The Chronic Pain Coping Inventory-42(CPCI-42) is mainly used for chronic pain management project, its original version is written in English and has been widely used in western countries. Therefore, the purpose of our study is to apply the CPCI-42 to Chinese patients and evaluate its responsiveness, reliability, and validity for Chinese patients with lumbar disc herniation (LDH).Translation and adaptation were carried out in accordance with the guidelines of the American Academy of Orthopedic Surgeons Outcome Committee. A total of 133 patients who were diagnosed with LDH were included in this study. Psychometric evaluations were then performed and included score distribution, internal consistency, test–retest reliability, construct validity, and responsiveness.CPCI-42 is well adapted to the assessment of the cognitive and behavioral strategies of patients with LDH, and the scores of score distribution, internal consistency, test–retest reliability, construct validity, and responsiveness are excellent. Forward and reverse translation of the CPCI-42 to English from Chinese worked smoothly.It is applicable to the assessment of quality of life of the cognitive and behavioral strategies of patients with LDH, and the scores of all indicators are excellent. Lumbar disc herniation (LDH) is the most common cause of low back pain. The main signs and symptoms include low back pain, numbness and pain of one or both lower limbs. Focal paralysis, limitation of trunk flexion, and increased leg pain when sitting or coughing and sneezing forcefully may also indicate LDH . The oveThe Chronic Pain Coping Inventory-42(CPCI-42) is mainly used for chronic pain management project, which is often used to evaluate the eight types of coping strategies that patients may use to cope with chronic pain, and has been widely used in western countries  and PoliThe English version of CPCI-42 was translated into simplified Chinese in accordance with the principles of the guidelines previously issued . The whoWe recruited 163 patients with chronic low back pain caused by LDH from outpatients and inpatients of our Hospital. Inclusion criteria are as follows: (1) age > 18, with independent signature right; (2) patients with LDH diagnosed by MRI and the severity is Grade I and Grade II; (3) chronic pain for more than 3 months and/or recurrent back pain with/without radiation pain. The exclusion criteria are as follows: (1) patients with other diseases that cause chronic pain, (2) patients who are receiving conservative treatment or have undergone surgical treatment. All participants read and signed the informed consent form approved by the Ethics Committee. On the first day of admission, patients were asked to provide demographic information and independently completed two scales  in a quiet conference room. One week after the completion of the first set of scales, they completed SC-CPCI-42 for the second time before starting conservative treatment to evaluate the scale of test–retest reliability. If the patient received relevant treatment in the previous week, they will be excluded. Finally, patients receiving 12 weeks of conservative treatment in our hospital completed SC-CPCI-42 for the third time to assess responsiveness. Finally, 133 patients participated in the whole experiment and were included in our analysis.CPCI-42 is a 42 item abbreviated version of CPCI, which evaluates cognitive and behavioral strategies for coping with chronic pain . The 42 The Wong Baker FACES Pain Rating Scale (WBS) uses all five emoticons to assess the range of pain intensity , WBS is α value of the scale. When α > 0.7, 0.8, and 0.9, the scale has acceptable, good, and excellent internal consistency, respectively [Reliability is the degree to which the measurement is free from error. The reliability test of SC-CPCI-42 mainly includes internal consistency, and test–retest reliability . The degectively .r > 0.8), ‘very good’ (r = 0.61–0.80), ‘moderate’ (r = 0.41–0.60), ‘fair’ (r = 0.21–0.40), and ‘poor’ (r < 0.20 or P > 0.05).The validity of SC-CPCI-42 can be evaluated by its content validity and construct validity. The comprehensiveness and evaluation of the relevance of the items are evaluated by content validity. The comprehensive evaluation indexes of the three items are patients’ feedback, the response rate, and ceiling/floor effects. Assuming that the ceiling/floor effect is less than 15%, the patient's feedback is greater than 95%, and the patient reports no difficulty in filling out the scale, the judgment scale is considered to have great comprehensiveness . The PeaResponsiveness is a scale used to detect the ability of structures to be measured over a period of time . The resThe analyses were performed in SPSS version 25.0 for Windows . The data are expressed as the mean and standard deviation (SD). The 95% confidence intervals (CIs) report the ICC value. A P value less than or equal to 0.05 is considered statistically significant.All procedures performed in this study involving human participants were carried out in accordance with the 1964 Helsinki Declaration and its later amendments or comparable ethical standards. All participants read and signed informed consent, and this clinical study obtained the approval of the ethics committee of our hospital.A total of 163 patients with chronic low back pain caused by LDH met the screening criteria. In the end, 133 patients participated in the whole study. Therefore, 133 samples were selected to evaluate the validity, test–retest reliability, responsiveness, test–retest reliability and internal consistency of SC-CPCI-42. Table This section may be divided by subheadings. It should provide a concise and precise description of the experimental results, their interpretation, as well as the experimental conclusions that can be drawn.Forward and reverse translation of SC-CPCI-42 worked very smoothly. Since the items of the SC-CPCI-42 are easy to understand, we did not improve them. None of the patients indicated that the project was difficult to understand. There was no lack of standardization.In this study, there was no error in SC-CPCI-42. The score distribution shows that there is no floor effect or ceiling effect in SC-CPCI-42. According to the correlation strength among 42 items, the internal consistency of SC-CPCI-42 is good, and each item is correlated with its subscale table Table .Table 2DThere were no errors in the SC-CPCI-42 questionnaire in this study. The score distribution shows that there is no ceiling and floor effect in SC-CPCI-42 score (Table The questionnaire was completed before and after conservative treatment to evaluate the responsiveness of SC-CPCI-42. The relevant data are shown in Table Through this study, it is found that SC-CPCI-42 shows good score distribution, high internal consistency, excellent test–retest reliability, and significant structural and discriminant validity. As far as we know, this is the first time to apply CPCI-42 translation, cross-cultural adaptation and research to people in Chinese Mainland. It complements the previous research to a certain extent , and appα are high in the eight projects of SC-CPCI-42, which shows that they have a strong correlation with each other. In the Korean version of the scale, Cronbach α of asking for assistance is relatively low, which may be due to cultural differences among Koreans [α of the Chinese version of asking for assistance in SC-CIPI-42 is relatively high. Good test–retest reliability is reflected in SC-CIPI-42, which is consistent with the results of similar studies. There is no floor effect or ceiling effect in SC-CIPI-42. The evaluation of the three experts also confirmed that the SC-CIPI-42 project is closely related to the prognosis of chronic pain in patients with LDH. In addition, because SC-CIPI-42 is easy to understand, there is no missing reply in any returned questionnaire.The study have shown that Cronbach  Koreans . Many KoThe test–retest reliability evaluation of SC-CIPI-42 was conducted at the interval of one week. The patient is unlikely to remember the specific answers in the previous questionnaire completely, and the functional status and daily life of the patient will not change significantly within one week.In terms of the correlation between the SC-CIPI-42 of WBS, each subfield of SC-CIPI-42 is very good or excellent. WBS expresses pain in an intuitive way, and uses the number range to convey the patient's pain experience in the context of facial expressions. CIPI-42An important factor in determining whether the scale can be used in prospective clinical research is the quality of scale responsiveness . In thisAccording to our results and the data of other language versions, CIPI-42 is well adapted to the assessment of cognitive and behavioral strategies for coping with chronic pain, and the scores of various indicators are excellent. Although there are still some deficiencies in our research, the subjects of our study are all patients with lumbar disc herniation of grade I and II severity, who receive conservative treatment. It needs further study on the evaluation results of the pain of LDH with grade III severity and requiring surgical treatment.In short, CIPI-42 was successfully translated into Chinese. After verification, the version was easy to use and shown to have good responsiveness, reliability, and effectiveness. SC-CIPI-42 is well adapted to assess the cognitive and behavioral strategies of patients with LDH for chronic pain.


