A cross-sectional e-survey was conducted between August 2017 and January 2019 at the Dutch Obesity Clinic west, The Hague, the Netherlands. To assess the prevalence and incidence of chronic pre- and postoperative pain in patients undergoing bariatric surgery. Written consent was obtained from all the patients. The data were analyzed anonymously. The study was conducted in accordance with the principles of the Declaration of Helsinki and was approved by the local ethical committee of the Dutch Obesity Clinic medical research institute before the e-survey was sent.The prevalence and location of chronic pre- and postoperative pain, the incidence of new chronic postoperative pain, and the use of medication after bariatric surgery.All patients in this survey met the inclusion criteria prior to surgery. Therefore, all the patients were preoperatively screened and indicated for bariatric surgery according to the International Federation for the Surgery of Obesity and Metabolic Disorders (IFSO) criteria. They were selected from hospital electronic databases on primary sleeve gastrectomy or RYGB procedures and contacted regarding participation in this survey. All patients who denied participation were excluded from the study.The questionnaire was sent at least three months after the surgery was performed. The baseline characteristics of the patients included pre- and postoperative body mass index (BMI); the weight was measured before surgery at the clinic and after surgery by the patient itself.The pain was assessed at four different time points: preoperative, at the ward, 1 day after surgery at home, and at the time of the e-survey assessment. A numerical rating scale (NRS) was used to assess pain intensity on a scale of 0 to 10 with zero indicating no pain and 10 being the most pain imaginable. Besides the pain localization, the intake of analgesics was also evaluated.A: Patients who had preoperative pain and continuing postoperativeB: Patients who had preoperative chronic pain but are no longer postoperative.C: Patients without preoperative chronic pain but suffering from chronic pain postoperative.Chronic pain was defined as pain during at least three months intermittently present in daily life. Besides the general incidence of chronic pain, this study also defined three subgroups of patients.https://www.castoredc.com) and handled according to Good Clinical Practice guidelines, Data Protection Directive certificate, and complies with Title 21 CFR Part 11. Furthermore, the data center where all the research data was stored was ISO27001, ISO9001 certified, and Dutch NEN7510 certified.The analysis was performed on a blinded data set after the medical/scientific review was completed and all protocol violations were identified and solved, and the data set was declared complete. All data and survey questionnaires Appendix  were colQ-Q plot, and Levene’s test. Categorical variables were expressed as n (%). Continuous normally distributed variables were represented by their mean and standard deviation, discrete by their median and interquartile range for skewed distributions. To compare categorical variables among different groups, the Pearson’s Chi-square test or Fisher’s exact test was used, when appropriate, and in case of paired groups by the McNemar test. Normally distributed continuous data were tested with the independent samples, and Student’s t-test was used to compare continuous variables between independent samples and, in the case of skewed data, the Mann–Whitney U-test was used. The correlation between the NRS scores in different phases was determined using a Pearson product-moment correlation coefficient for normally distributed data or Spearman’s rank correlation coefficient for non-normally distributed data. Logistic regression was used to determine the odds ratio of developing chronic pain. P-values of < 0.05 were considered statistically significant. Statistical analyses were performed using R (version 4.0.4) packages.We used descriptive statistics and inferential statistics. All data were first tested for normality by a Kolmogorov–Smirnov test, a n = 3279). Sleeve gastrectomy (LSG) and Roux-en-Y gastric bypass (RYGB) surgeries were performed in 16.9% and 83.1% of patients, respectively. Age at the time of the survey was 49 ± 11 years. In our cohort, 82.5% of patients were female and 17.5% were male. The mean time between surgery and the e-survey was 3.4 ± 1.6 years. Surgery periods were between 2009 and 2018.A total of 3928 patients were approached between August 2017 and January 2019. From these, 83.9% responded with informed consent to participate in the study  was 68.3 ± 24.7%,and % total weight loss (%TWL) was 31.8 ± 10.4  of patients with a NRS of 6.9 ± 1.6. Preoperatively, the pain occurred in the back, knee, pelvis/buttocks/thighs, lower legs/feet, and abdomen in 213 (6.5%), 213 (6.5%), 121 (3.7%), 151 (4.6%), 73 (2.2%) patients, respectively (Table Preoperative chronic pain was noted in 10.5% (p = 0.118).There were no significant differences between LSG and RYGB procedure selection and the incidence of preoperative chronic pain (p = 0.067), but the patients with an LSG procedure had significantly higher NRS scores (NRS 7.18 ± 1.97 vs. 6.57 ± 1.82) (p = 0.0004).After surgery on the ward, 799 (24.4%) of patients experienced acute pain with a NRS of 6.6 ± 1.86. There were no significant differences between LSG and RYGB procedures in the presence of pain at the ward (p = 0.148) or NRS scores (p = 0.776).Postoperative, 1 day after surgery, 779 (23.8%) patients experienced acute pain with a NRS of 5.7 ± 1.9. There were no significant differences between LSG and RYGB procedures in the presence of pain at home (n = 264) with a NRS of 5.9 ± 1.9.Postoperative pain had an incidence of 8.1% (p < 0.001)), pelvis/buttocks/thighs  (p < 0.001)), knee ), lower legs/feet  (p < 0.001)), and abdomen ), respectively  (p = 0.431).There were no significant differences between LSG and RYGB