Neuropathic pain is a common complication in neuromyelitis optica spectrum disorder (NMOSD), which seriously affects the quality of life of NMOSD patients, with no satisfactory treatment. And risk factors of neuropathic pain are still uncertain.To investigate the risk factors of neuropathic pain in a NMOSD cohort.Our study was a retrospective case-cohort study, the patients diagnosed with NMOSD in the Department of Neurology from the Second Affiliated Hospital of Guangzhou University of Chinese Medicine from January 2011 to October 2021 were screened. Inclusion criteria were: (1) patients diagnosed as NMOSD according to the International Panel for NMO Diagnosis (IPND) criteria, (2) the aquaporin-4 immunoglobulin G antibodies (AQP4-IgG) test was performed. Patients without AQP4-IgG antibody were excluded. Clinical data, including sex, age of the first onset, symptoms of the first episode including neuropathic pain and attack types, localization of lesions of the first episode on Magnetic Resonance Imaging (MRI), Extended disability status Scale (EDSS) of the first onset, treatment of immunosuppression in the first acute phase, disease modifying therapy (DMT), treatment of neuropathic pain and APQ4-IgG status were collected from the hospital system database. Neuropathic pain was defined according to the International Association for the Study of Pain criteria and was described as “pain arising as a direct consequence of a lesion or disease affecting the somatosensory system”.P = 0.038) and age (OR 1.35 (1–1.81) P = 0.050) were independently associated with neuropathic pain among NMOSD patients and that gender (OR 12.11 (0.97–151.64) P = 0.053) might be associated with neuropathic pain among NMOSD patients.One hundred nineteen patients were screened and finally 86 patients fulfilling the inclusion and exclusion criteria were enrolled in our study. The prevalence of neuropathic pain in patients with NMOSD was 43.0%. Univariate analysis showed that the factors associated with neuropathic pain were the age at the onset, the attack type of optic neuritis, the attack type of myelitis, length of spinal cord involvement, localization of thoracic lesion, optic lesion, upper thoracic lesions, lower thoracic lesions, extended spinal cord lesions , extended thoracic lesions (≥ 4 thoracic lesions), intravenous immunoglobulin and mycophenolate mofetil. Multivariate regression analysis showed that extended thoracic lesions , age and gender might be independent risk factors of neuropathic pain among patients with NMOSD. However, with a small sample size and predominantly female, caution must be applied and these results need validating in further cohorts. Neuromyelitis optica spectrum disorder (NMOSD) is a relapsing inflammatory central nervous system disorder mainly involving the optic nerve and spinal cord. Except for the high recurrence rate and disability rate , 2, painSeveral clinical observations suggested that some factors such age, myelitis and mood were associated with NP in patients with NMOSD , 12, 13.Our study was a retrospective case-cohort study, the patients diagnosed with NMOSD in the Department of Neurology from the Second Affiliated Hospital of Guangzhou University of Chinese Medicine from January 2011 to October 2021 were screened. Inclusion criteria were (1) patients diagnosed as NMOSD according to the International Panel for NMO Diagnosis (IPND) criteria , (2) theP value less than 0.1 were included in a multivariate logistic regression model to assess the independent risk factors of neuropathic pain among NMOSD patients. The cut-off for statistical significance was P value less than 0.05.The dichotomous data were reported as the number with percentage, and the continuous data were expressed as the mean and standard deviation. The categorical variables were analyzed with a chi-square test. The continuous variables with normal distribution were analyzed using an independent two-sample Student’s t-test and data that were not normally distributed were analyzed with a nonparametric test. The variables that were statistically significant in the univariate analysis at Totally, 119 patients with NMOSD were screened. After the exclusion of 33 patients without AQP4-IgG antibody information, 86 patients were enrolled in this study . The mean EDSS of patients in NP and non-NP group was separately 4.5 ± 2.6 and 4.0 ± 2.8 (P = 0.435). The mean length of spinal cord involvement of patients with NP was longer than patients in non-NP group (5.8 ± 5.0 VS 3.0 ± 3.8) . 32 (86.5%) patients with NP had myelitis while only 31(63.3%) patients in non-NP group had myelitis during the first episode of the disease . 7(18.9%) and 20(40.8%) patients in NP group and non-NP group had optic neuritis . About the localization of the lesions, the percentage of the patients with cervical lesions was similar between two groups. There were more patients with thoracic lesion in NP group (61.8%) than non-NP group (36.4%). 1 (2.9%) patient in NP group and 7 patients (21.2%) in non-NP group had optic lesions (P = 0.047). The proportion of patients with upper thoracic lesions in the NP group was higher than in the non-NP group (52.9% VS 27.3%) . The percentage of patients with lower thoracic lesions in the NP group was higher than in the non-NP group (38.2% VS 15.2%) . The proportion of patients with extended thoracic lesions (≥ 4 thoracic lesions) in the NP group was higher than in the non-NP group (44.1% VS 9.1%) . Among the patients with myelitis lesions, the proportion of patients with extended spinal cord lesions  in the NP group was higher than in the non-NP group (76.5% VS 42.4%) . Among them, more patients with neuropathic pain use intravenous immunoglobulin in the acute phase , and more patients with neuropathic pain used mycophenolate mofetil during remission . In terms of pain treatment, 13.5% of patients with neuropathic pain did not use analgesics, 86.5% used antiepileptic drugs, and 24.3% used antidepressants  patients had neuropathic pain. The mean age of the first onset in the NP group was higher than in the non-NP group (51.2 ± 13.3 years VS 42.5 ± 13.2 years)  after adjusting for age, gender, optic neuritis, upper thoracic lesions, intravenous immunoglobulin, MMF and EDSS. Meanwhile, age was an independent risk factor of neuropathic pain in NMOSD patients (OR 1.35 (1–1.81) P = 0.050). Gender might be also an independent risk factor of neuropathic pain in NMOSD patients (OR 12.11 (0.97–151.64) P = 0.053)  were independent risk factors of neuropathic pain in NMOSD patients  were independent risk factors of neuropathic pain in NMOSD patients which were not reported in the previous studies. Patients with extended thoracic lesions had a 20.21-fold higher risk of neuropathic pain. Furthermore, age and gender might be also associated with neuropathic pain.The prevalence of neuropathic pain in patients with NMOSD was 31.5-85.5% , 12, 17.About the mechanism of neuropathic pain, the possible hypothesis was that neurons with bilateral descending projections to the lumbosacral superficial dorsal horn were concentrated in the autonomic intermediomedial nucleus surrounding the central canal of the upper/mid-thoracic spinal cord, and lesions of the upper/mid-thoracic segment may accompany pain easily .P = 0.024), especially the upper 6 thoracic segments  was associated with pain among NMOSD patients, and that pain score was higher in patients with than in those without extended spinal cord lesions   [P = 0.03) predicts greater myelitis-associated chronic pain than the presence of cervical lesions  [P = 0.422) [On the basis of this hypothesis, some studies began to investigate the relationship between neuropathic pain of NMOSD patients and the spinal cord. Several studies found that the number of involved spinal segments  . In Oxfo = 0.04) . On the However, these studies suggested the number of involved spinal segments especially the upper 6 thoracic segment or the presence of thoracic lesions or extended spinal cord lesions  might be associated with pain among NMOSD patients while our study pointed out the extended thoracic lesions(≥ 4 thoracic cord lesions) was an independent risk factor of neuropathic pain among patients with NMOSD which was the novelty of the present paper. Since the association between neuropathic pain and the features of spinal lesions is still controversial, prospective cohort studies were needed.In this study, gender might be also an independent risk factor of neuropathic pain in NMOSD patients which was not found in the previous studies , 20. FemP = 0.006). The multivariate analysis showed that age might increase the incidence of NP among NMOSD patients (OR 1.35 (1–1.81) P = 0.050).The correlation of neuropathic pain and age might be related to decreased small fibers and a declined neural plasticity , 28. PreUntil now, there were several hypotheses about the mechanism of neuropathic pain related with AQP4-IgG antibody status among NMOSD patients.Firstly, under physiological conditions, AQP4 is co-expressed with the excitatory amino acid transporter 2, which enables glutamate uptake by astrocytes . GlutamiSecondly, extensive loss of AQP4 could induce reactive astrocytes. A2 astrocytes secrete neuroprotective factors that promote neuronal survival, and then may inhibit the progression of chronic pain. A1 astrocytes not only secrete toxic factors that rapidly kill mature oligodendrocytes and neurons but also produce small molecules such as cytokines, chemokines and growth factors that influence the glutamine-glutamate-GABA axis –33.Therefore, the reactive astrocyte played an important role in the development of neuropathic pain among NMOSD patients.P = 0.082) [P = 0.174). Whether the neuropathic pain was associated with AQP4-IgG antibody status needed more studies to verify.Some clinical studies found that patients had neuropathic pain were tended to be AQP4-IgG-positive than those without pain  . In our As a retrospective study, the pain score of patients at the onset was not assessed. Therefore, we could not find out whether extended thoracic lesions were associated with the severeness of neuropathic pain. Further prospective studies with a more detailed evaluation of neuropathic pain were needed to verify our conclusion.Extended thoracic lesions (≥ 4 thoracic lesions), age and gender might be independent risk factors of neuropathic pain among patients with NMOSD. However, with a small sample size and predominantly female, caution must be applied and these results need validating in further cohorts.