Although neuropathic pain is a significant problem in polyneuropathy, the underlying molecular mechanisms are poorly understood. The endogenous bioactive lipids 2-arachidonoyl-glycerol (2-AG), oleoylethanolamide (OEA), palmitoylethanolamide (PEA), and stearoylethanolamide (SEA) are known to influence pain and inflammation in the peripheral nervous system. The aim of this study was to explore the plasma levels of endocannabinoids and related lipids and health-related quality of life in patients with polyneuropathy with and without pain.n = 48) with Chronic Idiopathic Axonal Neuropathy were included. Clinical data were retrieved from medical files. All patients filled out the SF-36 and EQ-5D questionnaires. In addition, blood samples were analyzed for 2-AG, OEA, PEA, and SEA.Patients (P = 0.03), but there were no significant differences in OEA (P = 0.61), PEA (P = 0.95), or SEA (P = 0.97) levels. The patients reporting pain in the hands had significantly lower SEA levels, 10.0 versus 15.0 (P = 0.03). The levels of 2-AG were significantly higher among patients reporting paresthesia in their feet . Levels of PEA, SEA, and 2-AG were decreased in patients with loss of vibration. PEA and SEA were decreased in patients with loss of pain and temperature, and SEA decreased in patients with loss of sense of touch. However, the differences in the levels of bioactive endogenous lipids were not statistically significant when corrected for multiple comparisons.Neuropathic pain was reported in 21 of the patients. There were significantly lower levels of 2-AG in patients with neuropathic pain (Alterations of 2-AG levels between polyneuropathy patients with and without neurogenic pain indicate that it could play an essential role. Further studies are warranted. Neuropathies are common peripheral nervous system disorders affecting at least 4% of the general middle-aged and elderly population . The cliNeuropathic pain is defined by the International Association for the Study of Pain (IASP) as ‘pain caused by a lesion or disease of the somatosensory nervous system’ . Since tThe molecular mechanisms behind the pain mechanisms in polyneuropathy are poorly understood. The ‘gate control theory’ of pain has, since its formulation in 1965, postulated that neuronal circuits in the central nervous system (CNS) regulate nociceptive signals arising in the periphery of the body . The desEndogenous bioactive lipid mediators modulate the immune system  and inflNaturally occurring N-acyl ethanolamines have been widely studied in the context of neuroinflammation and neuropathic pain in recent years . NeuronsChronic widespread pain (CWP) is often associated with fibromyalgia syndrome. Central alterations in CWP may be driven by peripheral alterations in muscles , 24 and/There is a lack of knowledge about bioactive endogenous lipids in CIAP, and we hypothesize that they play an essential role in the regulation of pain. Hence, the aim of this study was to investigate the plasma levels of ECs and related lipids  and health-related quality of life in patients with polyneuropathy with and without neuropathic pain.n = 255) were screened at the neurology departments at Linköping University Hospital and Ryhov Hospital in Jönköping, Sweden. Inclusion criteria were aged 40–79 years at diagnosis of CIAP. The patients were interviewed and examined at diagnosis according to clinical routine. We defined polyneuropathy as at least one typical polyneuropathy symptom and at least one of the clinical findings . The following laboratory investigations had to be normal to consider it as CIAP: hemoglobin, serum glucose, cobalamin, folate, and thyroid function.This study’s subjects have previously been included in studies of clinical data and exposures in polyneuropathy , 29–32. Nerve conduction studies were not required, but they had to show axonal or combined axonal and demyelinating findings if performed. Patients with dominantly demyelinating neurophysiological findings alone or conduction block were excluded. Patients under the age of 40 were not included to avoid genetic or toxic polyneuropathies not yet diagnosed. Forty-eight patients fulfilled the criteria and gave consent to participate in this study. Blood samples and questionnaires were obtained after the written informed consent. Neuropathic pain was defined according to IASP . The paiThe regional ethical committee in Linköping approved the study (Dnr 99353 and Dnr 01-443), and the patients included gave their written informed consent.The following data were retrieved from medical files: age, sex, year of first symptom and year of diagnosis, reported symptoms, clinical findings at the first visit, and neurophysiological findings. The severity of polyneuropathy was based on Perinea’s classification : ‘1 = miOf the 48 patients, 38 underwent neurophysiological testing to establish a diagnosis of axonal polyneuropathy and to exclude demyelinating polyneuropathy  .N-Acylethanolamines and 2-AG were analyzed in plasma samples using liquid chromatography tandem mass spectrometry (LC-MS/MS), based on a previously published method (2O containing 0.133% trifluoroacetic acid (TFA). C8 Octyl solid-phase extraction columns   were used for further extraction. Before adding the sample to the column, they were activated with methanol (1 mL) and washed with millQ-H2O (1 mL), following a wash with 1.5 mL ACN (20% with 0.1% TFA). Elution was performed with 1.5 mL ACN (80% with 0.1% TFA). SpeedVacc then dried the eluate. The samples were reconstituted in 30 μL of LC mobile phase on analysis day, and 10 μL was the volume injected into the LC-MS/MS system.d method . Lipid ed method . SamplesR2 ≥ 0.9 was the linearity for all analytes. All standards were purchased from Cayman Chemicals. The analytes were quantified using isotopic dilution according to the area ratio of their corresponding deuterated internal standard signal area. AEA-d4 corresponded for OEA, PEA, SEA, and 2-AG-d5 for 2-AG. Equal weighting and linear regression were applied. Peak integration and quantification were performed using the Xcalibur®  software.An LC-MS/MS system containing a Thermo Scientific Accela AS autosampler and Accela 1250 pump coupled with a Thermo Scientific TSQ Quantum Access max triple quadrupole mass spectrometer with a HESI II probe as an ionization source was used. LC and MS/MS parameters were as in Ref. . The selAll patients filled out the SF-36 and EQ-5D questionnaires. Complete information about the methodology is described in earlier publications . Eight st-test was performed. Because the SF-36 and the EQ-barometer scales are categorical and not normally distributed, the Kruskal–Wallis test was used, followed by Mann–Whitney U test. For EQ-5D, the Chi-2 test was used. The analysis was completed with Fischer’s exact test for groups with fewer than five respondents. Correlations were tested using Spearman’s rank correlation. Differences were considered significant if P-values were <0.05. For multiple comparisons, correction according to Bonferroni was performed.Statistical analysis was performed using Statistica . Data in text and figures are expressed as mean (standard deviation [SD]). For pairwise analysis of interval, a data Of the 48 patients included, 21 had symptoms and clinical findings of neuropathic pain. Patient characteristics are described in P = 0.028), but there were no significant differences in OEA, PEA, or SEA levels (P < 0.001), as well as OEA and SEA , PEA and SEA , and SEA and AG . There was no correlation between 2-AG levels and levels of OEA and PEA. Age was affecting levels of OEA , but not PEA, SEA, or 2-AG.There were significantly lower levels of 2-AG in patients with neuropathic pain (A levels . The difP = 0.03). The levels of 2-AG were significantly higher among patients reporting paresthesia in their feet . There were no other significant differences in levels of OEA, PEA, SEA, or 2-AG for any other symptoms from hands or feet.The 16 patients reporting pain in the hands had significantly lower SEA levels, 10.0 (3.5) versus 15.0 (8.6) , and other SF-36 variables OEA, PEA, and 2-AG were not correlated with clinical severity. Neither EQ-5D index nor EQ-VAS was correlated with OEA, PEA, SEA, or 2-AG levels. Neurophysiological severity was not correlated to any SF-36 or EQ-5D variables.There were no significant correlations between SF-36 variables and levels of OEA, PEA, SEA, or 2-AG. PF, role physical, and PCS decreased with increasing clinical severity physiological functions, such as emotion, cognition, energy balance, pain sensation, and neuroinflammation . 2-AG isTonic release of endogenous PPAR-α agonists in healthy tissues, such as PEA and OEA, may help to set the threshold for nociception by regulating the baseline transcriptional activity of the NFκB complex and the opening of membrane ion channels in primary sensory afferents and nearby host-defense cells . A tempoConcentrating on endogenous regulators of neuroinflammation may be a feasible therapeutic approach for nervous system disorders by targeting non-neuronal cells. There are substantial CB1 levels in nociceptive and non-nociceptive sensory neurons of the dorsal root ganglions . MoreoveIt has been suggested that OEA and PEA exert a tonic inhibitory control over the inflammatory and nociceptive responses . Our datThere has been great hope for cannabinoids as a treatment for neuropathic pain. However, data are still limited . In animThis is the first exploratory study of bioactive endogenous lipids in CIAP with clinical data and the patients’ perceived health-related quality of life. The differentiation between neuropathic and non-neuropathic pain was done from medical records. A prospective study using stringent criteria for neuropathic pain should be performed in the future. Our results are limited due to the low sample size and the lack of a healthy control group. The decreased levels of bioactive endogenous lipids in some symptoms and clinical findings should be interpreted with great caution as they were not statistically significant when corrected to multiple comparisons. However, our data mandate further studies.Neuropathic pain presents a significant burden to individuals and society. There is a need for a better understanding of underlying mechanisms. Earlier reports on neuropathies and ECs have mainly been based on animal models. Alteration of 2-AG levels between polyneuropathy patients with and without neurogenic pain indicates that 2-AG could play an essential role in neurogenic pain in patients with polyneuropathy.The authors report no conflicts of interest in this work.This study was supported by grants from the Swedish Research Council (2018-02470), County Council of Östergötland , and Futurum, Region Jönköping County. The sponsors had no role in study design, data collection, data analysis, data interpretation, writing of the report, or the decision to submit for publication. The authors had full access to all the data in the study and had final responsibility for the decision to submit it for publication.The datasets generated and/or analyzed in this study are not publicly available as the Ethical Review Board has not approved these data’s public availability.All authors made substantial contributions to conception and design, acquisition of data, or analysis and interpretation of data; took part in drafting the article or revising it critically for important intellectual content; agreed to submit to the current journal; gave final approval of the version to be published; and agree to be accountable for all aspects of the work.Jonas Lind, M.D., Ph.D. is a Consultant Neurologist at the Department of Neurology, Internal Medicine, County Hospital Ryhov, Jönköping and an Adjunct Senior Lecturer at the Division of Neurobiology, Department of Biomedical and Clinical Sciences, Linköping University, Linköping, Sweden.Niclas Stensson, M.Sc., Ph.D is affiliated with the Pain and Rehabilitation Centre, and Department of Health, Medicine and Caring Sciences, Linköping University, Linköping, Sweden.Björn Gerdle, M.D., Ph.D. is a Professor emeritus and a Consultant at Pain and Rehabilitation Centre, and Department of Health, Medicine and Caring Sciences, Linköping University, Linköping, Sweden.Nazdar Ghafouri, M.D., Ph.D., is a Consultant Physician at Pain and Rehabilitation Centre, and Department of Health, Medicine and Caring Sciences, Linköping University, Linköping, Sweden.https://orcid.org/0000-0001-5357-3767Jonas Lind https://orcid.org/0000-0001-6081-9673Niclas Stensson https://orcid.org/0000-0002-4316-1264Björn Gerdle https://orcid.org/0000-0001-8789-0656Nazdar Ghafouri