procedures in the presence of postoperative chronic pain (Group A: pain was present in 4.8% of patients. (156 out of 3279 patients)Group B; pain was present in 5.7% of patients. (186 out of 3279 patients)Group C; pain was present in 3.3% of patients. (108 out of 3279 patients) (Table p = 0.873).All three groups were not significantly different in patient characteristics (p = 0.002), with a significant coefficient of determination (COD) on the NRS score of R2 13% (p = 0.003).The odds for the development of postoperative chronic pain as compared to preoperative chronic pain was OR 1.45 (CI95% 1.2–1.69) (p = 0.003), with a significant COD on the NRS score of R2 6% (p = 0.001).The odds for the development of postoperative chronic pain compared to the presence of pain at the ward was OR 1.70 (CI95% 1.46–1.94) (p = 0.0048), with a significant COD on the NRS score of R2 17% (p = 0.0024).Finally, the odds for the development of postoperative chronic pain as compared to the presence of pain at home was OR 1.71 (CI95% 1.47–1.95) , followed by tramadol (1.3%), oxycodone (0.5%), diclofenac (0.4%), naproxen (0.3%), ibuprofen (0.2%), amitriptyline (0.2%), paroxetine (0.2%), citalopram (0.2%), diazepam (0.2%), morphine (0.1%), fentanyl (0.1%), and pregabalin (0.1%).In this study, a cross-sectional e-survey was performed in 3279 patients after bariatric surgery. The preoperative prevalence and the postoperative incidence of pain were 10.5% and 8.1%, respectively. Sub-group analysis of chronic pain revealed that, in group A, pain persisted in 4.8% of patients, in group B (5.7%), pain was present preoperative but no longer after the bariatric operation, and in group C (3.3%), new pain started after the operation.Chronic postoperative pain is associated with decreased quality of life, sleep and mood disorders, and neuropathic symptoms . Additio2, EWL 68.3%) leading to a reduction in chronic pain by 5.7% (group B), with predominantly a reduction of musculoskeletal pain in the back, pelvis, knees, and lower legs/feet. This was not unexpected as bariatric surgery–induced weight loss has been earlier shown to significantly improve musculoskeletal pain [In our study, after bariatric surgery, BMI decreased over time . In this study, these patients experienced chronic pain preoperatively and retained this pain after the operation (group A). Group B in this study also had preoperative chronic pain, but this pain was not present anymore after surgery. There were no significant differences between the patient's characteristics between groups A and B, so therefore, predicting what patients will have postoperative (chronic) pain remains unanswered, but this is an important field for future research.Our study found an increased OR in the development of postoperative chronic pain; this highlights the importance and attention to pain treatment during the preoperative screening, hospital admission, and discharge phase. First, our study found that when preoperative chronic pain is present, this is correlated with postoperative chronic pain . Therefore, it is important that before discharge, proper pain medication and instructions for the follow-up phase are in place.Furthermore, 2.2% of the patients in our survey had preoperative chronic abdominal pain. We observed a twofold increase in abdominal pain postoperatively, which is in accordance with previous reports , 17–20. There are several speculations regarding the etiology of chronic abdominal pain after bariatric surgery: (1) behavioral and dietary disorders such as over and rapid eating resulting in mechanical distension of the pouch or reduced stomach; (2) functional disorders such as constipation, diarrhea, irritable bowel syndrome, and dumping syndrome; (3) biliary disorders such as cholelithiasis, choledocholithiasis, or sphincter of Oddi dysfunction; (4) pouch or remaining stomach disorders such as peptic ulcer disease, gastro-gastric fistula, gastroesophageal reflux disease (GERD), hiatus hernia, and internal hernias; and finally (5) disorders in the abdominal wall like anterior cutaneous nerve entrapment syndrome (ACNES) , 22–24. n = 933) of bariatric patients were chronic opioid users. Of this group, 77% continued using chronic opioids the year after surgery. On average daily use of 45.0 mg morphine equivalents preoperative and 51.9 mg daily postoperative (p < 0.001), there was an increase in opioid consumption after the bariatric surgery. Furthermore, the change in morphine equivalents before versus after surgery did not differ between individuals who lost more than 50% excess weight loss vs. those with 50% or less [The US Center for Disease Control reported an increase in opioid use in patients with persistent pain after bariatric surgery . In a su or less .Another study testing the effect of new persistent opioid use on physiologic and psychologic outcomes following bariatric surgery found a new persistent opioid use of 6.3% . In this study, the excess body weight after 1 year of bariatric surgery was less, compared to the group without new persistent use. Also, new persistent opioid use had significantly worse psychological well-being, body image, and depression score .In contrast to the US data, we detected that chronic analgesics were consumed by a low proportion of patients , with opioid consumption much lower than reported in US studies , 27. IrrThis study showed that treatment with bariatric metabolic surgery has positive and negative effects on the presence of pain in a patient with obesity. Our study presented an overview of the incidence and correlations of pain, but questions remain unanswered on the characteristics of the patients prone to develop chronic pain.The call to action should focus on research on the causes and effects of pain in patients with obesity in the pre-peri- and postoperative phases of surgery.This e-survey also had some limitations. We performed a retrospective survey without retrieving data from an electronic or paper hospital