The impact of long-term dizziness is considerable both on the personal level and in society and may lead to self-imposed restrictions in daily activities and social relations due to fear of triggering the symptoms. Musculoskeletal complaints seem to be common in persons with dizziness, but studies addressing these complaints as a widespread occurrence, are scarce. This study aimed to examine the occurrence of widespread pain in patients with long-term dizziness and investigate the associations between pain and dizziness symptoms. Further, to explore whether diagnostic belonging is related to the occurrence of pain.This cross-sectional study was conducted in an otorhinolaryngology clinic and included 150 patients with persistent dizziness. The patients were categorized into three groups: episodic vestibular syndromes, chronic vestibular syndromes, and non-vestibular group. The patients completed questionnaires on dizziness symptoms, catastrophic thinking, and musculoskeletal pain when entering the study. Descriptive statistics were used to describe the population, and associations between pain and dizziness were investigated by linear regression.Pain was reported by 94.5% of the patients. A significantly higher prevalence of pain was reported in all the ten pain sites examined compared to the general population. Number of pain sites and pain intensity were associated with the dizziness severity. Number of pain sites was also associated with dizziness-related handicap, but not with catastrophic thinking. There was no association between pain intensity and dizziness-related handicap or catastrophic thinking. Pain was equally distributed in the diagnostic groups.Patients with long-term dizziness have a considerably higher prevalence of pain and number of pain sites than the general population. Pain co-exists with dizziness and is associated with dizziness severity. These findings may indicate that pain should be systematically assessed and treated in patients with persisting dizziness.The online version contains supplementary material available at 10.1186/s12891-023-06279-z. Dizziness is a common complaint in the general population, with an estimated lifetime prevalence of 15 – 35% , 5. PhysMusculoskeletal complaints are common, also among patients with dizziness –12, but Studies that systematically examine musculoskeletal pain in patients with dizziness are scarce. Thus, the present study aimed to examine the prevalence, intensity and, distribution of musculoskeletal pain in patients presenting with persistent dizziness in an otorhinolaryngology clinic. Further, we wanted to investigate possible associations between dizziness symptoms and musculoskeletal pain.A cross-sectional study investigating pain in patients with long-term dizziness was conducted by recruiting consecutive outpatients examined in a specialized Balance Clinic at an otolaryngology clinic at a University hospital. The patients were referred from primary or specialist care due to dizziness or balance problems.Patients aged 18–67, were eligible for inclusion if dizziness had lasted at least three months. Inclusion period was between August 2020 and January 2022 and a total of 164 patients were invited to participate in the study. Hospitalized patients and patients with neurological disorders  or other serious comorbidities  that potentially could affect physical functioning were excluded. Patients with vestibular schwannomas, divers investigated for neuro-otologic disorders, and patients from other health authority regions were also excluded. The patients had to have sufficient knowledge of Norwegian to fill in the questionnaires. Of the 164 eligible patients, four declined to participate, ten were later excluded, leaving 150 included patients  including Benign Paroxysmal Positional Vertigo (BPPV), vestibular migraine, Ménière disease, and unspecified episodic syndromes; Chronic vestibular syndrome (AB32 codes) including Persistent Postural-Perceptual Dizziness (PPPD), vestibulopathy and specified or unspecified chronic syndromes, and other  including panic attack and abnormalities of gait and mobility , according to the International Classification of Diseases ICD-11). Discrepancy between the specialist were further resolved by consensus. If the patient had several diagnoses, the one determined as the main diagnosis was included in the analysis. The diagnoses were further categorized into three categories corresponding to the ICD-11 coding system: 1. DiscreThe Dizziness Handicap Inventory (DHI)  quantifiThe Vertigo Symptom Scale – Short Form (VSS-SF) has satisfactory internal consistency and test–retest reliability and measures the frequency and severity of dizziness symptoms . VSS-SF The Standardized Nordic Pain Questionnaire (SNQ) traces the localization of musculoskeletal pain or discomfort by the following question: “Do musculoskeletal troubles occur in a given population, and if so, in what part of the body are they localized?” , 26. ThePain intensity during the last seven days was reported by an 11-point (0–10) Numeric Rating Scale (NRS) where 0 equals “no pain at all” and 10 equals “worst imaginable pain”. NRS is reported to be valid and reliable , 28. NRSDizziness Catastrophizing Scale (DCS) measures dizziness-related catastrophizing. It comprises 13 self-reported items, scored on a 5-point (0–4) Likert-type of scale where 0 equals “not at all” and 4 equals “all the time” . The totDescriptive statistics were used for demographic data, test scores, prevalence of pain, and pain pattern distribution; and are presented as mean, median, and frequency distribution as appropriate. Continuous variables were assessed and deemed normally distributed using visual inspections of histograms and qq-plots.Linear regression analysis was used to estimate the association between pain (NPS and NRS) as dependent variables and dizziness  as independent variables, and was examined in crude and adjusted models. Confounding variables (age and sex) were included in the adjusted regression models. The alpha level was set to 0.05. Of the 150 included participants, four had missing data, which was deemed insignificant to the results. The statistical software package Stata 17 was used for the data analysis.www.wma.net) and the personal data were administered following the standards of the General Data Protection Regulation (GDPR). To provide transparency, the study was registered in the Clinical Trials database (NCT04241822 27/01/2020) prior to the data collection. The authors declare no conflict of interest.The study was approved by the Regional Ethical Committee (REK) (REK 2019/6849) and Norwegian Centre for Research Data (NSD), and committed to the criteria laid in the current (2013) Declaration of Helsinki  years. Median duration of dizziness was 21.5 (range 3—509) months. Sick leave or disability was reported by 43%, of those, 60% stated dizziness as the cause. Episodic vestibular syndromes were diagnosed in 65% of the patients, while 33% were diagnosed with a chronic vestibular syndrome. Four patients received a non-vestibular diagnosis. Average number of pain sites was 4.5. Higher intensity of pain and higher number of pain sites were seen among patients on disability benefits and among those patients who reported severe dizziness (VSS-SF ≥ 12) and moderate to severe dizziness-related handicap (DHI ≥ 30). Females tended to have a higher number of pain sites and higher pain intensity than men. The clinical and demographic characteristics are listed in Table The majority 94.5%) of the patients reported pain or discomfort in at least one body site during the past week. Figure .5% of thLinear regression analysis showed a statistically significant positive association between the number of pain sites (NPS) dizziness severity (VSS-SF) and dizziness-related handicap (DHI) Table . There wThis study found that most of the patients with dizziness reported pain (94.5%), with an average of 4.5 number of pain sites. Number of pain sites and pain intensity were associated with the dizziness severity. Number of pain sites was also associated with dizziness-related handicap.The high prevalence of pain reported in our study is in line with other studies on patients with dizziness , 17, 18.The high prevalence of pain in our patients may therefore indicate a greater health burden and risk of future health problems. There seemed to be no difference in pain across the three diagnostic categories. Pain, including the number of pain sites, should therefore be taken into consideration in the examination and treatment of all patients with persistent dizziness.The pattern of pain localization, where the neck, back, and shoulders are the most reported pain sites, is similar to what reported in other studies on patients with dizziness , 34 and p = 0.00) as well as dizziness-related handicap (DHI) (p = 0.03). The number of pain sites may therefore be an indicator of a greater symptom-burden of dizziness and could perhaps influence dizziness symptoms. This is consistent with a previous study from Malmström, Magnusson [The regression analysis showed a statistically significant association between number of pain sites and dizziness severity (VSS-SF)  as the confidence intervals contains the value of zero, although there was a tendency for higher pain intensity and NPS in the group with DHI scores ≥ 30 Table . This isThe population in this study was patients referred to a specialized otolaryngology clinic due to dizziness. The study population may differ from other persons with persistent dizziness treated in primary care, as they are referred to a specialized clinic due to the severity of complaints, introducing a selection bias. Selection bias may also exist due to the Covid-19 pandemic, as some patients may for this reason have canceled their appointments at the hospital. However, as only four out of 164 patients refused to participate in the study, it is reasonable to assume that the results are representative of the patients referred to the balance clinic in this period.It is challenging to assess patients with complex conditions and the included outcomes could have shortcomings in capturing central aspects of both dizziness and pain. The SNQ questionnaire does not distinguish between musculoskeletal pain and other types of pain such as neuropathic pain. Many patients are, however, unable to distinguish between the different types or etiology of their pain, therefore, we cannot exclude that some of the reported pain may be of other causes such as sciatica, carpal tunnel syndrome, or organ-related pain. When comparing our study population to the general population, the same measuring tools were used making the comparisons more reliable. A causality between musculoskeletal complaints and dizziness was not possible to establish due to the cross-sectional design.Future research should examine possible predictive relationships between dizziness and musculoskeletal symptoms. Another important aspect would be to address the patients’ perceptions of how pain and dizziness influence each other, and how both interfere with daily life, through a qualitative study. Both types of studies would provide insights that potentially could lead us towards more tailored rehabilitation for these patients.The prognosis of persistent dizziness is poor in many cases , 37, henThe prevalence of pain and number of pain sites are considerably higher in our study sample of patients compared to the general population. Both number of pain sites and pain intensity were associated with dizziness severity. The localization of pain sites and the pain intensity are however in line with what is seen in the general population in Norway. The diagnostic category does not seem to play a role when dizziness persists, as the number of pain sites and pain intensity were similar between groups.These findings may indicate a greater health burden and an increased risk of future health problems in patients with persistent dizziness. Musculoskeletal pain, including the number of pain sites, should therefore be taken into consideration in the examination and treatment of these patients.Additional file 1. The distribution of diagnoses in the study sample, according to the ICD-11 system.


