To evaluate the efficacy and safety of acupuncture compared to that of parecoxib sodium on postoperative pain (POP), postoperative nausea and vomiting (PONV), and the Bruggemann Comfort Scale (BCS) in patients following laparoscopic cholecystectomy (LC).  Eligible patients admitted to the hospital for LC were randomly allocated to either acupuncture or control groups in a 1 : 1 ratio. The subjects in the acupuncture group received acupuncture while those in the control group were injected by parecoxib sodium at their requests. The pain score, PONV score, and BCS were assessed at 0 h, 6 h, 9 h, and 12 h after operation. The primary outcome was the pain score. The secondary outcomes included the number of patients asking for parecoxib sodium from the two groups at 0–6 h and 6–12 h, PONV score, and BCS score. P=0.002, P=0.008). However, no difference was found at 12 h. Besides, the number of patients administered parecoxib sodium in acupuncture group was less than that in the control group both at 0–6 h and 6–12 h after operation . Similarly, there were significantly lower levels of PONV score and higher levels of BCS at 6 h after operation in the acupuncture group than in the control group. However, no difference was found at 9 h and 12 h.  The pain score of the acupuncture group were lower in acupuncture than that in the control group at 6 h and 9 h after operation . Acupuncture can clinically improve the short-term treatment of postoperative pain after LC and reduce the request for extra analgesics; therefore, acupuncture might be a potential method as one of multimodal analgesia techniques to treat POP following LC.  Laparoscopic cholecystectomy (LC), known as minimally invasive cholecystectomy , is currHowever, postoperative pain after LC remains a plague for patients, which can lead to anxiety and sleep disturbances , and eveNonsteroidal anti-inflammatory drugs (NSAIDs) are effective analgesics widely used in the postoperative surgical period. According to a systematic review, oral NSAIDs were recommended as the first line treatment for pain after LC (GRADE A), and opioids (GRADE B) were used only when necessary to avoid related side effects . Notablyβ fibers in the peripheral nervous system [Acupuncture is an important component of traditional Chinese medicine which has protected Chinese people against diseases for several millennia. In recent years, more and more evidence shows that acupuncture applied in the perioperative period can alleviate postoperative pain and reduce the use of opioids . It had s system . TherefoYet little evidence suggests the effect of acupuncture on controlling pain after LC, and thus we designed this trial to examine the efficacy and safety of acupuncture for relieving postoperative pain in patients after LC. Simultaneously, we also estimate the influence of acupuncture on postoperative nausea and vomiting (PONV) and the levels of comfort and sedation of patients.This trial was a randomized, controlled, assessor-blinded, and single-center clinical study performed at Hepatobiliary Surgery at Yueyang Hospital of Integrated Traditional Chinese and Western Medicine, Shanghai University of Traditional Chinese Medicine .This study had been approved by the Institutional Review Board of the Yueyang Hospital of Integrated Traditional Chinese and Western Medicine at the Shanghai University of Traditional Chinese Medicine. The reporting and design of the trial followed the Uniform Standards for Trial Reporting and the Consolidated Standard of Reporting Trials (CONSORT)  and StanThe patients admitted to the hospital for LC would be screened by 2 residents. All subjects were from Yueyang Hospital of Integrated Traditional Chinese and Western Medicine affiliated to Shanghai University of Traditional Chinese Medicine from 2020 to 2022 and would receive an elective laparoscopic cholecystectomy. Inclusion criteria were as follows: patients older than 18 and no more than 75 years old, patients with American Society of Anesthesiologists (ASA)  grading All eligible subjects would be randomized to one of the two groups after signing their informed consent forms.An independent statistician generated a randomization sequence by the SPSS 26.0 software. Opaque envelopes veiling the randomized number and corresponding treatment details inside were given to the subjects before they signed the informed consent forms. The acupuncturists implemented the treatments after checking the information within the envelopes. All the outcome assessors and statisticians would be blinded to the treatment details of the subjects which only the acupuncturists and statisticians who generated the randomized number knew.The procedure of the interventions and assessments is shown in The subjects in the control group who had undergone laparoscopic cholecystectomy would be administered parecoxib sodium  in a single dose, according to the actual situation.(1) Parecoxib Sodium. The acupuncture group would receive the injection of parecoxib sodium as the same with the control group when necessary.