database, whereby possible more variables could have been scored. Therefore, checking for bias and correcting for confounding factors was not possible. Furthermore, recall bias may be present in this survey. We requested to report on pain scores for a relatively long period after surgery, and since pain scoring then relies on the retrieval from memory, such scores become unreliable. This may have led to over- or underestimation of pain scores . Still, our survey also detected a proportion of patients with present pain, which evidently is a more reliable estimation. Also, we did not gather information on the preoperative drug dosage and, therefore, the changes in the analgesic usage, which would be informative to link to pain perception and development. This must be performed in future studies.We observed that postoperative pain, particularly abdominal pain, may persist in a subset of patients undergoing bariatric surgery. In patients with pain prior to surgery, especially joint pain diminished postoperatively. New incidences of chronic pain were observed in patients with no history of any pain prior to their bariatric surgery. We contend that there is a need to achieve a consensus regarding postoperative pain management in patients after bariatric surgery.Supplementary file1 (136 KB)Below is the link to the electronic supplementary material.


Attentional deficits in patients with chronic pain are common and well studied. Yet, few studies have examined the effects of chronic pain on more complex cognitive abilities that rely on well‐functioning attentional systems. With the current study, we aimed to investigate whether the impact of chronic pain on attention affects creative ideation as measured with an adaptation of the alternate uses task (AUT).Performance in the AUT was compared between 33 patients suffering from chronic pain and 33 healthy matched controls. While solving the task, EEG was recorded to measure the degree of internally directed attention assessed by means of task‐related power (TRP) changes.The results revealed that patients with chronic pain generated less creative ideas than healthy controls. This lack of performance was accompanied by lower event‐related synchronization (ERS), especially in right parietal sites. Furthermore, these ERS differences explained one‐third of the inter‐group variance in AUT performance.These results suggest that performance decrements in creative ideation in patients with chronic pain may be at least partly attributable to attentional impairments associated with chronic pain.Chronic pain negatively affects attention and more complex cognitive abilities. However, the underlying psychophysiological mechanisms and the role of attention as a source of these impairments in more complex abilities are poorly understood. By analyzing task‐related power changes in the EEG, the role of internal attention in creative ideation could be determined, revealing the functional relationship between chronic pain, attention, and a more complex cognitive ability. Regarding educational level, two patients (6%) finished mandatory school, 22 (67%) finished an apprenticeship and 9 (27%) finished high school or higher education. Twenty‐nine patients (88%) reported being right‐handed. Patients were recruited at a Swiss tertiary psychosomatic university clinic and had been diagnosed with chronic pain disorders according to ICD‐10 . Most patients had musculoskeletal pain (76%), followed by chronic headache (12%). Six percent of the patients did not give any information on the localization of their pain. For study inclusion, patients with chronic pain were required to speak German fluently and have a negative history of dementia, psychosis, brain concussion, neurological diseases, alcohol‐related disorder and intake of medications such as antihistamines, benzodiazepines or opioids. Medication intake was recorded by a physician. While four (12%) patients were prescribed concomitant antidepressants and anticonvulsants, thirteen (39%) patients were prescribed only antidepressants and two (6%) patients only anticonvulsants. Eleven (33%) patients were not taking any medication with a potentially sedating side effect. Twelve (36%) patients reported a pain duration from at least 1 to 5 years, six (18%) patients from 6 to 10 years and 15 (45%) patients more than 10 years.The sample of patients with chronic pain consisted of 43 participants. Of these, four patients were excluded because they misunderstood the AUT, four were excluded because of poor EEG signal quality and two were excluded because they were identified as outliers . The final sample consisted of 33 patientsM = 42.7, SD = 14.3) were recruited through  media advertisements and personal contacts. Twenty‐two (67%) of the participants finished an apprenticeship, and 11 (33%) finished high school or higher education. Twenty‐six (79%) of the participants reported being right‐handed. Inclusion and exclusion criteria were the same as for patients with chronic pain. Healthy participants were recruited to match the patients' gender, age, educational level, and handedness.As a control group, 33 healthy participants  ranging in age from 20 to 64 years .2.2Actual and average pain intensity was measured on a visual analogue scale  independently evaluated the creativity of the ideas. Items were rated by each rater in turn. For this purpose, all responses per item were listed in a separate Excel sheet. Responses were sorted alphabetically to facilitate how often multiple participants generated the same idea. In the first step, raters were supposed to check whether the idea met the criterion of usefulness/effectiveness , and in the second step, raters were supposed to consider the uniqueness/originality of the idea. Raters were then instructed to give one rating per response. Thus, the ratings were based on the effectiveness as well as the uniqueness/originality of the response, which are the two essential criteria for a creative