Local anaesthetic infiltration is widely used to reduce pain after laparoscopic cholecystectomy (LC). This trial evaluated the effect of depth of local anaesthetic infiltration on postoperative pain reduction after LC.Patients undergoing elective LC between March 2018 and February 2019 were randomized into no infiltration, subcutaneous infiltration, and rectus sheath infiltration using bupivacaine. The primary outcome was 24-h postoperative cumulative morphine use, and the secondary outcomes were mean 24-h Numerical Rating Scale (NRS) for pain, and nausea, and vomiting. Subgroups were compared and multivariable analyses were performed.P = 0.001). The 24-h cumulative morphine use in the rectus sheath infiltration group was significantly lower than in the no-infiltration group (P = 0.043), but no difference was observed between the subcutaneous infiltration and no-infiltration groups (P = 0.999). One hour after surgery, the rectus sheath infiltration group had a significantly lower NRS score than the no-infiltration and subcutaneous infiltration groups respectively (P = 0.006 and P = 0.031); however, the score did not differ among the three groups at any of the time points from 2 h after the surgery. The incidence of nausea or vomiting was comparable among the three groups. Multivariable analysis documented that a lower dose of morphine use was associated with rectus sheath infiltration (P = 0.004) and diabetes (P = 0.001); whereas, increased morphine use was associate with age (P = 0.040) and a longer duration of surgery (P = 0.007).Out of 170 eligible patients, 162 were selected and 150 patients were analysed: 48 in the no-infiltration group, 50 in the subcutaneous infiltration group, and 52 in the rectus sheath infiltration group. The groups had similar clinical features, although mean BMI was higher in the subcutaneous infiltration group .TCTR20201103002 ( Local anaesthetic infiltration into the rectus sheath reduced postoperative cumulative morphine use in patients undergoing laparoscopic cholecystectomy; however, infiltration into the subcutaneous tissue alone did not affect postoperative pain control. Many methods have been developed for postoperative pain control, including local anaesthetic infiltration, which is widely used and may hasten patient recovery; however, its effectiveness remains controversial. A meta-analysis published in 2014 showed that local anaesthetic wound infiltration reduces postoperative pain in the first 24 h, without increasing the incidence of serious adverse events, but the quality of the studies on which it was based was low and a great variety of anaesthetic infiltration methods were used4. Therefore, this randomized clinical trial (RCT) aimed to compare the effect of different depths of local anaesthetic infiltration on postoperative pain control in patients undergoing LC.Cholecystectomy is one of the most performed procedures globally. Laparoscopic cholecystectomy (LC) is now the standard because it is associated with less postoperative pain, faster recovery, and a shorter duration of hospital stay than an open approachThis RCT was conducted at Ramathibodi Hospital, Mahidol University, between March 2018 and February 2019. The study was approved by the Committee of Research, Faculty of Medicine, Ramathibodi Hospital, Mahidol University (EC no. 10-61-04). Ramathibodi Hospital is a teaching hospital performing 200–250 cases of elective cholecystectomy per year.The study recruited patients who were scheduled for elective LC, aged 18–85 years, and ASA class I–IV. Patients who were diagnosed with liver cirrhosis, concurrent common bile duct cholelithiasis, acute pancreatitis, or critical illness; had a history of bupivacaine or morphine allergy; or needed surgical drain placement or conversion to open cholecystectomy were excluded from the study. The participants were informed about the procedure by a researcher and gave written consent on the admission date, before surgery. All patients were routinely admitted to the hospital 1 day before and discharged the day after the operation and were followed up at the outpatient clinic 1 week and 2 months after surgery.Preoperative anaesthetic evaluation was performed and an intravenous (i.v.) patient-controlled analgesia (PCA) method was recommended by anaesthetists before surgery.Participants were randomly allocated to three groups by way of computer-generated block randomization. Group 1 consisted of participants who did not receive local anaesthetic infiltration (no-infiltration group); group 2 consisted of participants who received local anaesthetic infiltration into the subcutaneous layer (subcutaneous infiltration group); and group 3 consisted of participants who received local anaesthetic infiltration into the rectus sheath and subcutaneous layer (rectus sheath infiltration group). In the subcutaneous infiltration group, 10 ml 0.5 per cent bupivacaine was injected at multiple sites into the subcutaneous layer of each surgical wound, and in the rectus sheath infiltration group, 5 ml 0.5 per cent bupivacaine was injected into the abdominal sheath of the infra-umbilical wound (∼10 mm in length) and 5 ml was injected to the subcutaneous layer of each wound, including the infra-umbilical wound.Randomization numbers were written on pieces of paper and placed in opaque, sealed envelopes, which were opened in the operating room by nurses after each patient’s gall bladder and all the instruments were removed. The participants were blinded to their group allocation and the individuals who opened the envelopes did not participate in the postoperative pain control or observation. The surgeons were not blinded to the participants’ group allocations, but they did not participate in postoperative pain control or its assessment.Fig. 1).LC was performed by staff surgeons and residents, under close supervision. A total of three to five ports were used in each patient: a 10-mm trocar was inserted through the infra-umbilical incision by way of an open approach, then two to four more 5-mm trocars were inserted through incisions in the epigastric and right costal margin areas after creating a pneumoperitoneum. The intra-abdominal pressure was maintained between 12 and 15 mmHg during the procedure. Local anaesthetic infiltration was performed according to the group allocation at the end of surgery. For the rectus sheath infiltration group, the rectus sheath of the infra-umbilical incision was clearly identified by hanging sutures, which were placed at the time of trocar insertion. Then, 5 ml 0.5 per cent bupivacaine was directly infiltrated, resulting in swelling of the rectus sheath and the underneath peritoneum  with morphine was commenced when the participant’s pain score was lower than 3. Postoperative PCA morphine administration consisted of a 1-mg bolus, a lockout interval of 5 min, and a 4-h limit of 40 mg. The number of times that the patients pressed the i.v. PCA button and when were recorded automatically by the device and this was reviewed by researchers.General anaesthesia was induced in all the participants. Fentanyl at 1.5 µg/kg was administered at the induction of anaesthesia and a minimal alveolar concentration of sevoflurane of 1–1.5 per cent was used to maintain anaesthesia; no further analgesia was provided. In the postoperative care unit (PACU), the pain score of the participants was evaluated with the Numerical Rating Scale (NRS) by the attending anaesthetists. Three milligrams of i.v. morphine were administered if the pain score of the participants was more than 3, and it was reassessed 15 min later. The i.v. PCA , based on the s.d. obtained from the same study, was assumed to be 11 mg2. STATA version 14  was used to calculate the sample size, with the ‘power oneway’ command, obtaining 49 patients per group, a 10 per cent expected dropout in each group was added; on this basis, the final number of participants allocated per group was 54.The sample size was calculated to detect any significant difference in total morphine consumption among the three randomized groups at the 5 per cent level, with a power of 80 per cent. The mean total morphine consumption for the sample size calculation was obtained from a previous, similar research(s.d.) and categorical data are expressed as frequencies and percentages. Categorical data were analysed with a chi-squared test and continuous data were assessed with a one-way ANOVA or Kruskal–Wallis test. The factors associated with the level of morphine use were identified with a non-linear regression model that was based on an empirical mathematical relationship between morphine use and time. Estimates of these parameters and the associated 95 per cent confidence intervals (c.i.) were obtained with non-linear least squares, with estimated s.e. adjusted for clustering around individuals. P < 0.05 was considered to represent statistical significance and only significant predictors were included in the final model. The final equation of the multivariable analysis of the predictors associated with the total amount of morphine used was PCAtotal(t) = 6.651 + a1[(anaesthetic group)(optime)(diabetes millitus)] x (1-expt +(–0.003)age(−0.375)).Statistical analysis was performed with STATA version 14 . Continuous data are expressed as meanFig. 2). The characteristics of the participants, operating factors, and operating outcomes are summarized in Tables 1 and 2. The characteristics and operating factors of the three groups were similar: there were no differences in sex distribution, age, ASA physical status, distribution of diagnoses, number of surgical incisions, pneumoperitoneum pressure, duration of surgery, or estimated blood loss; however, mean BMI was higher in the subcutaneous infiltration group (P = 0.001). There were also no differences in the incidence of perioperative complications. The number of participants who required analgesia in the PACU was highest in the no-infiltration group and lowest in the subcutaneous infiltration group, but the differences between the groups were not statistically significant (P = 0.198). The duration of hospital stay was not different among the three groups due to the routine admission protocol of our hospital; consequently, this variable was not analysed as the outcome.A total of 170 patients underwent LC during the study interval, of whom 4 patients who required conversion to open cholecystectomy and 4 patients who required surgical drain insertion were excluded, such that 162 participants were randomized to the three groups. Overall, 12 participants dropped out of the study due to incomplete data on postoperative morphine use. The total number of participants analysed in the study was 150 (P = 0.043) and tended to be lower than that by participants in the subcutaneous infiltration group ; however, no significant difference was found in the 24-h postoperative morphine use by the no-infiltration and the subcutaneous infiltration groups (P = 0.999) .The amount of morphine administered after surgery was highest in the no-infiltration group and lowest in the rectus sheath infiltration group at every time point. The mean 24-h cumulative morphine use by participants in the rectus sheath infiltration group was 3.36 mg lower than that by participants in the no-infiltration group (P = 0.014) immediately following surgery. One hour after surgery, the rectus sheath infiltration group had significantly lower NRS scores than the no-infiltration group (P = 0.006) and the subcutaneous infiltration group (P = 0.031); however, no difference in NRS scores was observed between the no-infiltration group and the subcutaneous infiltration group at either time point. The NRS score did not differ among the three groups at any of the time points from 2 h after surgery .The pain intensity was highest immediately after surgery, then gradually decreased. The rectus sheath infiltration group had significantly lower NRS score than the no-infiltration group (Table 2)Most of the participants did not have nausea and vomiting after the operation and no differences in the incidence of postoperative nausea and vomiting was observed among the three groups.  