Long-term follow-up after bariatric surgery (BS) reveals high numbers of patients with abdominal pain that often remains unexplained. The aim of this prospective study was to give an overview of diagnoses for abdominal pain, percentage of unexplained complaints, number and yield of follow-up visits, and time to establish a diagnosis.Patients who visited the Spaarne Gasthuis Hospital, The Netherlands, between December 2020 and December 2021 for abdominal pain after BS, were eligible and followed throughout the entire episode of abdominal pain. Distinction was made between presumed and definitive diagnoses.p < 0.001). Patients with IBS more often had unexplained complaints . At the end, 71 patients (16.1%) still experienced abdominal pain.The study comprised 441 patients with abdominal pain; 401 (90.9%) females, 380 (87.7%) had Roux-en-Y gastric bypass, mean (SD) % total weight loss was 31.4 (10.5), and median (IQR) time after BS was 37.0 (11.0–66.0) months. Most patients had 1–5 follow-up visits. Readmissions and reoperations were present in 212 (48.1%) and 164 (37.2%) patients. At the end of the episode, 88 (20.0%) patients had a presumed diagnosis, 183 (41.5%) a definitive diagnosis, and 170 (38.5%) unexplained complaints. Most common definitive diagnoses were cholelithiasis, ulcers, internal herniations, and presumed diagnoses irritable bowel syndrome (IBS), anterior cutaneous nerve entrapment syndrome, and constipation. Median (IQR) time to presumed diagnoses, definitive diagnoses, or unexplained complaints was 16.0 (3.8–44.5), 2.0 (0.0–31.5), and 13.5 (1.0–53.8) days (Over a third of abdominal complaints after BS remains unexplained. Most common diagnoses were cholelithiasis, ulcers, and internal herniations.The online version contains supplementary material available at 10.1007/s11695-023-06756-3. The global prevalence of obesity is increasing, which impacts the number of bariatric surgeries performed –3. BariaThe self-reported prevalence of abdominal pain after BS varies between 33.8 and 54.4% –9. AbdomLiterature on the diagnoses of abdominal pain during outpatient clinic and emergency department visits among patients after BS is limited. Crucially, follow-up of the abdominal pain after first visits is lacking, as is insight into the magnitude of the group with unexplained complaints at the end of the follow-up. The aim of this study is to provide the first overview of the diagnoses of abdominal pain in patients after BS and the percentage of unexplained complaints at initial presentation and after follow-up. In addition, number and yield of follow-up visits and the time between first visit and the diagnosis are examined. Finally, it is examined whether the complaints were resolved or persisted at the end of follow-up.The OPERATE  study is a prospective cohort study to evaluate multiple aspects of abdominal pain in patients after BS, at the Spaarne Gasthuis Hospital Hoofddorp, a dutch bariatric center. At our hospital, we have our own multidisciplinary team and 24/7 on call bariatric service. We perform 800 surgeries annually, with four bariatric surgeons, each with over 12 years of experience. Inclusion started in December 2020 and is ongoing. The entire episodes of all patients with abdominal pain after BS visiting the outpatient clinic or emergency department of the Spaarne Gasthuis are included. Figure The current substudy included patients who visited the hospital for abdominal pain between December 2020 and December 2021. Only the first episode of each patient with abdominal pain within this study period was included. In conclusion, in this study, each patient represents one episode. Ongoing episodes after November 1st, 2022, were excluded.At the end of each visit and/or episode, it was assessed whether a patient met the criteria for one or more diagnoses. A distinction was made between presumed diagnoses and definitive diagnoses Table . Two barPrimary outcome measures are the number of presumed diagnoses, definitive diagnoses, and unexplained complaints for abdominal pain in patients after BS during the first visit and at the end of an episode. Secondary outcomes are (1) the number of follow-up visits and their yield in the diagnostic process, (2) the number and duration of readmissions and number of reoperations, (3) the time it takes to establish a presumed diagnosis or definitive diagnosis, (4) the timeline between BS and the various diagnoses of abdominal pain, and finally, (5) whether complaints have resolved at the end of an episode.Baseline characteristics were collected from electronic patient records. Emergency department visits, readmission, and reoperations for abdominal pain after BS, before the start of the study period, were recorded. Before the start of the study, standardized reporting by the radiologist or gastroenterologist was implemented for abdominal CT-scans, ultrasounds, gastroscopies, barium swallow X-rays, and abdominal X-rays. Bariatric surgeons also completed a standardized surgery report in case of a reoperation. All data was stored in an electronic case record form in a web-based data capture-system (Castor EDC). The database was anonymized by a study number. Three researchers  having exclusive access to the database gathered the data and are able to re-identify patients based on their study number.t-test, the non-parametric Mann-Whitney U test, or Kruskal Wallis test, depending on their distribution. The chi-square test was used for categorical variables. Logistic regression analysis was used to evaluate associations between patient characteristics and diagnoses. Variables with a p value of 0.10 or less in the univariable analysis were selected for the multivariable model. Stepwise backward elimination was used to derive a final model: in each subsequent step, the least significant variable in the model was removed until all remaining variables had individual p values smaller than 0.10. All p values are two-sided, and p values below 0.05 were considered statistically significant. Data were analyzed using Statistical Package for Social Sciences (SPSS) version 24 for windows . Tables and figures were made using Microsoft and SPSS.Data were reported as mean and standard deviation (SD) for normally distributed variables and as median and interquartile range (IQR) for variables with a skewed distribution. Continuous variables between groups were compared using the independent sample p < 0.001).From December 2020 until December 2021, 448 patients after BS visited the hospital for abdominal pain. Seven patients were excluded: three patients with incomplete episodes, two patients who were simultaneously treated in another hospital, and two patients with unclear anatomy of the gastric bypass. Baseline characteristics of the remaining 441 patients are presented in Table At the end of the episode, 88 (20.0%) patients had a presumed diagnosis, 183 (41.5%) patients a definitive diagnosis, and 170 (38.5%) patients had unexplained complaints. Twenty-six patients had more than one diagnosis at the end of the episode. In 12 patients, the second or third diagnosis was a complication of the first diagnosis, for instance, bile leakage after cholecystectomy. The remaining patients had two or three unrelated diagnoses during their episode.Internal herniation and cholecystolithiasis were the most common presumed diagnoses during first visit Fig. . The mosA total of 136 patients (30.8%) had only one follow-up visit, whereas the majority had two to five follow-up visits in descending order . Internal herniation, cholecystolithiasis, and appendicitis were usually diagnosed during the first visit or first follow-up visit. Anterior cutaneous nerve entrapment syndrome (ACNES), abdominal wall herniation, IBS, and constipation were usually diagnosed later on in the episode .Median (IQR) time to a presumed diagnosis, definitive diagnosis, or unexplained complaints from the start of the episode was 16.0 3.8–44.5), 2.0 (0.0–31.5), and 13.5 (1.0–53.8) days, respectively , p = 0.062). Patients with IBS had a significant higher probability of unexplained complaints when compared to patients with a definitive diagnosis . A lower BMI at first presentation, IBS, and previous abdominal surgery were associated with a presumed diagnosis if compared to patients with a definitive diagnosis .The multivariable model on the association between patient characteristics and diagnosis (presumed diagnoses/definitive diagnoses or unexplained complaints) revealed that patients with IBS more often had unexplained complaints at the end of the episode compared to patients without IBS  still experienced abdominal pain of which 29 (40.1%) had unexplained complaints. In 96 (21.7%) patients, it was not clear whether complaints had been resolved due to lack of follow-up or wait-and-see policy. Patients with IBS were most likely to have persistent complaints and in 5 (8.3%) patients treated for cholecystolithiasis complaints persisted without an alternative diagnosis. Data is shown in Supplemental Tables This is the first prospective study on the diagnoses of abdominal pain after BS which included the entire follow-up. In this study, a diagnosis for abdominal pain was found in 61.5% of patients, whereas 38.5% had unexplained complaints at the end of the episode. Most common diagnoses were cholecystolithiasis, ulcer, internal herniation, IBS, ACNES, and constipation. Majority of patients had one to five follow-up visits, but the diagnosis was usually established during the first four visits. Definitive diagnoses were set significantly earlier than presumed diagnoses and unexplained complaints. We did not observe an association between specific diagnoses and time after initial BS. Patients with unexplained complaints more often had a history of IBS. At the end of the episode, abdominal pain persisted in over 15% of patients and resolved in 62.2%.In a systematic review on emergency department visits and readmissions after BS, only one study reported emergency department visits beyond 90 days after surgery, with 31.1% emergency department visits 3 years after RYGB , 21. TheInternal herniation, cholecystolithiasis, and ulcers were the top differential diagnoses during the first visit and turned out to be the most common diagnoses at the end of the episode. These three diagnoses were established early in the diagnostic process. In contrast, IBS, ACNES, and constipation were often diagnosed later in the episode. This may be explained by unspecific symptoms and the need for physicians to rule out potentially life-threatening causes for abdominal pain first. A retrospective cohort study compared symptoms in patients with unexplained complaints to patients with a specific diagnosis. The kind of pain  and stool pattern were the only significantly differences between groups . This suIn patients after BS, many diagnostic tests are performed in the diagnostic process of abdominal pain , 26. FurThe current literature shows (chronic) abdominal complaints in 33.8–54.4% after BS of which 4.5–53% sought medical help for these complaints , 9, 28. In the analyses of this study, we did not take into account whether patients had abdominal pain before BS. According to a study by Hogestol et al., 18.5% of patients with chronic abdominal pain also had complaints prior to surgery . In anotOut of the scope of this article, but remarkable, is the fact that many patients experience all kinds of other gastrointestinal symptoms in addition to abdominal pain , 29, 30.All previous visits, readmissions, reoperations, and diagnoses for abdominal pain before the start of the study are not included in the analyses. This makes the study less comparable to current retrospective cohort studies. On the other hand, this design results in a larger group of patients, and it better reflects daily practice in the outpatient clinic and emergency department. In patients with previous unexplained complaints, more acute causes were possible already ruled out during earlier episodes. Therefore, the diagnostic process could have focused more on another set of diagnoses than in patients with a first presentation for abdominal pain. Future research on sequential episodes in the OPERATE study will provide more information on the impact of these patients. This study was started in the COVID pandemic. This could have impacted the number of visits and the duration of the episodes. The numbers of several diagnoses were too small to evaluate in what time after surgery they occurred. Furthermore, although no associations were observed between type of operation and outcomes, Roux-en-Y gastric bypass is still the number one of BS performed in the Netherlands, and there are too little sleeve gastrectomies and one-anastomosis gastric bypass surgeries to compare with. This is important because current literature shows that the numbers of emergency department visits and readmissions for abdominal pain after sleeve gastrectomy are quite similar to those of the Roux-en-Y gastric bypass . Lastly,Most common diagnoses for abdominal pain after BS were cholelithiasis, ulcers, internal herniations, IBS, ACNES, and constipation. However, over a third of abdominal pain remains unexplained, and at the end of the episode, over 15% of patients continues to have complaints. In the future, people with an acute cause for abdominal pain, such as an internal herniation, should be better distinguished from patients with transient or chronic complaints to prevent unnecessary visits, diagnostic tests, and reoperations. Therefore, there is a need for an algorithm to better distinguish, diagnose, and ultimately treat patient, one of the main goals of the OPERATE study.Supplementary file1 (DOCX 21 KB)Supplementary file2 (DOCX 22 KB)Supplementary file3 (DOCX 24 KB)Below is the link to the electronic supplementary material.