idea  and the corresponding DSI‐STREAMER recording software. EEG was synchronized with the AUT automatically by sending triggers from the presentation computer to the EEG recording software during the EEG recording. According to the international 10–20 system, 21 electrodes  were arranged. In addition, an electrooculogram (EOG) was installed to measure eye movements. For this purpose, two horizontal electrodes were placed to the left and right of the eyes , while Fp2 and an electrode on the infraorbital ridge of the right eye were used to measure vertical EOG. During recording, Pz served as a reference electrode, which was re‐referenced to electrodes on the earlobes (A1 + A2) via DSI‐STREAMER recording software before exporting the data.EEG and EOG were recorded at a rate of 300 Hz and resampled to 256 Hz using the software BrainVision Analyser 2.2. The continuous signal was further filtered offline (0.1–30 Hz). With Gratton and Coles’  ocular ci, reference) from log‐transformed power during the creative ideation interval  according to the formula: TRP = log − log  for the difference in AUT scores between patients with chronic pain and healthy controls. Provided with an α error probability of α = 0.05 and statistical power of 1 − β = 0.85, the software G*Power  were conducted using the statistical software RStudio version 1.4.1103. To test for differences in AUT scores between patients with chronic pain and healthy controls, a one‐way analysis of variance (ANOVA) with the between‐subjects factor ‘Group’ (patients vs. controls) and the dependent variable AUT score was conducted. For the analysis of TRP, a three‐way mixed‐model ANOVA was computed with one between‐subjects factor ‘Group’ (patients vs. controls), one within‐subjects factor ‘Position’ (eight electrode positions in each hemisphere) and one within‐subjects factor ‘Hemisphere’ (left vs. right). Post‐hoc pairwise comparisons were performed using Bonferroni‐Holm correction. Potentially significant TRP differences between patients with chronic pain and healthy controls were included as covariates in an ANCOVA with Group as the independent variable and AUT score as the dependent variable to test the impact of TRP differences on potential AUT differences between patients with chronic pain and healthy controls. Anxiety, depression and sleep duration were also considered potential covariates to rule out that the effects found were attributable to these potential confounding variables. To compare the effect of Group between ANOVA and ANCOVA, partial Furthermore, ANOVAs or correlation analyses were used to examine how the influence of antidepressants and pain intensity affected AUT scores and TRP values within the group of patients with chronic pain.Before conducting the ANOVAs, several assumptions regarding the absence of outliers, normality, homogeneity of variance and sphericity were checked  = 6.369, p = 0.014, ηp2 = 0.091. AUT scores of patients with chronic pain were significantly lower  than the AUT scores of healthy controls . Although both groups had an average score between ordinary ideas and creative ideas, the average responses of patients with chronic pain were significantly closer to the anchor of ordinary ideas (i.e. ‘2’) than healthy controls' responses. As can be taken from Table The one‐way ANOVA on the AUT scores of patients with chronic pain and healthy controls yielded a significant main effect Group, M = 2.029, SD = 0.27) than AUT scores of patients not taking antidepressants , these scores did not differ significantly, F = 3.212, p = 0.083, ηp2 = 0.094. However, it should be noted that there was probably not enough statistical power to find a significant effect due to the small sample size. Since it can be assumed that patients suffering from more severe pain are more likely to take antidepressants, we additionally considered the results with acute pain scores as a covariate. When considering pain severity as a covariate, the difference in AUT between patients taking antidepressants and patients not taking antidepressants was further reduced, F = 1.625, p = 0.212, ηp2 = 0.051, while pain severity was a significant predictor of AUT scores, F = 12.778, p = 0.001, ηp2 = 0.229. This covariation of antidepressants and acute pain suggests that the present study is not suitable for systematically investigating the influence of antidepressants.In patients with chronic pain, actual and average pain scores were significantly negatively related to AUT scores with moderate to strong effect sizes  = 2.337, p = 0.131, ηp2 = 0.035, of Position, F = 0.671, p = 0.609, ηp2 = 0.010 and Hemisphere, F = 2.740, p = 0.103, ηp2 = 0.041, and no significant two‐way interaction Group × Hemisphere, F = 0.099, p = 0.754, ηp2 = 0.002. However, there were significant two‐way interactions Group × Position, F = 3.880, p = 0.005, ηp2 = 0.057, as well as “Position” × “Hemisphere”, F = 3.133, p = 0.008, ηp2 = 0.047. Furthermore, the three‐way interaction Group × Position × Hemisphere was statistically significant, F = 2.274, p = 0.045, ηp2 = 0.034, which is depicted in Panel A of Figure Differences in TRP scores during creative ideation between patients with chronic pain and healthy controls were examined by means of a 2 (Group) × 8 (Position) × 2 (Hemisphere) mixed ANOVA with TRP values as the dependent variable. ANOVA yielded no main effect Group, F = 2.109, p = 0.151, ηp2 = 0.032, and Position, F = 1.290, p = 0.271, ηp2 = 0.020, nor the two‐way interaction Group × Position, F = 1.653, p = 0.153, ηp2 = 0.025, reached statistical significance. For the right hemisphere, the main effects Group, F = 1.843, p = 0.179, ηp2 = 0.028, and Position, F = 1.497, p = 0.203, ηp2 = 0.023, were also not significant. However, there was a significant two‐way interaction Group × Position, F = 4.988, p < 0.001, ηp2 = 0.072, in the right hemisphere. Bonferroni‐Holm corrected post‐hoc t tests for group mean differences yielded statistical significance at the