in all the participants from 3 h after surgery; however, the duration of the pain reduction induced by local anaesthesia differed among the many previous studies. Some studies demonstrated an analgesic effect only during the early postoperative interval (0–6 h)8–10, whereas others showed a longer-lasting effect (12–24 h)12. Various techniques, sites of infiltration, doses of anaesthetic, and postoperative analgesia regimens were used in these studies, which would have affected the duration of its effect.In the present study, a significant difference in pain score was found immediately and 1 h after surgery, which is not consistent with the findings of the first trial, perhaps because of the different methods of postoperative pain control used. An intramuscular injection of pethidine and oral naproxen was used for postoperative pain control in the previous study, whereas we used i.v. PCA with morphine, which is a widely used, and effective method of postoperative pain control12, whereas the study in which bupivacaine was infiltrated around trocar sites into the subcutaneous tissue alone showed no significant effect on postoperative pain reduction versus placebo13. These findings are consistent with the present finding that subcutaneous infiltration did not significantly affect postoperative pain control, whereas infiltration into the rectus sheath had a beneficial effect.Previous studies have also yielded inconsistent findings regarding the effects of anaesthetic infiltration around LC incisions, but various depths of portal wound infiltration were used in these studies. The studies in which anaesthetic was infiltrated into all the layers of the abdominal wall, including the subcutaneous tissue, fascia, and parietal peritoneum, showed significant reductions in postoperative painIn the present study, bupivacaine was infiltrated into the rectus sheath and into the subcutaneous layer at the sub-umbilical incision, whereas at the other three incisions, bupivacaine was infiltrated into the subcutaneous tissue alone. This approach was chosen because the sub-umbilical incision is large and likely causes more pain than the other incisions; we routinely used an open technique for the sub-umbilical trocar insertion, where the layers of the abdominal wall can be clearly identified, such that accurate anaesthetic infiltration can be easily performed; and this technique is simple, requiring no additional resources, and could therefore be easily used in clinical practice.14 but several studies demonstrated a contradictory result15. Therefore, the best timing of infiltration is still debatable; however, an advantage of postoperative infiltration would be the precision of the injection of anaesthesia into the particular layers of the abdominal wall, especially at the umbilical wound, because the skin is already open.The timing of anaesthetic infiltration has been investigated in previous studies; however, the result are inconsistent. Several studies demonstrated that preoperative incisional infiltration had better effect on postoperative pain control than postoperative infiltration17. Several RCTs have been conducted to compare the effects of TAP block with local anaesthetic infiltration; however, they showed contradictory results18–20. The previous RCT evaluated additional effects of TAP block in participants who received standard port site infiltration; the study concluded that TAP block did not give additional pain relief or other favourable outcomes21. Heterogeneous techniques of the TAP block and local anaesthetic infiltration were observed among the published studies. To compare the TAP block with local anaesthetic infiltration, more studies and standardized techniques are required. Continuous wound infusion was another method that had effects on postoperative pain reduction in various types of surgery22. The previous RCT compared perioperative continuous ropivacaine wound infusion with normal saline wound infusion and showed that the ropivacaine group had better pain control than the normal saline group up to 4 h after surgery23; however, there have been no studies comparing continuous wound infiltration with local anaesthetic infiltration to date.Other methods of postoperative pain control have been proposed. Transversus abdominis plane (TAP) block showed beneficial effects on postoperative pain control in LC compared with placebo24. Low-pressure cholecystectomy was safely performed by an experienced surgeon25. In our centre, low-pressure cholecystectomy was selectively performed but the data were not included in the present study. A combination of low-pressure pneumoperitoneum and local anaesthetic infiltration may provide a greater effect on postoperative pain reduction and may be an area for future studies.The meta-analysis demonstrated that a low-pressure pneumoperitoneum was safe and resulted in reduced postoperative pain, rate of analgesic used, and duration of hospital stay26. A systematic review published in 2009 showed that age negatively correlates with postoperative analgesic use and pain intensity. Many factors may contribute to this finding, including blunted peripheral nociceptive function, postoperative confusion and under-reporting of pain, high sensitivity to analgesics, and pharmacokinetic change, such as changes in drug metabolism or elimination27.According to the present findings, older patients require a lower dose of morphine for postoperative pain control than younger patients, which is consistent with the results of another recent study of LC, showing that the postoperative pain rating decreased with increasing age28; therefore, prolonged carbon dioxide insufflation may cause more postoperative pain and result in the use of more analgesics. The experience of surgeons influences the duration of surgery, which might also affect postoperative pain and the analgesic used; however, no study has addressed this issue to date and future studies are required.A prolonged duration of surgery was associated with a higher total dose of morphine. A long duration is a common feature of complex surgery and challenging cases, and is associated with more manipulation in the surgical field and greater tissue trauma around the trocar sites. Additionally, carbon dioxide, which is used for creating the pneumoperitoneum, promotes postoperative pain as a consequence of the build-up and accumulation of carbonic and lactic acid at the peritoneal membrane29.Diabetes mellitus (DM) was associated with a lower requirement for postoperative morphine in the present study: participants with diabetes used 3.54 mg less morphine in total than those without. A previous study of patients undergoing cardiac surgery showed that those with DM had lower postoperative pain scores than those without, which the authors ascribed to poorer sensation, secondary to peripheral neuropathy31. To accurately investigate effects of local anaesthetic infiltration on postoperative morphine use without being obscured by the effects of other types of analgesia, other analgesic drugs were omitted, including NSAIDs. Fourth, the patients were routinely admitted 1 day before and discharged 1 day after the operation, so the duration of hospital stay, which is a key outcome, could not be evaluated in the present study. Last, we used a total of 10 ml 0.5 per cent bupivacaine to infiltrate the surgical wounds or rectus sheath, but in a future study, the effects of a larger amount of local anaesthetic should also be investigated.The present study had several limitations. First, visceral pain was not controlled with a specific procedure, and therefore this type of pain may have contributed to the overall postoperative pain score and requirement for morphine. Second, analgesia was provided in the form of a combination of intraoperative fentanyl and postoperative PCA morphine, and therefore did not include multimodal analgesia, such as i.v. dexamethasone, paracetamol, non-steroid anti-inflammatory drugs (NSAIDs), or nefopam. The assumption made was that the pain score and morphine consumption would be lower if these analgesics had also been used. In the pilot study, most of the patients had low postoperative pain scores, even in some patients who did not receive perioperative NSAIDs. Additionally, several previous studies showed that perioperative NSAIDs provided no significant effect on postoperative pain relief and opioid consumption after LCBased on these findings, deep local anaesthetic infiltration into the rectus sheath lowers immediate (within 2 h) postoperative pain scores and use of morphine during the first postoperative day after LC but subcutaneous infiltration alone has no effect on pain control.zrac066_Supplementary_dataClick here for additional data file.


Pain intensity during the 72 h postoperatively and the incidence of chronic pain 3 months after surgery did not differ between the groups. Intraoperative nefopam did not decrease acute postoperative opioid consumption or pain intensity, nor did it reduce the incidence of chronic pain after VATS.Nefopam is a centrally acting non-opioid analgesic, and its efficacy in multimodal analgesia has been reported. This study aimed to assess the analgesic efficacy of intraoperative nefopam on postoperative pain after video-assisted thoracoscopic surgery (VATS) for lung cancer. Participants were randomly assigned to either the nefopam or the control group. The nefopam group received 20 mg of nefopam after induction and 15 min before the end of surgery. The control group received saline. The primary outcome was cumulative opioid consumption during the 6 h postoperatively. Pain intensities, the time to first request for rescue analgesia, adverse events during the 72 h postoperatively, and the incidence of chronic pain 3 months after surgery were evaluated. Ninety-nine patients were included in the analysis. Total opioid consumption during the 6 h postoperatively was comparable between the groups (nefopam group [ Severe postoperative pain after thoracic surgery interferes with deep breathing and coughing and reduces pulmonary function, which increases the incidence of postoperative pulmonary complications ,2. FurthNefopam is a centrally acting, non-opioid, non-steroidal analgesic drug, and its efficacy in multimodal analgesia has been reported in some previous studies ,12. The Although the analgesic efficacy of nefopam was reported in several surgeries, including abdominal and orthopedic surgeries ,16,17,18http://cris.nih.go.kr). Screening and enrollment for the study were conducted between March 2021 and September 2021 at a tertiary academic hospital in Seoul, South Korea. Written informed consent was obtained from all participants. This study was performed in accordance with the ethical principles of the 1964 Declaration of Helsinki and its later amendments. The trial was conducted following an original protocol and CONSORT guideline  according to their normality, which we evaluated with the Shapiro–Wilk test. The n = 50) or nefopam (n = 50) group. One patient allocated to the nefopam group dropped out because of withdrawal of consent. The operations of 4 patients were converted to thoracotomy, and 11 patients underwent a wedge resection or segmentectomy due to intraoperative changes in the surgical plan. Those 15 patients are included in the analysis based on the intention-to-treat principle. Therefore, 99 patients completed the 72 h follow-up. Of them, 75 patients  completed the 3-month follow-up measures.A flow diagram of the study is shown in p = 0.013; The baseline demographics and intraoperative data were comparable between the groups, except that the infusion dose of intraoperative remifentanil was higher in the nefopam group . Opioid consumption during the PACU stay and at 12, 24, and 72 h postoperatively was also comparable between the two groups. These data are shown in detail in p = 0.302; Total opioid consumption during the first 6 h postoperatively did not differ between the nefopam and control groups . Among the 45 patients who answered that they had persistent pain, the pain scores differed insignificantly between the groups . The severity of pain and numbness was also comparable between the groups  indicated that they had at least one neuropathic pain component, and the incidence of neuropathic pain did not differ significantly between the groups  3 months after surgery were all in the control group. Although there was no statistically significant difference between the groups, that result could suggest that nefopam has a potential role in attenuating severe pain in CPTPS. Further studies will be needed to clarify the effect of nefopam on chronic postoperative pain.A characteristic finding of this study is that the dose of remifentanil infused during surgery was significantly higher in the nefopam group. We attribute that finding to the tachycardia effect of nefopam . HoweverThis study has several limitations. First, the patients in this study were not completely blinded. Although they did not know which group they were in during the acute postoperative period, they could have known their group if they read their medical records later. Second, we only evaluated postoperative pain intensities at rest. Assessing pain scores during coughing or movement would have been more appropriate. Third, we could not evaluate the incidence of tachycardia and sweating during the perioperative period, and they are known to be frequent adverse effects of nefopam. However, it was difficult to evaluate the occurrence of tachycardia during surgery because many factors can induce tachycardia during VATS. Fourth, the chronic pain evaluation was conducted by telephone, rather than in face-to-face interviews. Finally, the sample size of this study was not determined by the incidence of CPTPS. Furthermore, only 37 patients in the control group and 38 patients in the nefopam group were evaluated chronic pain at postoperative 3 months due to the follow-up loss. This sample size was rather small to demonstrate the incidence of chronic pain or compare it between the two groups.In conclusion, intraoperative nefopam administration did not decrease total opioid consumption or postoperative pain intensity during the first 72 h after VATS for lung cancer. It also did not reduce the incidence of chronic post-surgical pain 3 months after surgery, compared with the control group. Further studies are required to elucidate the potential role of nefopam in multimodal analgesia for patients undergoing VATS.