Assess whether the spine surgical approach for degenerative diseases can influence the physical capacity of patients and its correlation with cardiorespiratory function.A prospective study was conducted on 9 patients of both genders, aged between eighteen and sixty, scheduled for spinal surgery for degenerative disease in the lumbar segment. Patients underwent treadmill stress test two times, fifteen days before and sixty days after the surgery. A cardiologist performed the test according to the Bruce protocol with a progressive increase in incline and speed.There were no statistically significant differences between pre- and postoperative assessments for the parameters evaluated in the treadmill stress test. Forty-four percent of patients needed to interrupt the test postoperatively due to dyspnea (p=0.023).Level of Evidence II; Lesser quality RCT .The improvement obtained with spinal surgery does not have statistically significant relevance in tiredness, pain, and fatigue in the lower limbs and low back pain. Some patients could not complete the examination after surgery due to poor physical conditioning, and it was necessary to interrupt the examination due to dyspnea.  Low back pain is considered chronic if lasts longer than six months. It is estimated that 70 to 85% of the world's population will experience back pain at some point in their lives. In Brazil about ten million of Brazilians suffer with disabilities caused by low back pain, which is considered a public health problem. LBP can be caused by several factors, such as inflammation, muscle weakness and degenerative diseases. Disc degeneration is related to environmental effects, injuries caused by trauma, smoking, atherosclerosis and the natural aging. The lumbar spine is divided according to its functional capacity; in anterior, middle, and posterior. The anterior portion of spine is made up of the intervertebral discs and vertebral bodies. The middle portion consists of the spinal canal and pedicles. The posterior portion is responsible for directing the functional units in the movements of anterior/lateral flexion, extension and rotation. The intervertebral disc works as a hydraulic system, absorbing shock and distributing the load evenly. Thus, the amount of water in its composition it is proportional to its absorption capacity. Interverterbal disc collagen production occurs in three phases: the initial one, where there is abundant collagen production; the maturation phase, which maintains collagen renewal; and, finally, the degenerative phase, where there is a decrease in renewal. As it is an avascular structure, the nutrition of the disc occurs by diffusion. Anatomically described, the soluble regulators of cell function indicate the aging and senescence of the disc - which consists of a nucleus pulposus surrounded by an annulus fibrosus. The nucleus pulposus acts allows the vertebral disc to withstand forces of compression and torsion, permitting the liquid exchange between capillaries and vertebral discs and the axis of vertical movement between two vertebrae. The fibrous annulus, on the other hand, participates in the stabilization and movement of the vertebral bodies and loads dampening. However, with aging, its biomechanical efficiency starts to decrease due to dehydration. The nucleus pulposus progressively loses its capacity to hold water and the annulus fibrosus begins to lose its elasticity, demonstrating the degradation of the nutrition mechanism and then resulting in disc degeneration. New studies show that the main factors influencing healthy and degenerated intervertebral disc are: mechanical load, genetic influences, diffusion of nutrients and oxygen through the intervertebral disc matrix.The search for chronic low back pain treatment is growing. In this study, we sought to assess the physical capacity of patients undergoing surgical treatment of the spine through the treadmill stress test. In addition to diagnosing cardiovascular diseases, the treadmill stress test also determines prognosis and assesses therapeutic responses to exercise tolerance, in addition to being a test considered to be of low risk. The patient is submitted to a programmed physical effort, which allows the assessment of their clinical, electrocardiographic, hemodynamic, metabolic, autonomic and ventilatory responses. The test will enable the evaluation of the therapeutic interventions results and the patient's actual physical conditions.The treatment of chronic low back pain, among its many causes, includes several therapeutic options, from conservative treatment to surgical intervention.The aim of this study was to assess whether the spine surgical approach for degenerative diseases can influence the physical capacity of patients, correlating it with cardiorespiratory function.This study was approved by the research ethics committee and (number 2.904.787/2018) was carried out in accordance with the 1995 Declaration of Helsinki in the period from May 2019 to May 2020. Nine patients of both genders, aged between eighteen and sixty years, scheduled for spinal surgery for degenerative disease in the lumbar segment were included.Patients with neuromuscular diseases, history of cardiovascular diseases, spine fractures, any sequelae on spine, pelvis and lower limbs diseases were excluded due to limitations in performing the treadmill stress test.A prospective study was carried out, with qualitative and quantitative data collection. Patients were submitted to the exercise test in two moments, which would be done fifteen days before the surgical procedure and sixty days after the surgery. For this purpose, a treadmill was used for thirty minutes, and vital signs such as blood pressure, respiratory and heart rate were measured.The test was performed by a cardiologist according to the Bruce protocol with a progressive increment in inclination and speed, to assess functional capacity.Data collection began after approval by the Research Ethics Committee and the signing of the free and informed consent form by the volunteers.A significance level of 0.05 (5%) was defined for this work. We chose to use non-parametric tests, as the dataset has a low sampling. Pre and post operative tests were compared using the Wilcoxon test, as the data are paired.Nine patients were included, 6 females and 3 males. The minimum age was 18 years and the maximum age was 62 years with an average of 45 years.All patients included had the degenerative condition of the lumbar spine as their underlying disease, and all underwent spinal arthrodesis with instrumentation of up to 3 levels.When evaluating the associated comorbidities, we considered as obesity patients those with a body mass index (BMI) above 35 and overweight BMI ranging from 28 to 34.9. The distribution of comorbidities was presented in When we analyzed the reason for the interruption of the test , we obse16,17,18 There was no difference regarding gender distribution, even with the prevalence of female with 66.7% and male with 33.3% . This prevalence of female gender was found in several literature review papers for chronic low back pain. The obesity was the most recurrent comorbidity in this study, with 44.4%, and it may be one of the variables with the most interference in the postoperative evaluation. Patients had an increase in body weight, which may be due to improved pain, mood, and reduced use of oral medications, which could lead to an improvement in gastrointestinal feelings. In several papers, obesity has been listed as an important factor in etiology and pain. One of these studies was carried out with an epidemiological profile of Brazil.This study evaluated the surgical approach in the treatment of degenerative disease of the spine, with a treadmill stress test performed in the preoperative and postoperative periods (3-month). The mean age of patients was 44.6 years, with a low variability, keeping the data homogeneous and in accordance with the previous literature.In the comparison pre and postoperative for the treadmill stress tests, our aim was to evaluate the patient's physiological changes after the surgery improvement in the low back pain and the limitation it could be causing. However, it was not significant between these two moments. No previous similar study was found in literature. The moments (pre- and postoperative) and the reasons of treadmill stress test interruption were evaluated. It was found that there is a statistical difference between the moments for the distribution of dyspnea, where the percentage raised from 0.0% in the preoperative period (p = 0.023) to more than 44% in the postoperative period, which led us to think that even with the improvement in pain and functional limitation, obesity may influence the dyspnea, since even some patients being smokers or former smokers, they did not present preoperative dyspnea. We did not find papers to make a comparison with the data obtained in our study.This study presents us with some questions and directs us to new variables to be observed in the surgical treatment of the spine, emphasizing the importance of metabolic disorders and obesity, for example, not only as triggering factors, but also as harmful factors in the intra and postoperative. Relevant information was given to patients, such as problems encountered in the postoperative period. Aiming to improve clinical conditions and quality of life, trained multidisciplinary professionals such as nutritionists, psychologists and physiotherapists were suggested. We can also think that dyspnea may not have been observed, as the mechanical disorder of chronic low back pain would not allow this patient to make great efforts, which may not allow an activity that would cause dyspnea. The removal of this factor associated with the time of postoperative convalescence could add another factor not analyzed. Perhaps the need for earlier and more intense rehabilitation after surgery, after removing the mechanical factor, could be the best option to improve this limiting clinical condition. Some limitations of our study must be presented – small sample and short follow-up - however, it could provide us with new possibilities for study, leading to future research.Improvement achieved with spinal surgery does not have a statistically significant in tiredness, pain, and fatigue in the lower limbs in patients with chronic low back pain.Regarding patients who were not able to complete the treadmill stress test due to physical limitations after surgery, this probably occur due to poor physical conditioning, being necessary to interrupt the test due to dyspnea.