parietal electrode sites P4, t(64) = −2.781, p = 0.007, Cohen's d = −0.685, and P8, t(64) = −3.102, p = 0.003, Cohen's d = −0.764  and in P8  than healthy controls, who showed the expected alpha power increases  = −2.300, p = 0.025, Cohen's d = −0.566, this was no longer significant after Bonferroni‐Holm alpha adjustment, α = 0.008 (0.05/6). For all other electrode sites, the differences between patients and healthy controls were not significant, all ts ≤ 1.659, ps ≥ 0.102, Cohen's ds ≤ 0.408.To better understand the three‐way interaction, we considered the right and left hemispheres separately. In the left hemisphere, neither the main effects Group, r = −0.291, p = 0.018, and depression scores, r = −0.245, p = 0.047, but not with sleep duration, r = 0.079, p = 0.530, anxiety and depression were considered as covariates. When taking anxiety into account as a covariate, the effect of Group remained a significant predictor of TRP values, F = 5.444, p = 0.023, ηp2 = 0.080, while the effect of anxiety did not reach statistical significance, F = 1.303, p = 0.258, ηp2 = 0.020. When taking depression into account as a covariate, Group further remained a significant predictor of TRP values, F = 5.930, p = 0.018, ηp2 = 0.086, while the covariate depression did not reach statistical significance, F = 0.093, p = 0.761, ηp2 = 0.001.TRP values at P4 and P8, where patients and healthy controls significantly differed, were averaged for each participant for further analyses. These TRP values were then correlated with anxiety, depression and sleep duration to examine the influence of possible covariates. As results revealed that there were significant relations of TRP values with anxiety, r = −0.058, p = 0.749, and between TRP values and average pain, r = 0.002, p = 0.991. Moreover, TRP values of patients taking antidepressants  and patients not taking antidepressants  did not significantly differ, F = 0.411, p = 0.526, ηp2 = 0.013.We further examined the averaged TRP values in relation to pain severity and antidepressants within the group of patients with chronic pain. Results revealed no significant relation between TRP values and acute pain, r = 0.257, p = 0.037, we considered it as a covariate in the one‐way ANOVA on AUT differences between patients with chronic pain and healthy controls calculated in the first step. The resulting ANCOVA revealed that the difference in AUT scores between patients with chronic pain and healthy controls was no longer significant when controlled for mean parietal TRP values, F = 3.463, p = 0.067, ηp2 = 0.052. The effect of the covariate mean parietal TRP value did not reach statistical significance as well, F = 1.738, p = 0.192, ηp2 = 0.027. Effect size ηp2 of the main effect “Group” decreased from ηp2 = 0.091 in the ANOVA to ηp2 = 0.052 in the ANCOVA, suggesting that about one‐third of the inter‐group variance in the AUT scores could be explained by inter‐group variance in TRP values.As we observed significant differences in both AUT scores and TRP changes at parietal sites between patients with chronic pain and healthy subjects, we tested in a final step whether TRP differences at parietal electrode sites could explain the group difference in AUT scores. As this mean TRP value correlated significantly with AUT scores, t tests with the independent variable Group  and the dependent variable averaged alpha power at the electrode sites P4 and P8, separately for the reference phase and for the creative ideation phase. Patients with chronic pain showed significantly lower alpha power during the reference phase  than healthy controls , t(64) = −2.776, p = 0.007, Cohen's d = −0.683. The same pattern of results was found for the activation phase with patients having lower alpha power  than healthy controls , t(64) = −3.403, p = 0.001, Cohen's d = −0.838.Given that a number of recent findings pointed to enhanced resting‐state alpha activity for broader aspects of chronic pain (Pinheiro et al., 4Attentional deficits are common in patients with chronic pain, and several studies have shown that chronic pain impairs performance on various attentional tasks (Higgins et al., Our findings are consistent with previous studies that demonstrated the detrimental effects of chronic pain on the performance of more complex cognitive abilities. In addition to the previously established adverse impact of chronic pain on abstractive thinking (Gunnarsson & Agerström, Regardless of these possible confounding variables, impaired creative ideation in patients with chronic pain can have severe consequences for their daily lives, as many activities require and benefit from creative thinking Beaty, . As creaOur findings provide further insight into the underlying mechanisms of creative ideation impairments in patients with chronic pain. Benedek, Schickel et al.  have linAccording to the fallacy of reverse inference pointed out by Poldrack , a partiresting state. This might explain why in the present study alpha power was lower and not larger in patients with chronic pain compared to healthy controls. However, whether this conclusion is tenable would need to be investigated in further studies. Nevertheless, the altered alpha power found in patients with chronic pain could be indicative of functional, attention‐related changes in the brain.However, ERS differences explained the group differences in creative ideas only partially. One explanation could be provided by the finding that patients with chronic pain not only differed in TRP values from healthy controls but also showed significantly different alpha power during both the reference and creative ideation phases. Several studies have demonstrated altered EEG activity in patients with chronic pain at a resting state (for a review see Pinheiro et al., Other explanations that the effect of ERS differences only partially explained the group differences might arise from studies that have shown structural changes in the brains of patients with chronic pain (Baliki et al., In sum, the present study provided evidence that attentional deficits in patients with chronic pain translate into a broader spectrum of cognitive impairments. More specifically, chronic pain impairs internal attention and, thereby, impedes creative ideation. The simultaneous use of behavioural and attention‐related psychophysiological measures allowed us to elucidate the functional relationship between attentional disruption by chronic pain and its impact on creative ideation. As attention also plays a crucial role in many other cognitive abilities, it would be compelling for further studies to explore whether similar mechanisms of the disruptive effects of chronic pain on attention can be identified that lead to these deficits. If such further functional relationships were uncovered, targeted attention‐related interventions could be developed to mitigate the adverse impact of chronic pain in everyday activities (Attridge et al., The authors declared that they have no conflict of interest to disclose.


Chronic pain is often difficult to manage in autosomal dominant polycystic kidney disease (ADPKD) patients and sometimes even leads to nephrectomy. We analyzed the long-term efficacy of our innovative multidisciplinary protocol to treat chronic refractory pain that aims to preserve kidney function by applying among other sequential nerve blocks.Patients were eligible if pain was present ≥3 months with a score of ≥50 on a visual analog scale (VAS) of 100, was negatively affecting quality of life and if there had been insufficient response to previous therapies, including opioid treatment. Treatment options were, in order, analgesics, cyst aspiration and fenestration, nerve blocks and nephrectomy.n = 51) needed additional treatment. At the end of follow-up in only 13 patients (12.9%) was surgical intervention necessary: 11 nephrectomies , 1 liver transplantation and 1 partial hepatectomy. After a median follow-up of 4.5 years (interquartile range 2.5–5.3), 69.0% of the patients still had fewer pain complaints.A total of 101 patients were assessed in our clinic . Eight patients were treated with medication, 6 by cyst aspiration or fenestration, 63 by nerve blocks and 6 received surgery as the first treatment option. Overall, 76.9% experienced a positive effect on pain complaints shortly after treatment. The VAS score was reduced from 60/100 to 20/100 (P < 0.001) and patients decreased their number of nonopioid and opioid analgesics significantly . A substantial number of the patients (These data indicate that our multidisciplinary treatment protocol appears effective in reducing pain in the majority of patients with chronic refractory pain, while postponing or even avoiding in most patients surgical interventions such as nephrectomy in most patients.  KEY LEARNING POINTSWhat is already known about this subject?Chronic pain is often difficult to manage in autosomal dominant polycystic kidney disease (ADPKD) patients and even leads to nephrectomy, which is problematic, because ADPKD is a progressive disease that leads to kidney failure in most patients.What this study adds?In our expertise center for polycystic kidney disease, 101 patients with refractory pain complaints were treated, of which the majority (76.9%) experienced a positive effect on pain complaints shortly after treatment and after a median follow-up of 4.5 years; still, 69.0% of the patients had fewer pain complaints.What impact this may have on practice or policy?Our multidisciplinary treatment protocol, by applying among other sequential nerve blocks, appears effective in reducing pain in the majority of patients with chronic refractory pain, while postponing or even avoiding in most patients surgical interventions such as nephrectomy and  hepatectomy.Pain is common in patients with autosomal dominant polycystic kidney disease (ADPKD) . Around Since cysts are formed not only in the kidneys, but also in the liver in the majority of the patients, and pain can originate from diseases other than ADPKD, careful multidisciplinary assessment is needed to identify the cause and mechanism of pain and to offer the best treatment , 10. In This protocol is based on neuro anatomic knowledge that pain stimuli travel by different pathways to the central nervous system. In case of pain caused by pressure of the enlarged cystic organs on adjacent tissues or by distension of the hepatic capsule, pain stimuli are relayed via the celiac plexus and the major splanchnic nerves, whereas pain caused by distension of the renal capsule, the predominant relaying pathway, is via the aorticorenal plexus , 13. By Our initial results with this protocol were promising. In 2017 we reported that after a median follow-up of 12 months, 81.8% of the 44 patients who received nerve blocks experienced a sustained improvement in pain intensity, indicating that our treatment protocol was effective in providing pain relief in ADPKD patients with chronic refractory pain . HoweverFrom August 2013 to August 2020, patients with ADPKD and chronic, severe pain were screened at the pain clinic of our expertise center for PKDs at the University Medical Center Groningen, The Netherlands. Some patients referred themselves, while others were referred by their treating physician from all over The Netherlands. All screened ADPKD patients were included in this analysis. Indications for referral were pain complaints with a pain score on a visual analog scale  ≥50, that were likely to be ADPKD related, lasting ≥3 months, incapacitating  and with insufficient response to previous pain therapies. The institutional review board concluded that this protocol was exempt from approval because it was considered to be a protocolized introduction of novel clinical care (METc 2013.299).After referral, intake took place by a nephrologist or urologist at the pain clinic of our PKD expertise center as well as by a pain specialist. All patients received a questionnaire before