Background: There are many therapeutic methods targeting fascia. However, the only method whose basic assumption is to eliminate the densification of fascia is Fascial Manipulation. Objective: To evaluate the effectiveness of various Fascial Manipulation (FM) protocols in reducing myofascial pain. Design: Randomized control trial. Subjects: A total of 54 individuals, aged 18–29 years, with musculoskeletal pain for at least 1 week. Methods: The patients were divided into four groups subjected to different treatment protocols: group 1—underwent the standard FM treatment protocol (STP), group 2—modified protocol (MTP), group 3—modified protocol 2 (MTP2), and the control group (CG)—did not undergo any therapy. Each protocol involved three treatments at intervals of 7–10 days and a follow-up examination after 30 days. The outcome was pain level measured using the VAS. Results: In the STP, all the measurements showed a significant decrease in pain level—the mean difference was 2.077 after the first treatment, 3.462 after the third treatment and 3.385 in the follow-up. In the MTP, a significant mean difference was noted after the third treatment, 3, and in the follow up, 2.4. In the MTP2, it was noted after the third session, 2, and in the follow up, 2.25. Only the CG group did not display significant changes. Conclusions: FM-based therapy results in pain relief. However, there are differences in the dynamics and durability of the results depending on the chosen protocol. Myofascial pain (MP) is a very common problem, possibly one of the most frequent causes of muscle pain reported by patients to their GPs ,2. UnforThe Global Burden of Disease estimated that low back pain is responsible for the loss of a total of 83 million years of life, which people from around the world have had to devote to adjust to their disability . In the case of neck pain and headaches (including migraines), this value is around 24 million years, and other musculoskeletal dysfunctions take 28 million years of human life around the world [Over the recent years, there have been many publications aimed at understanding the structure and function of fascia. It turns out that fascia is a very richly innervated structure ,10. Due Many therapeutic methods and systems target fascia. However, the only method whose basic assumption is to eliminate the densification of fascia  is Fascial Manipulation. According to this concept, it is a disorder of hyaluronic acid quality that leads to the dysfunction of the myofascial system, which, among others, results in the deterioration of joint movement and pain. The analyses made by Stecco et al. indicate that there is a strong correlation between myofascial pain and hyaluronan (HA)-rich matrix disorders . An acceWhat seems to be essential is to determine whether by using this method, and theoretically improving the viscoelastic properties of fascia, we are able to alleviate pain and/or improve the functional parameters of fascia.The aim of the study is to evaluate the effectiveness of various Fascial Manipulation (FM) protocols in reducing myofascial pain.(1)What is the effect of Fascial Manipulation therapy on the level of subjective pain sensation, as measured using the VAS?(2)Does the protocol of FM treatment affect the patient’s response?The research questions are:The research project was designed as a randomized, double-blind trial. The Ethics Committee of the Jerzy Kukuczka Academy of Physical Education in Katowice, Poland, approved of the study (ref. 1/2017). A written informed consent was obtained from each participant prior to data collection, and the trial was registered under the number: ISRCTN13533739.First of all, the patients were examined. The examination, carried out by diagnosticians, included history taking, pain assessment and palpatory verification based on the Fascial Manipulation method. The project coordinator then randomly assigned each patient to one of four groups  so that the diagnosticians could select the centers of coordination in accordance with the group including particular patients. The diagnosticians indicated chosen points to the therapists, and then the points were subjected to the treatment protocol. The therapists were not familiar with the treatment methodology according to the Stecco method; therefore, they did not know to which research group a patient belonged.The first therapy session took place on the day of examination. After the treatment, pain was again assessed according to the VAS scale. The next meeting was arranged after 7–10 days and was only therapeutic in character. The third session took place 7–10 days after the second one and was therapeutic as well as diagnostic. Thus, the patient was first subjected to the therapy, and next the pain was assessed according to the VAS. The last meeting, the fourth one (follow-up), was arranged 30 days after the end of the therapy, where the pain assessment was carried out according to the VAS scale for the last time. As for the individuals from the control group, during the first appointment they had a 45 min break between subsequent pain tests, they did not come to the second meeting, and during the third and fourth one (follow-up), they marked their pain levels on the VAS scale. The patients were asked to sit still for 45 min. The examination schemes are presented in The study included 54 individuals aged 18–29 years, 31 women and 23 men. The inclusion criteria were age 18–30 years and the presence of musculoskeletal pain for at least 4 weeks. Choosing young and active adults as participants allowed the researchers to minimize the risk of chronic disorders and older age-related dysfunctions. The exclusion criteria included chronic or systemic concomitant diseases, pregnancy, the use of steroids, anti-inflammatory drugs or drugs that affect blood coagulation, the use of other therapeutic forms and serious neurological disorders. Patients with a previous history of trauma or surgery were allowed to participate in the study.The study was conducted by a team of researchers, including a project coordinator, 2 people conducting diagnostic procedures (who have completed the second level of FM training) and 4 people responsible for performing the therapy . Prior to the study, the individuals carrying out the treatment underwent a 6-month preparatory period, where they were trained in technically performing the procedure and improved their skills of working with densifications.The participants were assigned to particular groups by means of a draw arranged before the beginning of the experiment. The allocation to one of the four groups was determined by the sequence of entering the study. In this process, the gender of the individuals was not taken into account. As a result, the groups were unequal in size and imbalanced in terms of gender distribution.The interview, data collection and palpatory verification were performed in accordance with the Fascial Manipulation method.In all the three therapeutic groups, work with the patients involved manipulation (deep rubbing) of 6 centers of coordination, which had previously been selected by a diagnostician. Each of these sites was rubbed 3 times for 3 min , in a rotational system  . During The first group (STP) was subjected to the therapy in accordance with the standard treatment protocol of the Fascial Manipulation method. This means that the so-called palpatory verification was followed by determining the plane  with the largest extent of fascial disorder, that is, the plane with the most severe densifications within the centers of coordination. Then, 6 centers of coordination were selected in the most disturbed plane in such a way that the tension balance (based on points from two opposing movement sequences) was maintained. Therefore, when choosing the sagittal plane, the selected points had to include those from the anterior (AN) and rear (RE) sequences; when choosing the frontal plane, the lateral (LA) and medial (ME) sequences had to be addressed through the points covered; finally, when selecting the transverse plane, the sequence of external rotation (ER) and internal rotation (IR) had to be included.In the second group (MTP), the therapy was carried out according to the modified FM protocol. In this group, the second most disturbed plane was chosen and CC points from two balancing sequences were also selected.In the third group (MTP2), the modified FM 2 protocol was applied, which included centers of coordination randomly selected from all the segments subjected to the palpatory verification. In other words, the centers could belong to different zones and could not be balanced in any way.The only side effects of the procedure were bruising and mild pain in the area of manual manipulation. These effects subsided 1–3 days after the intervention.The last group included controls, who did not undergo any treatment.The primary outcome measure was a subjectively evaluated level of pain. The tool used for this purpose was the VAS. In the course of the examination, each patient received a 10-centimetre-long line segment marked with 0 (meaning no pain), 10 (maximum level of pain) and 5 in the middle. The patients’ task was to mark the place in the segment that corresponded to the subjectively felt level of pain.The VAS measurement was performed 4 times: before the first therapy session, directly after the first session, after the third treatment and during the follow-up.p < 0.05 was assumed as the statistical significance level. Next, the differences between the mean VAS scores at particular assessment times within the groups were calculated. The confidence intervals were computed at the 95% level.All the collected data were transferred to SPSS program and analyzed using the two-way repeated measures ANOVA, Box’s Test of Equality of Covariance Matrices, Multivariate Tests (Wilks’ lambda), Tests of Within-Subjects Effects (Greenhouse–Geisser), Levene’s Test of Equality of Error Variances, Tests of Between-Subjects Effects and Tukey’s test HSD. The value of The basic anthropometric data of the examined patients from particular groups are presented in The flow of the participants is presented in The mean VAS levels in particular groups at subsequent measurements are presented in p > 0.05). Wilks’ lambda test showed that the variation in the means on pain level (VAS) over the repeated measurement occasions itself varies as a function of treatment group membership . Similar outcomes were also confirmed with the greenhouse–Geisser test.Box’s test indicated that the covariance matrices were homogenic  across the treatment groups with respect to the average VAS level .The tests of between-subjects effects indicated that there are significant differences (p = 0.005); the details are presented in Comparisons of the average VAS levels  based on Tukey’s test HSD pointed out the significant difference between the STP and CG , third  and in the follow up . In that group, the difference between the second and the third measurement was also significantly relevant . In the MTP group, a significant difference was found between the 1–3  and 1–4 measurement . In the MTP2 group, the relevant differences appeared between the measurements 1–3  and 1–4 . The details are presented in The greatest differences in the level of pain were observed in the STP group, where statistically significant changes appeared after the first therapeutic session , and select there the most severely densified centers of coordination, in a way that enables to maintain the tension balance between the two treated sequences. It should be mentioned that, in the second group of the study (MTP), the selection of points actually occurred in accordance with the selection of the most densified CC points and the preservation of the tension balance between them, accompanied by the selection of the second most disturbed plane. Therefore, the source of improvement of the patient’s condition may be due to the improvement of tension in the myofascial system resulting from the treatment of the CC points. A situation occurred in the context of the MTP and MTP2 groups, where not only was a statistically significant improvement obtained between the examination before the therapy and after the third treatment, but the effect was also maintained in the follow-up examination. It was quite surprising for the authors; however, it may be assumed that dealing with fascia, no matter on which meridians, leads to a decrease in its tension and to reduced pain level in consequence. What is worth to emphasize is that the fastest (just after the first treatment) and the greatest effect was observed with using the original treatment protocol proposed by Stecco regarding the FM concept. It can be presumed that, due to the fact that fascia is a continuous structure, the effect will appear regardless the spot of influence, but the speed and size of positive changes could be greater, if the most disturbed areas were treated in the first place. Of course, the randomness of selection of the centers of coordination for the therapy does not exclude the possibility of targeting densified points that belong to the most disturbed plane, while maintaining the tension balance, but such a situation is unlikely to happen. It should also be emphasized that, in order to maintain the therapy repeatability and to increase the reliability of examinations, the authors decided to cover the same points in three subsequent appointments. If this project is continued in the future, this fact should be taken into consideration, as constant rotation of the centers of coordination is likely to change therapeutic effects.Dibai-Filho et al.  conducteDe Meulemeester et al.  comparedRolfing is a method that assumes a holistic view of a human being. This assumption is very similar to that presented in FM. James et al.  used thiThe present study has some limitations. The main issues are unequal groups and relatively small size of samples. The reason is that the project was disturbed and interrupted by the COVID-19 pandemic. Unfortunately, after the pandemic, some people involved in the study (therapists and a diagnostician) could not continue the research. However, the results obtained to date were so promising that we considered that it would be valuable to present them as a preliminary report.The Fascial Manipulation method leads to myofascial pain reduction. Compared to the therapeutic effects achieved in the modified treatment protocol groups and in the control group, conducting the therapy in accordance with the standard treatment protocol of the FM method is the most effective way. Nevertheless, in view of obtaining statistically significant changes in the modified treatment protocols groups, further research is required to determine which mechanisms lie behind the therapeutic effects in these groups. In addition, compared to the studies cited in the discussion, therapy using the Fascial Manipulation method may guarantee effects that are faster, more significant for the patient and less costly.