(2) Preparation before Acupuncture. Acupuncture treatments were performed by licensed acupuncturists with at least 3 years of clinical experience. All acupuncturists had received training about the treatment regimens. The acupoints chosen in this trial are shown in (3) Procedure of Acupuncture. The spines of the patients would be kept in position, and skin around the acupoints would be disinfected by using 75% alcohol. The acupuncture treatment would be given when patients returned to units within 2 hours after operation. The acupuncturists would use disposable sterile needles  to insert the skin with a depth of about 10–30 mm based on the acupoints' locations. Subsequently, the acupuncturists would manipulate the needles by twirling, lifting, and thrusting to get a sense of “De qi” . The same manipulations would be repeated for 3 times every 10 min. Needles would be removed softly and carefully for preventing bleeding or subcutaneous hematoma each time.The pain score on visual analog scale (VAS) : Pain inThe number of patients who asked for analgesic: In this trial, parecoxib sodium would be given to the patients at their requests, and we recorded the number of them at 0–6 h and 6–12 h after LC.The PONV on VAS score : PONV scBruggemann comfort scale (BCS) : BCS wasThe incidence of adverse events (AEs): Adverse events and corresponding managements would be recorded on case record form (CRF). The relationship between the AEs and interventions would be confirmed by specialists and acupuncturists. The common AEs would include needle sticking, dizziness or syncope, bleeding, the occurrence of subcutaneous hematoma, severe pain, infection, and allergy.α = 0.05 (two-sided) and 1-β = 0.80, z0.05/2 = 1.96, z0.2 = 0.84 and calculated n = 18, and considering an attrition of 15% in total of 42 subjects were required.The sample size was calculated based on the changes of pain scores. The sample size was estimated based on the change in pain score on VAS at 6 h after operation. Referring to the study results of An et al. , the meaP < 0.05 (two-tailed) was considered statistically significant. Enumeration data were described by frequency or percentage and tested by χ2 or Mann–Whitney U rank sum test. Measurement data were described by means ± SD or medians . Student's t-test, multivariate analysis of variance and Mann–Whitney U rank sum test was used for the between-group comparisons.An independent statistician blinded to the allocation of the subjects analyzed all the data by SPSS 26.0. The outcome assessors were trained before the trial and would begin to record the patients' information and the results of observed indicators on the CRF after each visit. To ensure the accuracy, two researchers are separately responsible for entering the data extracted from the CRFs into Excel. The personal and hospitalization information of the subjects, including name, age, gender, ID, and telephone number, as well as surgery details would be confidential.Experts in surgery, acupuncture, anesthesiology, statistics, and methodology were involved in the development, review, and revision of this study protocol. Specified introduction and training were given to different participants involved in the trial, such as patient recruitment, communication techniques, completion of the CRF, interventions, data management, and analysis. Any reason for discontinuation of the trial would be recorded in the CRFs.60 were eligible for the inclusion criteria, of whom 18 were excluded due to failures in further screening. 42 participants were randomly assigned to either the acupuncture group or control group with 21 for each. Finally, a total of 42 subjects were analyzed .In P=0.002, P=0.008). There was no difference observed at 12 h between the two groups (P > 0.05).Both the pain scores on VAS decreased in the two groups after their treatments . Pain scP=0.019, P < 0.001)  .P=0.004). However there was no difference in PONV score was found at 9 h and 12 h (P > 0.05).PONV scores in the two groups decreased after their treatments . PONV scP=0.007). However, there was no difference in BCS score was found at 9 h and 12 h (P > 0.05).The results of BCS are shown in During the study, 3 subjects experienced bleeding after removing the needles but that lasted for less than 30 seconds with no discomfort, and 2 subjects had subcutaneous hematoma after bleeding. Besides there is no severe adverse events related to acupuncture and parecoxib sodium .To our knowledge, this RCT was the first to explore the effectiveness of an acupuncture treatment regimen aimed at POP in patients after LC both subjectively and objectively. We found that acupuncture can help relieve POP, especially in a short period after LC, and reduce the number of patients required for extra analgesics. Moreover, acupuncture can also improve the comfort levels of patients and alleviate their PONV. The results of this trial supported that acupuncture might be an adjunctive method for the initial management for LC.2 pneumoperitoneum during the surgery [With the advancement of techniques, laparoscopic cholecystectomy has gradually replaced traditional open cholecystectomy in most occasions  and been surgery . Since tAcupuncture is one of the most ancient medical treatments. Acupuncturists treat diseases by inserting needles into the meridians and acupoints on the skin with certain manipulations. The analgesic effect of acupuncture has drawn much attention, and numerous studies about it have been