intake, including questions considering medication use, VAS score scale 0–100) and two validated quality-of-life questionnaires . The SF-36 can be divided into two domains: the physical component score (PCS) and the mental component score (MCS). These domains were scored from 0 to 100, with a higher score corresponding with a better quality of life. During intake, pain characteristics, nephrourological symptoms, medication use and medical history were discussed. If patients reported pain in one of their loins, lower back or abdomen, the pain was regarded to be of renal origin. If patients reported pain on the right side in the upper abdomen and behind or immediately below the ribcage, it was regarded to be of hepatic origin. Blood pressure was measured in a supine position with an automated oscillometric device . Blood and urine samples were collected. Per the protocol, magnetic resonance imaging (MRI) without contrast was performed and assessed by a radiologist experienced in PKD to exclude other causes of pain and to determine liver and kidney volume. In addition, a radioisotope renography was performed to exclude postrenal obstruction and afunctional kidneys. After this intake, patients were discussed with a multidisciplinary team to determine the most appropriate treatment according to the treatment protocol  laparoscopic fenestration when pain recurred. In case the patient was KRT dependent and fit for surgery, native nephrectomy was the option of first choice. Treatment effect was assessed by the nephrologist or urologist 4 weeks after intervention and a VAS score was documented. If no dominant cysts were observed, the patient was not KRT dependent and treatment with nerve blocks was indicated, a diagnostic, temporary celiac plexus block was performed at the most painful side under local anesthetic. In short, the patient was placed in a prone position. A 20-gauge 15-cm spinal type needle (Cosman) was advanced from posterior to anterior toward the ventral surface of the L1 vertebral body under fluoroscopic guidance. After the needle position was confirmed by injection of contrast medium, 10 mL of bupivacaine (0.5%) was injected.o C are executed. The time needed to perform a diagnostic celiac plexus block or RFA of the major splanchnic nerves 20–30 min. For both procedures patients are observed closely for 2–4 h postprocedure, including vital signs monitoring, until discharge. If pain relief is observed after the splanchnic RFA block but recurred after a significant period of time, a splanchnic block is repeated. If no substantial pain relief is seen after the diagnostic celiac plexus or splanchnic nerve block, patients underwent catheter-based renal denervation  and categorical data as percentages. A baseline characteristics table was created in which patients were grouped based on the type of treatment they received Table . The dift-tests for normally distributed data and Wilcoxon signed rank test for nonnormally distributed data. VAS score, PCS score, MCS score, blood pressure and defined daily dose (DDD) medication were compared.Differences between preintervention and short-term follow-up and preintervention and long-term follow-up were tested with paired n = 14) experienced spontaneous pain recovery or refused treatment. In one patient, pain was not directly related to ADPKD. Of the remaining patients, a total of 64 patients were treated with nerve blocks, 8 patients were treated with medication and physiotherapy, 6 patients received cyst aspiration and/or fenestration  and 6 patients received surgical interventions as the first therapy   could be achieved by the initial treatment option Table . Of the n = 51). In case a diagnostic celiac block led to significant pain reduction but pain recurred (n = 45), patients underwent a long-term splanchnic nerve block with RFA. Of these 45 patients, 25 (55.6%) needed multiple splanchnic nerve block. There were two reasons to perform repeat splanchnic nerve blocks. First was because the initial RFA block did not achieve sufficient pain relief and another RFA block had to be performed (n = 6). In five of these patients the next RFA block was successful. Second, it could be that pain recurred after an initial successful RFA block (n = 19). In this latter group the median number of splanchnic nerve blocks performed per patient was 3 (IQR 2–4), with 1 patient receiving seven splanchnic nerve blocks, which all had a good effect, but temporary. If pain recurred after an initial successful RFA block, the median time between the intervention and recurrence of pain complaints was 6 months (IQR 3–12). In such cases, pain was initially mild but steadily increased, leading to a repeat block 9 months (IQR 6–13) after the previous block.A substantial part of the overall group of 101 patients needed additional treatment after the initial intervention .n = 14 (13.8%)] nerve blocks did not achieve sufficient pain relief and there was a need for scaling up . Overall, VAS scores were still significantly decreased compared with the VAS scores preintervention (P < 0.001). However, patients reported a lower VAS score shortly after intervention compared with long-term follow-up (P = 0.003)  versus 6 (IQR 3–11), P = 0.001]. In addition, an increase in mental health status was observed  and no differences were noticed in physical health . When analyzing the treatment subgroups separately, similar results were observed. However, in the nerve block subgroup, PCS at long-term follow-up was significantly better compared with preintervention .n = 4) experienced orthostatic hypotension or diarrhea after the first diagnostic celiac plexus block, but these adverse events were all self-limiting. In case blood was aspirated during the nerve block, the procedure was interrupted and repeated after 4 weeks . A number of patients (n = 11) experienced the procedure, which was performed under local anesthesia, itself as painful. However, these procedures could all be finished