Background: Joint replacement surgeries have been known to be some of the most painful surgical procedures. Therefore, the options for postoperative pain management are of great importance for patients undergoing total knee arthroplasty (TKA). Despite successful surgery, up to 30% of the patients are not satisfied after the operation. The aim of this study is to assess pain development within the first 4 weeks after TKA in order to gain a better understanding and detect possible influencing factors. Methods: A total of 103 patients were included in this prospective cohort study. Postoperative pain was indicated using a numeric rating scale (NRS). Furthermore, demographic data and perioperative parameters were correlated with the reported postoperative pain. Results: The evaluation of postoperative pain scores showed a constant decrease in the first postoperative week (mean NRS score of 5.8 on day 1 to a mean NRS score of 4.6 on day 8). On day 9, the pain increased again. Thereafter, a continuous decrease in pain intensity from day 10 on was noted (continuous to a mean NRS score of 3.0 on day 29). A significant association was found between postoperative pain intensity and gender, body mass index (BMI), and preoperative leg axis. Conclusions: The increasing pain score after the first postoperative week is most likely due to more intensive mobilization and physiotherapy in the rehabilitation department. Patients that were female, had a low BMI, and a preoperative valgus leg axis showed a significantly higher postoperative pain scores. Pain management should consider these results in the future to improve patient satisfaction in the postoperative course after TKA. Knee osteoarthritis causes pain and limited mobility. Hence, it is the main indication for total knee arthroplasty (TKA). TKA relieves pain, improves mobility, and thus increases quality of life. In Germany, primary TKA is one of the most frequently performed surgical procedures . The totProlonged postoperative pain leads to increased consumption of analgesics and a longer rehabilitation stay. Therefore, the aim of this study is to evaluate postoperative pain development and detect possible factors influencing postoperative pain after TKA.This work is a prospective study of a single center of orthopedic surgery at a university hospital, including patients undergoing primary TKA between October 2020 and July 2021. The patients were enrolled on the day of preoperative preparation, which in our department usually takes place a few days before the surgical performance.® knee prostheses . Patellar resection arthroplasty with circumpatellar electrocautery and osteophyte removal was performed on all of the patients. Patellar resurfacing was not performed. Patients who received primary TKA, anesthesia via peripheral nerve block, sedation with propofol, and inpatient rehabilitation in our department were included in the study. The follow-up for patients became easier as the rehabilitation treatment was standardized. Patients with chronic pain syndromes preoperatively and/or an intraoperative change to general anesthesia were excluded. Patients received cemented PFC Sigma  or cemented nickel-free NexGenA standardized pain management regimen was given to all patients: Preoperatively, patients were given 7.5 mg of midazolam orally one hour before surgery. The psoas compartment block was performed with 20 mL of ropivacaine 0.75% and the ischiatic nerve proximal dorsal block  with 20 mL of prilocaine 1%. The peripheral nerve block was placed using neurostimulation, and the feedback was expected to be a twitch of the leg. During surgery, patients were sedated with propofol. In the intermediate care unit, 10 mL of ropivacaine 0.75% were administered to the patients via the psoas block at regular intervals during the first 12 h after surgery. Furthermore, patients use the pain catheter at 45 min intervals with 10 mL of ropivacaine 0.75% if needed. In cases of severe pain, the ischiatic nerve block was maintained with ropivacaine 0.2 6 mL/hr.The standard oral analgesic medication, which was also given during the analgesic therapy via catheter, was metamizole 500 mg four times daily and ibuprofen 600 mg three times daily. In case of pain exacerbation, tramadol 100 mg (40 gtt) was provided, which could be repeated after 30 min when the NRS was 3–6. Also, oxycodone 20 mg could be given and repeated after 1 h in the case of an NRS of 7–10. If the patient used all therapy options, the standard analgesic medication was adjusted. Cold packs were also provided for the knee. Full weight bearing with crutches was allowed directly after surgery. The preoperative clinical status and the results one week and four weeks postoperatively were evaluated according to the Knee Society Score and Function Score (KSS and FS) .A whole-leg radiograph was performed preoperatively and a few days after surgery. The measured radiographic parameters included the anatomical axis of the leg. It connects the anatomical femoral axis with the anatomical tibial axis and forms a physiological angle of 5° to 10° valgus. A positive degree value corresponds to a valgus position, a negative one to a varus position.All patients documented their postoperative pain four times a day  and the maximum pain of the day using the numerous rating scale . In our department, the patients received physiotherapy once a day, including continuous passive motion (CPM) therapy. They got an intense rehabilitation program during the following stationary rehabilitation. The study was approved by the local ethics committee (16-101-0204). Information was supplied to all potential patients, and participation was voluntary. A written informed consent was received from every subject.p-value < 0.05 was considered as statistically significant. IBM SPSS Statistics 25  was used for analysis. Demographics and clinical characteristics were presented as means and standard deviations. Predictors of postoperative pain were analyzed using linear regression models. Leg axis and function scores were evaluated using paired t-tests. A Initially, 139 patients were included in the study. 15% of the initial data could not be used because of incomplete/missing pain sheets (n = 7), discontinuation of rehabilitation treatment due to SARS-CoV-2 infection/contact (n = 8), or a second surgical procedure on account of a complication (n = 3). The complications that led to a revision surgery included wound healing disorder (n = 1), early infection (n = 1), and arthrofibrosis (n = 1). Finally, a participation rate of 85% (n = 103) was achieved.The mean age of patients was 66.5 ± 8.7 years. Most of the patients were female . According to the classification of the World Health Organization (WHO), 8.7% of the patients were of normal weight, 34% were pre-obese, and 57.3% were obese. Indications for performing TKA were osteoarthritis (88.3%) and post-traumatic osteoarthritis (11.7%). In general, 29.1% underwent a knee arthroscopy preoperatively and 32% had already a total hip or contralateral knee arthroplasty before. One third of the patients (35%) took painkillers daily, 35.9% casually, and 29.1% of the patients did not take any painkillers preoperatively. Most patients (68%) had an ASA score (American Society of Anesthesiologists) of 2, 22.4% had an ASA score of 3, and 9.7% had an ASA score of 1.The mean duration of surgery was 82.7 ± 18.6 min . 84.5% received a cemented PFC Sigma total knee arthroplasty, and 15.5% received a cemented nickel-free NexGen implant. 61.2% of the operations were computer-assisted, and 38.8% were conventional TKAs. The pain catheter was removed at day 2.7 + 0.71  on average. p = 0.001).The mean anatomical axis of the leg showed a significant difference from 4.3 ± 7.2°  preoperatively to 7.2 ± 3.4°  postoperatively (p = 0.001) and 41 ± 17 (p = 0.001), and after 4 weeks 69 ± 17 (p = 0.001) and 55 ± 11 (p = 0.735). Accordingly, the improvement was significant even without the last FS.The clinical outcome showed a preoperative KSS of 46 ± 15 points and FS of 56 ± 16 points, 1 week postoperatively 61 ± 16  is alarming. High postoperative pain scores are associated with a higher likelihood of developing CSPS 3 months to a year after the operation . This stWhen analyzing gender as a possible predictor of postoperative pain intensity, women reported significantly higher pain scores at each surveyed level. This difference is in line with other studies ,13. Furt2). In Germany, 67.1% of men and 53.0% of women are overweight [Another known risk factor for the development of knee osteoarthritis is a high BMI ,20. Thiserweight . Therefoerweight ,23. Chenerweight . High BMerweight . It is iThe predictor age was analyzed, and no association was found in this study. Previous work, however, showed partly different results. For example, a patient aged over 70 years showed statistically significantly worse EQ-5D and WOMAC scores .In our evaluation, the type of operation was not a risk factor for more severe pain progression. Preexisting studies also found no clinically important differences between computer-assisted and conventionally performed TKR ,27,28. KSurgical time as a possible cause for increased pain intensity was also analyzed, as the duration of the operation may reflect the complexity of the implantation. The repeated resection of bone or the more frequent placement of trial implants during the procedure may influence postoperative pain development. Nevertheless, this hypothesis found no support in the present study report. The same conclusion was also reached in another prospective study .Perioperative blood loss and postoperative pain after TKA could also be issues preventing early mobilization of patients . The effIn the evaluation of the possible influence of the ASA score on the postoperative pain level, no correlation was found.The duration of the pain catheter was not found to be a possible cause of increased pain intensity. Another study  showed tThe influence of mental health on physical well-being and pain was not investigated in this study, but it also has a major role in postoperative outcome. Anxiety symptoms and depression are likely risk factors for poor outcomes . SimilarAbout 10% of all TKA patients had a valgus deformity . Valgus The main limitation of the study is the single center setting. Possible important predictors such as psychosocial factors or the radiological severity of knee osteoarthritis were not recorded. The standardized rehabilitation treatment in our rehabilitation facility could be considered a possible selection bias. Also, further information on pain progression, such as pain severity, was not collected at the 3-month follow-up visits. Another limitation is the inclusion of patients during the COVID-19 pandemic. Patients with SARS-CoV-2 infection or contact had to be excluded because they had to stop stationary therapy earlier, both in the acute hospital and in the rehabilitation clinic.In this study, the course of pain after total knee arthroplasty showed another peak after nine days. Female gender, low BMI, and preoperative valgus deformity as risk factors resulted in significantly higher postoperative pain scores. This knowledge should be taken into account by surgeons in the future to reduce patient dissatisfaction and prevent chronic pain after primary total knee arthroplasty informing the patient and by counteracting the risk factors at an early stage.Hereafter, studies should also consider psychological factors, as the perception of pain is individual.