conducted since the 1970s. There are more than 80 recommendations related to acupuncture in about thirty-nine guidelines by the National Guideline Clearinghouse (NGC), of which 49 explicitly recommend acupuncture for medical practice and 37 (75.51%) are about the treatment of painful conditions by acupuncture . What meAccordingly, we designed this study to examine the efficacy of acupuncture in treating postoperative pain compared to that of parecoxib sodium recommended by clinics for patients following LC by comparing the VAS scores of pain and the proportion of patients asked for parecoxib sodium. In addition, we also examined the effect of acupuncture on PONV and levels of comfort.The acupuncture protocol in this trial was based on the theory of TCM and clinical experience. In the theory of acupoints, “Jing-river Points” is a generic term of Jing, Xing, Shu, Yuan, Jing, and He points of each meridian, describing meridian Qi as water flowing from small to large. GB 41 is the Shu point of the gallbladder meridian, while GB 34 is the He point. Shu point has a good effect on pain conditions, and He point is mainly used for treating diseases of Zang-fu organs. So, we chose the GB 41 and GB 34 to treat the pain following LC. TE 5 is the Luo point that connects the triple energizer meridian and gallbladder meridian, and both TE 5 and LI 4 are commonly used to manage pain and postoperative nausea and vomiting which might be related to the stimuli-specific cortical networks , 26.In this study, we measured the pain intensity with a VAS. There was a significant reduction in pain score in the acupuncture group compared with the control group at 6 h after operation, although no difference was found in rescue analgesia between the two groups in 0–6 h after operation, indicating that acupuncture might have an extra analgesia effect compared with rescue analgesia. And the effect of acupuncture lasted until 9 h after operation, as the VAS of pain score was still lower in the acupuncture group than in the control group. However, there was no significant difference between the two groups in pain score at 12 h after operation. On the one hand, the request of rescue analgesia in the control group was higher compared to the acupuncture group in the 6–12 h after operation that might minimize the difference of pain score between the two groups. On the other hand, the pain score in both groups was less than 3 points which means minor pain that can be tolerated implying that the analgesia effect of acupuncture was comparable to the parecoxib sodium in the 6–12 h after operation.Besides, the pain score decreased by 3.81 points at 12 h after operation. It has been reported that a reduction of 2 points in the VAS score reflected satisfactory pain relief in patients after surgery . Our resIn terms of extra analgesics, the proportion of patients required for parecoxib sodium in the acupuncture group was smaller than that in the control group at 0–6 h and 6–12 h after operation in our study. The need for additional analgesics has been reported to vary widely among individuals following LC, with approximately 10–30% of the patients requiring no additional analgesics . Our stuPONV might be related to the trauma of surgery and anesthesia, as well as the analgesia. We found that the PONV score in the acupuncture group was lower than that in the control group at 6 h after operation. In a systematic review, acupuncture along with and after tonsillectomy can reduce the incidence of PONV in the acupuncture group compared to the control group . StoiceaThis study had some limitations. Firstly, there was an absence of a sham acupuncture group as the control group. This trial aimed to examine the efficacy and safety of acupuncture for postoperative pain by comparing it to that of parecoxib sodium, so we did not set up the sham acupuncture group. Secondly, we performed acupuncture after the patients returned to the units, resulting in a time difference for completing acupuncture treatment between patients. To deal with this problem, the acupuncturists were asked to come to the units and implement acupuncture as quickly as they received the information within 2 h after operation. Thirdly, the observation time was limited, and no follow-up investigation was involved after the discharge. Thus, the long-term analgesic effect of acupuncture and the optimal acupuncture frequencies remain unknown. Fourthly, this was a single single-center trial, and the sample size was small that might introduce potential biases. Despite this, the outcomes of this trial will be used to guide a better design including multicenter and sample size calculation for a further randomized controlled trial. Finally, all the patients in the acupuncture group received the same standard regimen of acupuncture; however, semistandard regimen which is one of the features of TCM was more widely used in clinics . In the The results of this trial serve as clinical evidence supporting the fact that acupuncture is safe and provides a short-term analgesic effect for patients following LC at least in the 12 h after operation. Overall, our paper suggests that acupuncture might be a potential method as one of the multimodal analgesia techniques to deal with POP following LC.