This review was conducted to evaluate the efficacy and safety of N2O in patients undergoing puncture biopsy.Nitrous oxide  were included if they investigated the effect of N2O had better analgesic effect . In addition, N2O significantly alleviated patient anxiety  and improved patient satisfaction . There was no significant difference regrading the risk of nausea , headache , dizziness  or euphoria  between the N2O group and the control group.Twelve RCTs with 1070 patients were included in the qualitative review, of which eleven RCTs were included in the meta-analysis. Pooled analysis suggested that compared with the controls , N2O might be effective for pain management in patients undergoing puncture biopsy.The present review suggested that N Puncture biopsy is the main way to gain tumor tissue or cell sample for histopathological diagnosis , such as2O) is an inhalational agent with analgesic, sedative and anti-anxiety properties [2O regarding pain management in patients undergoing puncture biopsy and no consistent conclusion was made. Thus, we conducted a systematic review and meta-analysis of RCTs to assess the efficacy and safety of N2O in patients undergoing puncture biopsy.Nitrous oxide  Population: adults undergoing puncture biopsy; (2) Intervention: N2O inhalation; (3) Comparison: placebo or other analgesic methods; (4) Outcome: at least one of the following endpoints: pain score, anxiety score, patient satisfaction and side effects; (5) Design: randomized controlled trial.Relevant articles were identified by searching PubMed, Embase, the Cochrane Library, Web of Science, Scopus and the ClinicalTrials.gov  without language restriction. Electronic searches were conducted using the Exploded Medical Subject Headings and appropriate corresponding keywords: “nitrous oxide”, “Entonox”, “NTwo authors independently extracted the following data: first author, year of publication, country, number of patients, patient characteristics, interventions, controls, adjuvant analgesics and main outcomes. We would contact the original authors by e-mail if data needed clarification or were not presented in the article. Extracted data were checked by the third author and any dispute was settled by consultation.The primary outcome was pain score. Secondary outcomes included anxiety score, patient satisfaction and side effects. The pain score, anxiety score, and patient satisfaction were expressed using a visual analogue scale (VAS) or numeral rating scale (NRS) and was transformed to a 0–10 cm scale when the data were reported on a 0–100 mm scale. The data on the side effects were dichotomous. If the outcome data were not reported by mean±SD, they were converted according to the Cochran Handbook . The defTwo authors independently assessed risk of bias in the included RCTs with the method recommended by the Cochrane Collaboration . The qua2. If I2 was<50%, the studies were considered as homogeneous, and a fixed-effect model was used. If I2 was ≥50%, there was significant heterogeneity among the studies, and a random-effects model was used. Potential sources of heterogeneity were identified by sensitivity analysis conducted by omitting one study in each turn and investigating the influence of a single study on the overall pooled estimate. Prior subgroup analyses were conducted to explore the influence of type of puncture biopsy, different controls, and gender on the overall pooled estimate. Publication bias was appraised by visually examining a funnel plot. P < 0.05 was considered statistically significant.The statistical analysis was conducted using Review Manager software . Differences were shown as the risk ratio (RR) with 95% confidence interval (CI) for dichotomous outcomes, and the weighted mean difference (MD) with 95% CI for continuous outcomes. The heterogeneity between the studies was assessed using IThe overall search yielded 2229 citations, of which 2199 were weeded out for various reasons based on the title and abstract. The full texts of the remaining 30 publications were scrutinized for further assessment and then twelve RCTs  were eli2O group, air group and blank group, and the other trial [2O group, lidocaine group and blank group. One trial [2O with 1% lidocaine in transabdominal chorionic villus sampling. One trial [2O with midazolam in patients undergoing bone marrow biopsy. The remaining eight trials [2O with placebo . Sensitivity analyses were performed by omitting one study in each turn and did not significantly alter the heterogeneity . Subgroup analyses were conducted to examine the influence of type of puncture biopsy, different controls and gender on the pain score. The superiority of N2O for painful diagnostic procedure was significantly evident in patients receiving PLB [2 = 0%), LP [2 = 57%), and TUSPB [2 = 98%)  and in females’ [2O group was significantly lower than that in the placebo group [2 = 90%) and higher than that in the midazolam group [2O group and the lidocaine group [2 = 89%) , LP , 29  . Pooled n males’ , 23, 28 bo group , 24–29 (2 = 89%) .2O significantly relieved patient anxiety 2O compar2O in adults undergoing puncture biopsy. The accumulated evidence from the present study showed that N2O might be an effective way of analgesia and sedation, which relieved pain perception and anxiety in patients undergoing diagnostic painful procedures. Additionally, compared with other analgesic methods, N2O had no excessive side effects.To our best knowledge, this was the first systematic review and meta-analysis on the efficacy and safety of N2O in providing pain relief during bone marrow aspirate and trephine biopsy, midazolam caused respiratory depression, and care must be taken to monitor respiratory function which may prolong the length of hospital stay. Our pooled analysis indicated that compared with the controls, N2O had better analgesic effect with significant heterogeneity. The heterogeneity could be caused by several critical factors, such as the gender of patients, type of operation, control group, ratio of N2O/O2, inhalation time, the time point of data collection, and the number of puncture biopsies. Considering the limited number of studies included, the findings in the subgroup analyses should be evaluated rigorously and more high-quality RCTs are needed in the future.To date, puncture biopsy is still a crucial method for the identification and analysis of pathological tissue and cell morphology to help doctors to make the pathological diagnoses. Generally speaking, conventional puncture biopsy is conducted when the patient is conscious. Pain, fear and discomfort with regard to the puncture biopsy often reduce patient’s compliance, which may delay the timely diagnosis and treatment of the tumor. Nowadays, a common analgesia mode is local anesthesia with lidocaine  in minor2O was a self-administered inhaled gas reserved in a pre-prepared cylinder and trained nurses can conduct without the presence of professional anesthesiologists. Its action is rapid and reversible after stopping inhalation and N2O has no depressive effects on the respiratory or cardiovascular function [2O and 80% oxygen has an equivalent analgesic effect as well as a good sedative effect with 15 mg morphine [2O significantly reduced patients’ anxiety. Notably, Clark et al. [2O has amnesia characteristics so that patients often express an inability to recall severe pain or tension, even the entire procedure. In recent years, several studies have shown that N2O can be used in minor dental surgery, labor analgesia, pediatric operation pain , and trauma first aid [2O group and the control group. This finding may be related to the short inhalation time or low concentration of N2O. Most of the included studies applied 50% N2O/O2 inhalation 5 min before and during the biopsy, and the N2O/O2 inhalation was stopped at the end of the operation. In addditon, the frequency of side effects was relatively low among the included studies. Other side effects recorded in the included studies included oxygen desaturation (pulse oximetric saturation ≤94%), arterial hypotension, bradycardia, numbness and drowsiness, which usually disappeared rapidly after discontinuation [2O is a greenhouse gas and anesthesia is responsible for approximately 1% of N2O emissions in the atmosphere. Hence, N2O should be used by trained people and attention should be paid to scavenging it properly.Nfunction , and doemorphine . Three tmorphine , 29, 30 k et al.  reportedirst aid –46. As finuation . N2O is There were several limitations in the present study. Firstly, several included RCTs did not describe randomization and blinding in detail and the included trials were mostly single-blinded, which might affect the reliability of the pooled results. Secondly, the type of puncture biopsy and control groups varied among the included RCTs, which might lead to observed heterogeneity and thus impairing the robustness of our findings. Thirdly, several secondary outcomes and subgroup analysis only included not more than two RCTs, which need more large sample RCTs in the future so as to increase the reliability of the results. Fourthly, the outcome data in several included RCTs were not expressed as mean±SD. The measurement tools and time point of data collection also varied in the included studies. The data conversion and standardization were conducted in the pooled analysis, which might impair the robustness of the results. Finally, pain and anxiety perception were subjective outcomes and were not likely to be consistently assessed by individual patients.2O might provide a better analgesic effect and slight side effects for puncture biopsy. However, due to the poor overall quality of the included studies and limited evidence, more well-designed randomized controlled trials are still needed to confirm our findings in the future.In summary, the present systematic review and meta-analysis suggested that the use of NS1 Checklist(DOCX)Click here for additional data file.S1 Table(DOCX)Click here for additional data file.S1 Fig(TIF)Click here for additional data file.S2 Fig(TIF)Click here for additional data file.S3 Fig(TIF)Click here for additional data file.S4 Fig(TIF)Click here for additional data file.S5 Fig(TIF)Click here for additional data file.S6 Fig(TIF)Click here for additional data file.S7 Fig(TIF)Click here for additional data file.