Two of the studies (both concerning gabapentin) had no comparison arm. Conclusions: Treatments including pregabalin, methadone, ketamine, and gabapentin were found to provide pain relief against HNC NP. While there is a plethora of pharmacological treatments available for the management of NP, only a few studies have been conducted regarding the pharmacological management of therapy-related NP in HNC patients. More studies should be conducted regarding the pharmacological approaches in HNC therapy-related NP so that specific treatment algorithms can be developed.Background: Neuropathic pain (NP) in head and neck cancer (HNC) patients represents a treatment challenge. Most studies investigating drugs against NP are conducted in patients suffering with diabetic neuropathy or postherpetic neuralgia, while data are limited in cancer pain management. Additionally, regarding cancer therapy-related NP, most of the studies do not focus on HNC patients. The aim of this review is to identify the studies on systematically administered medication for NP management that included HNC patients under radiotherapy. Methods: A systematic literature search was performed, following the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines, in PubMed, Cochrane Library, Web of Science and ClinicalTrials.gov on 30 October 2021. The medical subject heading (MeSH) terms were (“head and neck cancer” OR “tumor”) AND “neuropathic pain” AND “medication” AND “radiotherapy.” The Cochrane Collaboration tool was used for quality assessment. Results: The search identified 432 articles. Three more articles were identified after searching the reference lists of the retrieved articles. A total of 10 articles met the eligibility inclusion criteria and were included in this review; 6 on gabapentin, 1 on pregabalin, 1 on nortriptyline, 1 on methadone, and 1 on ketamine. Statistically significant results in pain reduction compared to placebo or standard pain medication were found in the studies on pregabalin ( Neuropathic pain (NP) is defined as “pain caused by a lesion or disease of the somatosensory nervous system” , includiIn HNC patients, pain may be nociceptive, but more frequently, it has one or more neuropathic components ,5,6. In NP is a well-recognized problem in HNC patients ,5; treatNP represents a therapeutical challenge in cancer patients as they are already receiving several drugs . RecogniWhile there is a plethora of pharmacological treatments available for the management of neuropathic pain, only a few studies have been conducted regarding the management of NP in HNC patients under RT. The Neuropathic Pain Special Interest Group (NeuPSIG) of the IASP  , and morIn this review, we tried to identify the systematically administered drugs related to NP relief in HNC patients under RT.Full text, Clinical Trial, Meta-Analysis, Randomized Controlled Trial, Review, Systematic Review, Humans, and English and in the Web of Science, Review Articles, Early Access, Open Access, and English. In the Cochrane Library, the search was limited to title, abstract, and key words. ClinicalTrials.gov was also searched, where the “condition or disease” was “head and neck cancer,” the “other terms” was “pain medication”, and the filters applied were “with results” and “completed”. The reference lists of the articles that met the eligibility criteria were further screened to identify additional eligible studies.A systematic literature search, following the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines , was perOnly studies involving human subjects and published in English were selected. The aim of this review was to identify studies including HNC patients treated with RT and investigating the management of NP. All articles reporting NP or NP management as outcomes, as well as the ones reporting the use of adjuvant medication known for the management of NP or neuropathy were included. Articles that did not include HNC patients, did not refer to NP or medication related to NP, were not original studies, and nonpharmacological studies were excluded.After the removal of duplicates, all article titles and abstracts were screened by two authors . Any differences of opinion were resolved by a third author (AV). All articles appearing to be eligible were assessed again as full texts by two authors , and disagreements were settled by a third one (AV).The seven domains of the Cochrane Collaboration risk of bias framework  were assFollowing the identification of the eligible papers, the relevant data were extracted from each article. The included information were: study-related data ; study characteristics ; and outcome-related data .In this review, the studies are descriptively presented, based on the used drug. Due to the significant heterogeneity, it was not possible to use a meta-analytical method. Thus, it was preferred to use the “vote counting” method to draw conclusions. This method is one of the simplest ways to combine the results of many studies . Each stAs this article is based on data from previously published research and does not involve any human enrollment, ethics committee approval was not required.The research identified 432 articles. After duplicate removal, 413 of them were screened based on title and abstract, and 359 were removed because they were not consistent with the purpose of this review. Four articles were not retrieved as a full text. Forty-three articles were excluded after reading the full text; 29 of them because they did not concern HNC patients. Three articles were identified after searching the reference lists of the retrieved articles. A total of 10 articles were included in this review .Out of the 10 articles included: 3 were prospective, randomized pilot studies ,27,28; 2On the first domain “random sequence generation”, six of the ten studies had a low risk of bias ,29,30,33Pain was assessed using various scales such as VAS , the Likert scale, NRS , a 4-point scale  or opioids analgesia necessity. In the context of multidimensional, questionnaires such as OMWQ-HN , EORTC QLQ-H&N35 , VHNSSv2 (Vanderbilt Head and Neck Symptom Severity Survey version 2.0), BPI-SF (Brief Pain Inventory—Short Form), and the McGill PQ (McGill Pain Questionnaire) were used. OMWQ-HN and EORTC QLQ-H&N35 provide the responses of patients on domains related to mouth and throat soreness and pain. Neuropathic pain was assessed using DN4 (Douleur Neuropathique 4) as well as LANSSQ (the Leeds Assessment of Neuropathic Symptoms and Signs questionnaire) .The time points of pain assessment and recording varied between studies. It was either a fixed time point after the first radiotherapy session or when patients reported a specific pain score or if analgesia with used analgesics was not acceptable .The outcomes and the adverse effects of the drugs included in the review are summarized in Six out of the ten included studies explored the efficacy of gabapentin in HNC patients treated with radiotherapy ,31,32,34p = 0.002).Hermann et al.  performep = 0.004). By week 7, the median pain score in the gabapentin group was below the 0.25 quantile of the control group.Another prospective, randomized pilot trial included 79 patients . Thirty-p = 0.552). In addition, there was no statistical difference between groups either in VAS scores from baseline to 4 weeks after the treatment, at each time point between two arms or in the number of days until the use of additional analgesics.Kataoka et al. , in an op = 0.0003). Additionally, the gabapentin group had shorter overall pain duration compared to the controls . The 13% of the patients receiving gabapentin did not require additional analgesics, while, in the control group, all patients required opioids, and 70% of them required multiple opioid therapy.Starmer et al.  comparedA retrospective cohort study included 29 patients during radiotherapy treatment and receiving a median dose of gabapentin of 2700 mg per day at weeks 3, 4, 5, and 6 . Only 10In another retrospective cohort study on 42 patients, a median dose of gabapentin of 2700 mg per day at weeks 2, 3, 4, and the last week of radiotherapy was used . The patA small number of patients experienced mild side effects in all studies, ranging from 5% to 33% of the patients. The described adverse events were dizziness, nausea, vomiting, follicular skin rash/allergic skin reaction, somnolence, vertigo, headache, drowsiness, and fatigue. In one of the studies , 3% of tp = 0.003). Around 30.0% (19/64) of patients receiving pregabalin compared to 7.8% (5/64) receiving the placebo achieved pain relief of 50% (p = 0.003). At the same time, there was also a significantly greater reduction of the mean Brief Pain Inventory interference total score in the pregabalin group (13.4) compared to the placebo group (8.6) (p = 0.001). Moreover, the proportion of patients receiving pregabalin and having a reduction in pain intensity of 30% or more at week 16 was also larger compared to the placebo group (59.4% (38/64) and 32.8% (21/64), respectively, p = 0.006).A randomized, double-blind, placebo-controlled trial included 128 patients divided in two groups  . EligiblIn this study, patients experienced at least one adverse event in both the pregabalin and placebo groups . Dizziness, somnolence, facial edema, increased pain, headache, diarrhea, and peripheral edema were described as adverse events. One patient in the pregabalin group discontinued treatment because of facial edema, and two patients in the placebo group discontinued the treatment because of hospitalization for increased pain.p = 0.007 and p = 0.04, respectively). No significant changes in pain were observed within groups from baseline to 1 and 2 weeks after randomization. The Likert pain scale scores showed a nonsignificant trend toward higher pain scores in the nortriptyline group compared to the morphine group at baseline and 1 week after randomization.This study compared nortriptyline (19 patients) to oral morphine (20 patients) in a randomized trial . PatientNausea, vomiting, constipation, and CNS symptoms in 14 patients in each of the nortriptyline and control groups were reported as adverse events. In the nortriptyline group, cardiac arrhythmia was reported.p = 0.011) and 3 (p = 0.03). Improvement >50% at 1 week was higher in the methadone group compared to the fentanyl group .A randomized, controlled trial was performed on 52 patients reporting pain scores NRS > 4 and DN4 > 4 . The patXerostomia was the most common side effect in both groups , with no significant difference between the groups. Moreover, sleepiness, dizziness, nausea, vomiting, constipation, somnolence, and drowsiness were also reported. There were no serious side-effects or drop outs due to intolerable side effects.bis in die (BID) to 2.0 mg BID for technical reasons. There are also no indications on the amount of rescue medication used by the two randomized groups. Moreover, the analgesia after 5 weeks was not significantly different.This study has several limitations, e.g., the initial dosage of fentanyl was low (12.5 µg/h), and during the study, the dosage of methadone was changed from 2.5 mg Oral ketamine was evaluated as an adjuvant to oral morphine in cancer patients experiencing neuropathic pain . Out of Among the four HNC patients, three developed sedation, one