The study aimed to explore the influence of genetic polymorphisms in ANKK1 andDRD2 on the signs and symptoms of temporomandibular disorder (TMD) inconstruction workers. This cross-sectional study included only male subjects.All construction workers were healthy and over 18 years age. Illiterate workersand functionally illiterate workers were excluded. The diagnosis of TMD wasestablished according to the Research Diagnostic Criteria for TMD (RDC/TMD).Genomic DNA was used to evaluate the genetic polymorphisms ANKK1 (rs1800497) andDRD2  using Real-Time PCR. Chi-square or Fisher exact tests wereused to evaluate genotypes and allele distribution among the studied phenotypes.The established alpha of this study was 5%. The sample included a total of 115patients. The age of the patients ranged from 19 to 70 years . Chronic pain (87.7%), disc displacement (38.2%), andjoint inflammation (26.9%) were the most frequently observed signs and symptoms.The genetic polymorphism rs6276 in DRD2 was associated with chronic pain(p=0.033). In conclusion, our study suggests that genetic polymorphisms in DRD2and ANKK1 may influence TMD signs and symptoms in a group of male constructionworkers. The temporomandibular joints (TMJs) play crucial roles in mastication and jawmobility, and verbal and emotional expression. Temporomandibular disorders (TMDs)include several disorders that can lead to orofacial pain symptoms ,,,,,,,,The American Academy of Orofacial Pain introduced genetic factors as etiologicalfactors associated with TMD in 2008. After this study, some studies in differentpopulations and evaluating a variety of genes and pathways were performed. Asystematic review from Visscher and Lobbezoo This cross-sectional study was executed in the Dental Clinic of the SocialService of the Civil Construction Industry Union of the Paraná State(SECONCI-PR), which is a state located in the south of Brazil. SECONCI-PR is anon-profit organization, linked to the Employer's Union of the CivilConstruction Industry of Paraná that represents companies in the sector. Theorganization aims to promote health and safety at work for the constructionworkers in the region.All the participants signed an informed consent form, and interviewers recordedtheir personal data after their approval. The study protocol was approved by thelocal Human Research Ethics Committees approved this study (number #2.802.708).The construction workers were consecutively included from 2018 to 2019. TheAssociation study (STREGA) statement checklist was followed to develop andreport the results of this study  Illiterate and functionally illiterate workers, those who were unable tounderstand and express themselves in written form, were not included. Women wereexcluded from this study. All construction workers were healthy adult males(older than 18 years old), that did not report to use analgesic medication orantibiotics in the past 6 months. The sample was composed only by workersemployed in the physical construction.During the patient’s dental appointment, they were invited to participate in theproject and answered the questionnaire. A senior dentist who had experience withTMD and was also trained and calibrated for diagnosis according to criteria ofAxis I of the Research Diagnostic Criteria for TMD (RDC/TMD) performed theclinical examination. Axis I diagnose three groups of disorders: myofascial pain(with or without mouth opening limitation), disc displacements, and inflammatoryconditions. Disc displacements by evaluated by side (left and/or right) with orwithout reduction. Inflammatory conditions were evaluated by side (left and/orright) and classified in arthralgia, osteoarthritis, and osteoarthrosis.The RDC/TMD Axis II was filled by the patient to measure the pain intensity andthe depressive symptoms levels. Chronic pain was graded from 0 to IV . Depression, Nonspecific Physical Symptoms IncludingPain (NPSIP), and Nonspecific Physical Symptoms Excluding Pain (NPSEP) wereclassified as low, moderate, or severe.Saliva samples from all included patients was also collected during the dentalappointment and stored at -20ºC. The genomic DNA was extracted from the cells inthe saliva using a method previously described was performed The selection of the studied genetic polymorphisms was based on their previousassociation with pain phenotypes. Therefore, one genetic polymorphism ANKK1(rs1800497), and two genetic polymorphisms in DRD2  wereinvestigated. The characteristics of the selected genes and geneticpolymorphisms are presented in The Chi-square test was used to calculate the Hardy-Weinberg equilibrium.Chi-square test or Fisher exact test were used to evaluate genotypes  and allele distribution among thestudied phenotypes. Statistical analysis was performed using Epi info 7.1 usingan alpha of 5% (p<0.05).The sample included a total of 115 male patients aged ranging from 19 to 70 years old. The flow chart of the patient’sscreening is present in All the genetic polymorphisms assessed were within the Hardy-Weinberg equilibrium.TMD is an important public health problem that affects between 5 to 12% of thepopulation and is classified as the second most common musculoskeletal disease afterchronic low back pain, resulting in pain and disability A large cooperative agreement study called OPPERA  evaluated the association of genes involved in painprocesses with TMD. The majority of the genetic polymorphisms had strongerassociations in women compared to men, but due to the smaller sample size of malesthe authors considered it inconclusive whether this trend is indicative ofsex-specific genetic effects Dopamine could cause joint pain processes, local sensitivity, and reflex activitydeveloped by the muscles of mastication The studied genetic polymorphism in ANKK1 was associated with myofascial pain. Aprevious study demonstrated that the rs1800497 polymorphism in ANKK1 is functionaland can reduce the expression of the dopamine receptor DRD2 In our study, we used "Research Diagnostic Criteria/Temporomandibular Disorders"(RDC/TMD) instrument to diagnose TMD, which is a widely used tool in TMD research.This tool standardized the assessment and classification of patents. It is based onthe biopsychosocial model of pain The idea is that other relevant patient characteristics that may influence the TMDOur study suggested that genetic polymorphisms in DRD2 and ANKK1 might influence TMDsigns and symptoms in a group of male construction workers. More studies arenecessary to confirm our findings.