Chronic pelvic inflammatory disease (CPID) is a clinically common gynecological disease. Patients experience chronic pelvic pain and often accompany with emotional dysfunction. However, the impact and correlation of anxiety and depression on pain sensitization is not completely known.  To explore the differences and correlations among anxiety, depression, and pressure pain threshold (PPT) of acupoints in patients with CPID.  One hundred and forty-seven patients with CPID were recruited. The Visual Analog Scale (VAS) and short-form McGill Pain Questionnaire (SF-MPQ) were used to assess pain. Self-Rating Anxiety Scale (SAS) and Self-Rating Depression Scale (SDS) were used to evaluate the emotional state of patients. The PPT of acupoints was collected using an electronic Von Frey by two licensed acupuncturists. P < 0.05). In addition, significant differences were observed in the PPTs of ST28 (R), ST29 (R), SP10 (R), SP9 (R), SP9 (L), ST36 (R), and LR3 (L) between the two groups (P < 0.05). No considerable differences in PPTs at the other acupoints were observed between the two groups. SAS scores showed a positive correlation with PPTs of ST29 (R), SP10 (R), SP9 (L), ST36 (R), and LR3 (L). No remarkable correlation was observed between the SDS scores and PPTs.  The CPID patients were divided into anxiety-depression group (group A) or nonanxiety-depression group (group B), according to the SAS and SDS scores. Finally, there were 73 patients in group A and 74 patients in group B. Group A had significantly higher SAS, SDS, VAS, and SF-MPQ scores than group B (ChiCTR2100052632. Anxiety and depression can affect the PPT of some acupoints in CPID patients, which may provide a reference for acupoint selection for acupuncture treatment of CPID with emotional disorders. This trial is registered with  Pelvic inflammatory disease (PID) is an inflammatory disorder of the female upper genital tract , with a wide range of clinical manifestations , 2. The Most CPID patients have symptoms of chronic pelvic pain, because of the continuous effects of inflammation. A study demonstrated that chronic pelvic pain after an acute episode of PID was common and associated with decreased physical and mental health . PsycholThe pressure pain threshold (PPT) is a semiobjective method used to measure pain , 13, whiThe CPID patients were recruited from the outpatient department of the Affiliated Hospital of Chengdu University of Traditional Chinese Medicine (CDUTCM) from March 2021 to September 2022. All patients were diagnosed by clinicians in the Gynecology Department of the Affiliated Hospital of CDUTCM.ChiCTR2100052632). All the subjects signed the informed consent.The study was performed according to the principles of the Declaration of Helsinki, approved by the Ethics Committee of the Affiliated Hospital of CDUTCM (NO. 2021KL-014), and registered at the Clinical Trial Registry (registration number: Patients were enrolled if they fulfilled the following criteria: 1) diagnosed with pelvic inflammatory disease , 20; (2) diagnosePatients with any of the following conditions were excluded: (1) if in critical condition at acute stage; (2) if pregnant or lactating; (3) if complicated by malignant tumors or serious diseases of heart, brain, liver, kidney, urinary, digestive, or reproductive system; and (4) if had unclear conscious and unable to cooperate with the investigator to complete the study.Baseline data consisted of age, body mass index (BMI), duration of disease, education, and resting blood pressure. The Self-Rating Anxiety Scale (SAS)  and SelfPPT data (g) were collected using an electronic Von Frey  to apply pressure at a constant speed on acupoints. The acupuncturist held the detector and moved the probe tip vertically downward the skin at an even speed. The probe tip was immediately removed once the patients felt a sensation of pain and recorded the number on the detector as PPT . All theIn accordance with the results of literature data-mining  and expeThe eligible patients completed the questionnaire survey and PPT test. Relevant data, including demographic information, SAS, SDS, VAS, and SF-MPQ scores, were independently collected by blinded evaluators. The PPT data were collected by another two blinded licensed acupuncturists.n%) and compared using the χ2 or Fisher's exact test. Normally distributed quantitative variables using t-test were expressed as mean (M) ± standard deviation (SD). Skewed quantitative variables were analyzed by the Mann–Whitney U test, expressed as median (IQR). Spearman correlation coefficient was employed for nonnormal distribution data for correlation analysis. P value <0.05 was considered statistically significant.The SPSS version 26.0 software was used for statistical analysis by the blinded evaluator. Categorical data were described as number and percentages . Otherwise, if the SAS score was less than 45 and SDS score was less than 50, the patients were assigned to nonanxiety-depression group (group B). Finally, there were 73 patients in group A and 74 patients in group B.P > 0.05; The baseline data included age, BMI, education level, resting blood pressure, and duration of illness. Except for duration of illness, no remarkable differences in baseline data were found between the two groups  and SDS scores  vs. 40 ; Z = −7.721, P < 0.05). Significant difference in VAS scores  was found between the two groups. In addition, the SF-MPQ scores in the group A were also greater than group B  vs. 10.25 ; Z = −3.960, P < 0.05; Compared with group B, the group A had significantly higher SAS scores  vs. 38.5 ; P < 0.05). No considerable differences in PPTs at the other acupoints were observed between the two groups , ST29 (R), SP10 (R), SP9 (R), SP9 (L), ST36 (R), and LR3 (L) in group A were higher than that in group B (P > 0.05). However, in the total sample size, SAS scores positively correlated with PPTs of ST29 (R), SP10 (R), SP9 (L), ST36 (R), and LR3 (L) (P < 0.05). No remarkable correlation was observed between the SAS scores and PPTs of ST28 (R) and SP9 (R). For SDS, the results of the correlation were similar for those in the group A  out of 147 CPID patients had emotional disorders, and previous study also found that 37 (51%) out of 72 patients with pelvic pain were clinically depressed . BesidesAnxiety and depression are common comorbidities in patients with inflammatory diseases –38, and Central and local peripheral sensitization occurs when the body experiences inflammation or pain, causing patients to become more sensitive to pain stimulation. Local hyperalgesia may be caused by peripheral nervous system changes due to prolonged inflammatory processes, and hyperalgesia remote to the area of pain indicate the involvement of the central nervous system. These central changes are associated with ongoing pathological neuronal signals from the painful area . TherefoPPT is a widely used method for measuring pain sensitization. Numerous studies have indicated that patients who experienced chronic pain had significantly lower PPTs compared with healthy controls –48. In aPPT is also used to measure acupoint sensitization; traditional Chinese medicine believes that the state of acupoints is dynamic and PPT of acupoints changes with the disease. For instance, some studies indicated that lower PPT was observed at the sensitized acupoints in the patients with disease , 53, andIn the current study, the PPT of six acupoints including ST28, ST29, ST36, SP10, SP9, and LR3 were different between the two groups. These acupoints belong to the stomach meridian, spleen meridian, and liver meridian, respectively. Traditional Chinese medicine believes that emotion is closely related to the liver, involves the spleen and stomach. Dysfunction of the liver is frequently accompanied by emotional changes such as depression or anxiety. When the liver qi is too strong, it will affect the spleen and stomach. The acupoints of the liver, spleen, and stomach meridians are usually selected when applying acupuncture to treat emotional disorders in clinical, and the results of this study have provided evidence for these acupoint selection principles. Besides, differences in the PPT of the acupoints between the two groups meant that these acupoints were sensitized by emotion. Previous study showed that intervention at sensitive acupoints is effective in relieving disease symptoms . TherefoAs for the correlation analysis, in the group A, there were no remarkable correlation between the SAS, SDS scores, and PPTs of all the acupoints. But in the total sample size, SAS scores positively correlated with PPTs of ST29 (R), SP10 (R), SP9 (L), ST36 (R), and LR3 (L). The discrepancy in findings may be attributed to sample size and the degree of emotional disorder. When group A was analyzed separately, the sample size was too small to reflect the results of correlation. In a study with 34 juvenile fibromyalgia patients and 31 controls, no relationships were observed between anxiety and pressure pain . AnotherIn summary, anxiety and depression should be actively concerned in patients with CPID and treated appropriately. If treatment is not timely, it may become an obstacle to alleviation of the pain. Anxiety and depression affected the PPT of some acupoints in CPID patients, which may cause pain sensitization. Acupuncture at ST28, ST29, ST36, SP10, SP9, and LR3 may be an appropriate treatment for anxiety and depression in patients with CPID.There were some limitations in this study. First, only the acupoints were detected, the PPT of pain points remains to be further explored. Second, the sample size was relatively small. Third, different anatomical locations may have different sensations; only one method of PPT measurements was applied in this study, and other instruments may be used in different areas to measure the pain sensitization for more accurate results in the future.The findings of this study suggest that anxiety and depression can affect the PPT of some acupoints in CPID patients, and these acupoints may be used as stimulation points for acupuncture to treat CPID with emotional disorders.