successfully and procedure-related pain was only short-lasting and needed no intervention. In one of the five renal denervation procedures, the procedure was stopped because of a spasm of the renal artery. This intervention was repeated successfully 3 months later. No late complications occurred after the renal denervation procedures. Renal denervation resulted in a decrease in systolic blood pressure , but not in diastolic blood pressure . No complications were noted in patients who received cyst aspiration, cyst fenestration or nephrectomy.Some adverse events were observed after the diagnostic celiac blocks and splanchnic RFA blocks. A small number of patients  that in most cases was successful (n = 16). Third, analgesic use was lower during long-term follow-up compared with short-term follow-up. Dealing with pain complaints is a delicate balance. It may be that the side effects of the analgesics outweighed the advantages of pain relief [To address these limitations, we evaluated in the present study long-term follow-up of all patients with chronic refractory pain who were treated in our PKD expertise center. After a median follow-up time of 4.5 years, significant pain relief was observed, assessed as a decrease in VAS score as well as a decrease in the use of opioids and nonopioids. It should be noted that patients experienced a slightly higher VAS score at the long-term follow-up compared with shortly after the intervention. This minor increase in VAS score, however, had no negative effect on quality of life, and patients experienced even fewer depressive symptoms and better mental health status at the end of follow-up when compared with preintervention. This higher VAS score may have several reasons. First, chronic pain may have recurred after a new acute pain event, such as a cyst bleeding, infection or kidney stone. It is assumed that acute pain events can contribute to chronic pain due to central sensitization . Also inful n = 1. Third, n relief , 19. Copn relief , 20. Toln relief .Some minor adverse events were reported after the various treatment procedures. However, no procedure-related severe adverse events were observed. As mentioned before, pain sensation can be impaired after treatment with nerve blocks and patients may therefore present with different symptomatology when suffering from abdominal diseases, which may delay making a correct diagnosis , 16, 22.We observed that a substantial part of our study population is KFRT dependent 23.5%). It is sometimes assumed that chronic refractory pain in ADPKD is less common in KFRT-dependent patients, since kidney volume decreases after kidney transplantation or starting dialysis .5%. It i. The higRemarkably, in 14 patients the diagnostic celiac block resulted in substantial and sustained pain relief, in some patients even up to 7 years. This was unexpected, because lidocaine, the local anesthetic that is used for this procedure, is only able to block the sensory pathway temporarily. A possible explanation for this finding may be an effect on central sensitization caused by a short period of extreme nociceptive stimulation in the past, e.g. from a cyst infection or cyst bleeding. We assume that by applying local anesthetics, the continuous excitation of visceral nociceptive neurons is temporarily interrupted, allowing the neurons to return to their normal resting potential .The aim of our protocol was to avoid or postpone nephrectomy in a disease that leads to kidney failure in most affected subjects . A nephrWhat may be the consequences of our findings? In our multidisciplinary protocol we performed individualized patient care. All patients were discussed by the multidisciplinary team and, based on the assessment by representatives of the various disciplines, the most kidney function-sparing treatment option was chosen with the a priori best chance of success. Our evaluation showed that this strategy is effective in reducing pain in the majority of patients with chronic refractory pain. Given the favorable efficacy:safety ratio, we propose that this protocol should be incorporated in clinical care. Because expertise and experience are needed by the various disciplines involved, and because the incidence of chronic, refractory pain is limited, we propose that implementation should be limited to PKD expertise centers. Furthermore, given the favorable efficacy:safety ratio, offering nerve blocks to ADPKD patients with less severe kidney-related pain should be considered, as well as to non-ADPKD patients. Other patients with chronic, refractory kidney pain related to a nonmalignant and noninfectious cause, such as loin pain hematuria syndrome or symptomatic parapelvic cysts, may also benefit , 25.Of note, renal denervation was not available as a treatment option for patients from 2016 to 2021 because ablation catheters were no longer available due to the disappointing results of the Simplicity trials . RecentlThis study has limitations, of which the most important is that it is a nonrandomized single-center experience. Short-term benefit akin to a placebo effect can therefore not be excluded. We chose to perform our protocol in such a setting because we considered it unethical to perform sham procedures in patients with chronic refractory pain, in line with the literature on placebo anesthetic blocks . Second,In conclusion, our multidisciplinary stepwise treatment protocol is effective in reducing pain in the majority of patients with chronic refractory pain and contributes to quality of life, while avoiding in nearly all patients surgical interventions such as nephrectomy of a functioning kidney and  hepatectomy. We propose that our protocol should be implemented in the clinical care of PKD expertise centers and, given the satisfactory efficacy:safety ratio, also ADPKD patients with less severe pain may be eligible, and even non-ADPKD patients with similar complaints.gfac158_Supplemental_FilesClick here for additional data file.