vomiting, one anorexia, one nausea, three drowsiness, and one tiredness. The sedation score gradually improved despite continuing medication in all patients.This systematic review aimed to identify the successful analgesia in HNC patients under RT suffering with NP. It highlighted that despite the plethora of scientific publications on different pharmacologic therapies available for the management of NP ,21, onlyOut of the 432 articles which emerged through the database search, only 10 publications ,34,35 meGabapentin, originally an anticonvulsant, is recommended for the treatment of several neuropathic pain conditions . Pain rePregabalin is also recommended for several chronic neuropathic pain conditions . Jiang eNortriptyline, a tricyclic antidepressant, has been found to have analgesic properties and is used for management of NP, but the study included in this review did not demonstrate a better pain relief compared to opioids . NortripMethadone is a strong opioid also used for the treatment of NP as it has an action on the N-methyl D-aspartate (NMDA) receptor . HaumannKetamine, a NMDA receptor antagonist, was suggested as an adjuvant in acute pain treatment . MoreoveOur review aimed to provide a therapeutic approach for this complex pain entity. A useful algorithm for a pain clinician would be to trial a combination of an opioid with an anticonvulsant/tricyclic antidepressant agent or/and NMDA antagonist (either ketamine or action embedded within the opioid itself—methadone). A previous review by Lefebvre et al.  also appOne of the strengths of this study is that it includes the most recent publications. The database search also identified a randomized study of the team of McMenamin where the authors investigated the role of pregabalin , 300 mg This systematic review has some limitations. The literature search was not performed in all existing databases. Therefore, it is possible that some studies that support a range of potentially important pain control measures may be missed. For the 10 studies in this review, a relatively small number of patients  contributed data creating low statistical power to detect the real effects. Moreover, it was not possible to perform a meta-analysis because of the heterogeneity of the parameters reported in the studies: different pain evaluation tools, and different time points of therapies and pain assessment. A further limitation was the relatively low quality of most of the studies included, which would not make the generalizability of the findings possible.Based on the results of the examined studies, it is not possible to provide specific recommendations. Further studies, using better standardized parameters , and new potential therapies for neuropathic pain  are neceThe prompt diagnosis and treatment of NP is an important and largely unmet medical need in the HNC patient population. While there is a plethora of possible pharmacologic treatments available, only a few studies have been conducted regarding the management of therapy-related NP in HNC patients. Gabapentin, pregabalin, methadone, and ketamine were found to provide some analgesia, with good evidence only in two studies on gabapentin and one on pregabalin. Future studies looking into different pharmacological approaches in patients with HNC treated with RT with NP are necessary as patients should receive the most effective and tolerable treatment for their individual needs.


The aims of this study were to investigate the incidence of pain in peritoneal dialysis (PD) patients and to analyze the correlation between pain and quality of life.PD patients who followed up in our PD center from March 2016 to December 2017 were included. The Short-Form McGill Pain Questionnaire was used to assess pain status. Depression status, sleep quality, quality of life and clinical data were also collected.p = 0.032) and higher intact parathyroid hormone level  were independent risk factors for pain in PD patients. Multivariate analysis showed that score of pain rating index was an independent risk factor for depressive symptoms , the score of Pittsburgh sleep quality index  and the score of physical component scale  in PD patients.A total of 463 PD patients were included, of whom 153 patients (33.1%) with pain. The main cause of pain was calcium and phosphorus metabolism disorder (51.6%). About 101 patients (66.0%) had multiple sites of pain, and 28 patients (18.3%) with pain were treated with analgesic drugs. Binary Logistic regression analysis showed that older age (OR = 1.026; The incidence of pain in PD patients was 33.1%. Older age and higher intact parathyroid hormone level were independent risk factors for pain. Pain was independently associated with depressive symptoms, sleep quality and quality of life in PD patients. Pain refers to an unpleasant feeling and emotional experience that is associated with existing or potential tissue damage or is described as tissue damage , which iThis cross-sectional study investigated the PD patients who followed up in a single PD center of Southern China between March 2016 and December 2017. The inclusion criteria were age more than 18 years, receiving PD treatment more than 3 months and completing the questionnaire survey independently. Patients who had infection occurred in the last three months, acute cerebrovascular accident or paralysis, trauma, tumor, previous cervical and lumbar spine diseases or were unwilling to participate were excluded in this study. This study was approved by the Human Ethics Committee of Sun Yat-sen University and the written informed consent of patients was obtained.The Short-Form McGill Pain Questionnaire (SF-MPQ) was used to assess the pain of PD patients. This questionnaire was a multidimensional measure of perceived pain in adults. The questionnaire included pain rating index (PRI) and visual analog scale (VAS). PRI was composed of 11 sensory items and 4 affective items, which were scored from 0 (no pain) to 3 (severe pain) points. The score of PRI was calculated by the scores of 15 items, which was ranged from 0 to 45, with higher scores indicating greater levels of pain. The score of VAS was range from 0 to 100 points for average pain. The validity and reliability of this questionnaire have been demonstrated in Chinese population .The Beck Depression Inventory (BDI) was used to assess the psychological status of PD patients. There were 21 items in the scale, and each item was scored from 0 to 3 points. The total score was the sum of the score of each item. The reliability and validity of Chinese version was acceptable . This stThe Chinese version of Pittsburgh sleep quality index (PSQI) was used to assess the sleep quality of PD patients in the last month . The PSQQOL was assessed by the medical outcomes study short form-36 (SF-36) . It was At the time of PD patients being enrolled, the investigator explained the purpose and significance of the investigation to the patients, and the questionnaire was issued after obtaining the cooperation of the patients. Then the researchers checked the completeness and authenticity of the questionnaire and eliminated the invalid questionnaire. The demographic, clinical and laboratory data of patients were collected during the same period. Demographic data included age, gender, primary renal disease, diabetes mellitus and hyperuricemia before dialysis. Clinical data included duration of PD, drugs, urine output, blood pressure and body mass index. Laboratory data included hemoglobin, high-sensitivity C-reactive protein, serum albumin, serum calcium, serum phosphorus, intact parathyroid hormone, total cholesterol, triglycerides, serum sodium, serum potassium, uric acid, blood urea nitrogen, serum creatinine, residual glomerular filtration rate, and urea clearance index (Kt/V). The Charlson comorbidity index (CCI)  was usedt test. Skewed continuous variables were described as median and interquartile range, and compared by Mann–Whitney U test. Categorical variables were described as frequency and percentage, and compared by the Chi-square test. Spearman’s correlation analysis, logistic regression analysis, or linear regression analysis were used to analyze the influence factors for pain, and the relationshipbetween pain and depressive symptoms, sleep quality and quality of life. Two-sided p < 0.05 was considered statistically significant. All analyses were performed with SPSS version 16.0 .Continuous variables approximately normally distributed were described as mean ± standard deviation, and compared by independent sample n = 1, 0.7%), neck , trunk , and limbs . And 101 patients (66%) had multiple sites of pain, and 28 patients (18.3%) with pain were treated with analgesics. The causes of pain were calcium and phosphorus metabolism disorders , hyperuricemia , diabetes , senile degenerative disease , lower extremity arterial occlusion , and other reasons .A total of 463 PD patients were included in this study . The meap < 0.05) (p < 0.05)  . Binary  < 0.05) .p＜0.05)  and PSQI score , and negatively correlated with PCS score . No significant correlation was found between the score of PRI and total score of QOL  or the score of MCS . Binary Logistic regression analysis showed that the score of PRI was an independent risk factor for depression symptoms in PD patients (p = 0.015) (p = 0.044) and the score of PCS (p = 0.016) in PD patients after adjustment for other confounders  . Spearma= 0.015) . Multiplfounders  and 5. . SpearmIn this cross-sectional study, it was found that 33.1% of PD patients occurred pain symptoms. Older age and higher level of intact parathyroid hormone were independent risk factors for pain in PD patients. The score of PRI was an independent influence factor for depression symptoms, the score of PSQI and the score of PCS in PD patients.Pain was one of the common symptoms in patients with ESRD. Currently, few data on the management of pain were available in PD patients. This study found that the incidence of pain in PD patients was 33.1%, which was lower than that of HD patients (50–82%) . During This study showed that the disorder of calcium and phosphorus metabolism was the main cause of pain in PD patients, and higher intact parathyroid hormone was one of independent risk factors for pain in PD patients. Elsurer et al.  also fouA Canadian study showed that pain was independently related to depression and sleep disorders in HD patients . ElsurerA limitation of this study was that all participants were from a single PD center of Southern China. The results of this study might not be applicable to all PD patients. Another limitation was cross-sectional design of this study, which could not examine the causal relationship between pain and the potential risk factors.In conclusion, this study demonstrated that the incidence of pain in PD patients was 33.1%. Older age and higher level of intact parathyroid hormone were independent risk factors for pain. Pain was independently related to depression symptom, sleep quality and QOL in PD patients. Understanding experiences of pain in PD patients could inform strategies to address this symptom. It was suggested that pain problem of PD patients deserved more attention and a strong imperative to establish chronic pain management of PD patients as a clinical and research priority.