Background: Vulvodynia is defined as a chronic idiopathic vulvar pain condition. This study aimed to investigate the effect of central sensitization on the prognosis of neuromodulator treatment for vulvodynia. Method: A total of 105 patients with vulvodynia who underwent pelvic mapping pain exploration were included and scored according to the Convergence PP Criteria for pelvic pain and central sensitization. The patients were treated according to chronic pelvic pain guidelines, and their response to treatment was evaluated. Results: A total of 35 out 105 patients (33%) with vulvodynia had central sensitization, which was associated with comorbidities, dyspareunia, pain with micturition, and pain with defecation. Dyspareunia and pain with defecation were independent prognostic factors for central sensitization. Patients with central sensitization experienced more pain during intercourse, urination, or defecation, had more comorbidities, and responded worse to treatment. They required more treatment, with a longer response time (over 2 months). Patients with localized vulvodynia were treated with physiotherapy and lidocaine, while patients with generalized vulvodynia were treated with neuromodulators. Amitriptyline was effective in treating patients with generalized spontaneous vulvodynia and dyspareunia. Conclusions: Overall, this study highlights the importance of considering central sensitization in the diagnosis and treatment of vulvodynia and the need for individualized treatment based on the patient’s symptoms and underlying mechanisms. Vulvodynia patients with central sensitization had more pain during intercourse, urination, or defecation, and responded worse to treatment, requiring more time and medication. Vulvodynia is a chronic idiopathic vulvar pain lasting at least 3 months, firstly introduced as a separate entity from vulvar pain syndrome in 2015 by the International Society for the Study of Vulvovaginal Disease (ISSVD) [It is the most common cause of pain during sexual intercourse in postmenopausal women . The prep and calcitonin related peptide, in the area innervated by the primary afferent nociceptors. This has been demonstrated to happen in some of the comorbid diseases to vulvodynia . Peripheral sensitization can be the beginning of central sensitization, when pain persists after the resolution of the cause. This may be because of substance p and calcitonin gene-related peptide (CGRP) and the increased reactivity of N-methyl-D-aspartate (NMDA) and amino-3-hydroxy-5-methyl-4-isoxazole propionate (AMPA) receptors increasing the signals received by the central nervous system, leading to hyperalgesia and allodynia. Thus, pain is uncoupled from the noxious stimulus, and normal inputs evoke exaggerated responses [The coexistence of symptoms of neuropathic pain , pain with or after micturition and/or defecation, variability in the distribution or intensity of pain, comorbidities, and trigger point pain in the pelvic floor musculature may be suggestive of central sensitization . Centralesponses ,11.Vulvodynia is understudied, due both to the complexity of generalized pain disorders as a whole and the hesitance of patients to share their symptoms to clinicians because of the stigma behind female pain . FurtherThe aim of this study was to evaluate the response to commonly used treatments in vulvodynia, including physiotherapy, topical lidocaine, intravaginal diazepam, antidepressants, anticonvulsants, and minimally invasive neuromodulation, and compare the outcomes between patients with and without central sensitization. The study also aimed to examine the demographic and treatment disparities among patients with generalized and localized vulvodynia, as well as those with and without central sensitization. Finally, the study further sought to ascertain whether central sensitization exacerbates or delays treatment response and its prognostic value for vulvodynia, as well as to explore whether the type and characteristics of vulvodynia impact the prescribed and successful treatment approaches.The medical records of 393 consecutive female patients with chronic pelvic and perineal pain syndrome who sought consultation at the Puerta de Hierro Majadahonda University Hospital in Madrid, Spain, from May 2018 to July 2022 were reviewed. Ethical approval for this study was granted by the Puerta de Hierro Majadahonda University Hospital Institutional Review Board. a.Localized: vestibulodynia , clitoridynia (pain in clitoris); generalized; or mixed .b.Provoked: insertional, contact; spontaneous (no contact); or mixed (provoked and spontaneous).c.Onset: primary  or secondary . d.Temporal pattern: intermittent, persistent (if symptoms have lasted more than 3 months and persist), constant, immediate , delayed (symptoms appear later).The main inclusion criteria were female patients with chronic pelvic and perineal pain syndrome that had been experiencing vulvar, vestibular, vaginal, clitoral, and/or perineal pain for at least three months diagnosed with vulvodynia . AccordiThe exclusion criteria referred to patients with pain in a location other than those indicated above, with a symptom onset below 3 months, a diagnosis of any type of known-cause vulvar pain , patients with no programmed follow-up consultations, patients with no prescribed treatment, or patients with incomplete data. The data assessed included age on first consultation, complete medical history , pain location , old obstetric scar), duration of pain (estimated by the patient as the number of years between the onset of symptoms and the date of first consultation), comorbidities, dyspareunia, type of vulvodynia , result on the Convergences PP Criteria Score, treatment before consultation, treatment prescribed after consultation, number of physiotherapy sessions, and subjective response to prescribed treatment .The comorbidities were selected according to Yunus et al. , relatedThe Convergence PP Criteria Score was developed by Levesque et al.  as cliniThe examination was performed by a single physician with expertise in chronic pelvic pain and data from the examination were collected based on the pain-mapping method reported by Pereira et al. , includiCotton swab testing of the S2–S4 dermatome and vestibule: the absence of signs and symptoms during the physical examination confirms the integrity of the C fibers.Clitoris, bulbospongiosus, and perineal reflexes: an evaluation of the motor response of the terminal branches of the pudendal nerve is conducted by gently touching the labium minus lateral to the clitoris, the perineum, and the clitoris with a cotton swab, and the normal motor activity at S2–S4 is indicated by anal sphincter contraction.Tinel’s sign in the sciatic spine area: to evaluate the third segment of the pudendal nerve, pain is reproduced with transrectal compression of the third segment of the PN (Tinel sign) in the sciatic spine and Alcock’s canal.Tinel’s sign at the clitoris: to evaluate the dorsal nerve of the clitoris, the clitoris is compressed to locate painful spots.Bilateral palpation in order to identify painful spots—retropubic, ischiopubic ramus, ischium, sacrospinous ligament, sacrum, and coccyx area. Bilateral mobility of the hip and lower extremities is explored .Levator ani muscle (LAM): assessment of painful palpation of the pubococcygeus muscle.Obturator internus muscle (OIM): contracture of the OIM with flexion and external rotation of the hip in the supine decubitus position and transgluteal examination of OIM segments—pelvic (ischium), medium (midpoint between trochanter and coccyx), and gluteal (hip).Piriformis muscle (PM): simultaneous hip external rotation and abdominal flexion is encouraged to reproduce the pain. PM is palpated transgluteally five centimeters above the OIM middle segment.Patients were asked to rate their level of pain on a scale from 0 (no pain) to 10 (worst pain ever experienced) during the assessment.The patients in this study were treated according to the recommendations on the National Guideline Clearinghouse for pharmacological management of neuropathic pain and recent vulvodynia studies. The first step of treatment involved dietary recommendations, topical medications , physiotherapy, and psychological therapy . If thes▪Pelvic floor physiotherapy, including 30–40 min of intravaginal and external perineal massage , thermotherapy, and biofeedback techniques such as the use of vibrators and vaginal dilators to use during the session and at home. If lack of response or partial response to the described techniques was experienced, transcutaneous electrical nerve stimulation (TENS) was used 2 times a week for 20 min each session, and the electrodes were applied to the labia majora in a V-shape.▪Topical lidocaine .▪Vaginal diazepam .Patients with provoked vulvodynia could be prescribed:▪Neuromodulators such as tricyclic depressants  and serotonin and noradrenaline reuptake inhibitors .▪Anticonvulsants .▪Minimally invasive neuromodulation (MIN) techniques  of sacral roots and pudendal nerve).Patients with spontaneous vulvodynia could be prescribed:▪Psychological therapy  for treatment of stress and the response to pain when a psychological component to pain was identified.▪Hygienic–dietary and behavioral measures, such as vulvar hygiene, lubrication, and use of vaginal dilators.All types of vulvodynia could be prescribed:▪Topical estradiol creams for menopausal women.▪Ospemifene (60 mg/24 h).Patients with vaginal atrophy could be prescribed:In the follow-up consultation, the response to treatment was evaluated using the patient’s subjective relief of symptoms as a percentage, using a subjective pain evaluation scales (EVA). A relief of symptoms greater than 30% was considered a response to the prescribed treatment. This was done in order to exclude the possibility of a placebo effect. p ≤ 0.05 was considered statistically significant. Descriptive analysis was carried out to evaluate the cohort. Dichotomous or categorical variables were expressed as absolute values and percentages; continuous variables were expressed as the mean and median. The Chi-square test was used to estimate the relationship between variables and pain. The relative risk (RR) was calculated. Differences in distributions of dichotomous variables were analyzed using Fisher’s exact test. Differences in distributions of continuous variables were analyzed using the Kruskal–Wallis test. A value of p < 0.1 entered a multivariate study by performing a Cox logistic regression to determine if central sensitization was an independent prognostic factor [Kaplan–Meier curves were used to compare treatment efficacy and treatment time, to determine the number needed to treat, number of patients who must be treated to obtain cure of their disease, and to evaluate the response to neuromodulator treatment between patients with central sensitization and patients without central sensitization . Subsequc factor . The staWe identified 393 medical records in our hospital’s electronic database of female patients who sought consultation between May 2018 and July 2022. After excluding 288 cases that had missing data needed for the study or met exclusion criteria, a total of 105 patients met all inclusion criteria and were selected for evaluation.Demographic characteristics of patients are shown in Of the 105 patients analyzed, 35 (33.3%) fulfilled five or more of the Convergence PP Criteria, this being the point suggested by Levesque et al. to consider central sensitization. A total of 40% of patients had any of the comorbidities described above, 91.4% had dyspareunia, 37.1% pain with defecation, and 77.1% pain with micturition. The mean score obtained on the PP score among patients with no central sensitization was 4.1, which remained low for patients who developed central sensitization (5.6 points). Results are shown on The muscular distribution of pain in vulvodynia is in the LEA, OIM, and PM muscles . In our A number of 80 patients attended a follow-up consultation, from which a subjective relief to pain was recorded. The mean follow-up for these patients was 248.6 days (range 0–1449). Our results have revealed improvements in 63.8% of patients who attended a follow-up consultation. The response to the prescribed treatments according to the type of vulvodynia was as follows: generalized and spontaneous vulvodynia displayed 66.5% response; localized and provoked vulvodynia, 78.9%; localized and spontaneous vulvodynia, 73.6%; and generalized and provoked vulvodynia, 63.1%. All results according to the administered treatment are detailed in p = 0.006), dyspareunia (p = 0.004), pain with defecation (p < 0.001), pain with micturition (p < 0.001), and treatment (p = 0.018). However, logistic regression analysis revealed that pain with defecation (p = 0.010) and dyspareunia (p = 0.028) were the only independent prognostic factors for the development of central sensitization; results are shown in This study highlighted demographic differences among different patient groups. Univariate analysis also found that central sensitization (PP score > 5), was correlated with various factors, including comorbidities (p < 0.001), pain location (p < 0.001), dyspareunia (p = 0.028), pain with defecation (p = 0.012), and pain in pelvic trigger points (p = 0.065). However, only the latter was found statistically significant (p = 0.006) in the multivariate analysis, as shown in Among different types of vulvodynia, the univariate analysis found significant differences in relation to age , and in the PP criteria score between patients with a duration of symptoms larger and lower than 2 years (p = 0.021); results are shown in p = 0.024). Additionally, the study also found significant associations between quantitative variables, such as age and type of vulvodynia (p = 0.04). However, there was no significant difference in response to treatment between those groups in patients with central sensitization (p = 0.631). Patients with central sensitization were prescribed more lidocaine, minimally invasive neuromodulator treatments, and psychological therapy, as shown in Furthermore, this study analyzed treatment responses and found that patients without central sensitization responded more frequently to treatment for provoked vulvodynia (76.5%) than for spontaneous vulvodynia (64.7%) (p = 0.073). The results of this analysis are shown in p = 0.009).Finally, Kaplan–Meier curves showed that patients with central sensitization took longer to respond to treatment than those without central sensitization , but the difference was not statistically significant , and between age and type of vulvodynia (p < 0.001), with multifocal pain being the most common presentation (p < 0.001). Specifically, younger patients were more likely to have localized provoked vulvodynia, while patients with spontaneous generalized vulvodynia tended to be older, with a difference of 17 years.Patients with central sensitization tended to be older, with a mean age of 43.5 years at their first consultation. Significant differences were observed between age groups and pain location (p = 0.021), with a weak direct correlation between the score and symptom duration demonstrated (p = 0.024). Furthermore, significant variations in PP score were observed when symptom duration exceeded 2 years (p = 0.021).Patients with central sensitization tended to have a longer duration of symptoms . In our study, there was also a difference in the PP criteria score between patients with lower (score of 3.8) and higher (score of 5) symptom duration  reported a significant improvement in their symptoms. However, the response to treatment was influenced by two significant factors described above: the presence of central sensitization of pain and the type of vulvodynia.p = 0.053). Additionally, there was an inverse correlation between the PP score and response to treatment (p = 0.009), indicating that patients with higher scores had a lower response to treatment. Conversely, the PP score showed a direct correlation with the duration of symptoms.Patients with central sensitization had a lower response rate to treatment compared to others and required three times more treatment than patients without central sensitization (p = 0.052). Patients without central sensitization responded more frequently to treatment for provoked vulvodynia (76.5%) than for spontaneous vulvodynia (64.7%). However, there was no significant difference in response to treatment between patients with provoked or spontaneous vulvodynia who had central sensitization (p = 0.631).With regard to the type of vulvodynia, patients with generalized vulvodynia had a lower response rate to treatment (65.7%) compared to patients with localized vulvodynia (76.6%) (p = 0.05), minimally invasive neuromodulation (p = 0.007), and psychological therapy (p = 0.015).Around 60% of patients with central sensitization were treated with amitriptyline, particularly those with GSV and dyspareunia. Other frequently prescribed agents were topical lidocaine  compared to patients with vulvodynia but no central sensitization; the time period for response to treatment was set at more than 2 months, and the number of patients needed to treat when having comorbidities or dyspareunia was 3.3, with pain related to micturition at 1.6, and with defecation at 2.4.Despite the many unknown aspects of vulvodynia, its importance should not be underestimated. Recent studies have shown that it significantly affects quality of life, including the ability to perform basic activities and experience sexual satisfaction . Some stWhile this study provides valuable insights into the demographic, clinical characteristics, and treatment of patients with vulvodynia, its small sample size and lack of diversity may limit the generalizability of the findings. As it is a study based on cohorts, there are limitations when studying rare illnesses, which is the case for vulvodynia, which is rarely reported by patients . MoreovePrescribed treatments for patients with vulvodynia  were multidisciplinary in nature, combining several treatments simultaneously. The prescribed treatments had a response rate of 60.9% for patients with central sensitization, which was lower compared to patients without central sensitization (72.7%). The most frequently used medications for patients with central sensitization were diazepam (37.5%), amitriptyline (40.3%), lidocaine (42.5%), anticonvulsants (42.9%), MIN (51.5%), along with physiotherapy (33.3%) and psychological therapy (58.8%). Furthermore, central sensitization delayed the treatment response, and patients required more treatment, with a longer response time (over 2 months). Patients with vulvodynia and central sensitization experienced more pain during intercourse, urination, and defecation, and they had a higher prevalence of comorbidities. Dyspareunia and proctalgia were independent prognostic factors for central sensitization. In terms of the type of vulvodynia, patients with generalized vulvodynia had a lower treatment response rate compared to patients with localized vulvodynia, and those without central sensitization responded more frequently to treatment for provoked vulvodynia than spontaneous vulvodynia. However, the small sample size, the lack of a control group, and the lack of diversity in the study may limit the generalizability of the findings.