Neck and back pain afflicts millions of people. Magnetotherapy has shown to have anti-inflammatory effects that could act on pain generation, but the literature lacks provide a precise therapeutic protocol.A high-intensity electromagnetic field with a dedicated applicator was administered to 38 patients with low-back pain and 30 patients with neck pain. The device provides 60 mT and a frequency of 50 Hz for 30 minutes, the session was repeated 4 times.The mean VAS of the low-back pain group decreased from 6.56 to 4.54, with a significant reduction of 30.8%. The mean VAS of the neck pain group decreased from 6.51 to 1.96, with a significant reduction of 69.9%.The treatment used showed good results in both groups of the patient, without side effects. The therapeutic protocol adopted is safe, provide rapid relief from the pain and is not time demanding. This treatment could represent an effective non-pharmacologic physical therapy option in the treatment of low-back pain and cervical pain. Neck pain and low back pain are the most common symptoms These conditions are a significant medical problem and are the principal cause of work absences in industrialized societies A widely used technology for the non-invasive treatment of musculoskeletal disorders is pulsed electromagnetic fields (PEMF). PEMFs are selected low-frequency electromagnetic fields without ionizing or thermal effect 2.2.1.Sixty-eight subjects , out of 120 patients screened, between 27 and 89 years old were enrolled in this open study: 38 patients  with low back pain, and 30 patients  affected by cervical pain. Inclusion criteria were: neck or back pain since more than three months; degenerative changes of one or more intervertebral disc documented by magnetic resonance imaging in the last year, according to the CTF (Combined Task Force) classification The treatment with the high-intensity low-frequency electromagnetic field lasted for 30 minutes, was repeated four times with a mean interval of 26 hours (+/−2). The applicator of the device was positioned directly on the painful area .Each patient quantified the painful symptoms on a Visual Analogue Scale (VAS); the scale was graded from 1 (minimum pain) to 10 (maximum pain intensity). Measurements were taken 30 minutes before the first treatment and 24 hours after the last treatment. No other therapy was performed during the study period. Patients are encouraged to conduct the normal activity of daily living. The only rescue medication approved was Paracetamol 500 mg, and its intake was recorded.2.2.The station consists of two parts. One is connected to the electricity grid (220 V at 50 Hz) and reduces the electric current from 220 V to 60 V. The second part is the electromagnetic fields generator that consists of a coil formed by a winding of enamelled copper wire, with dedicated number of turns N, arranged around the central leg of an E-shaped beam of iron-silicon laminas of the type usually used in transformer consoles. The magnetic circuit is not closed as the complementary side of the transformer joins the three rods of the E only on one side while the other side remains open.The polar expansion in the middle measures 33 mm × 38 mm while the side ones, 16 mm distant from it, measure 17 × 38 mm .The rods of the E act as polar expansions that operate as a triad of electromagnets in which the control unit has always an opposite polarity than the lateral rods. The device label is CE1370.The winding is powered at 60 V with alternating current at a frequency of 50 Hz, with an intrinsic resistance calculated so that Ohm's law is always satisfied. The intensity of the relative current is 0.8 A. The magnetic flux density or the magnetic induction, measured with a Hall probe  in contact with the expansion in the middle, is 60 mT. Considering the distinctive geometrical conformation of the rods that generate the field and the consequent spatial distribution of the relative flow lines, the electromagnetic forces induced in the tissues produce activity in a large area of the body.2.3We calculated the VAS score means (±standard deviation) for both groups before and after the treatment. The mean reduction in pre- and post-treatment VAS pain intensity was assessed with the one-tailed Student's t-test for paired data, as the Kolmogorov-Smirnov test excluded a significant deviation from normality of VAS changes. The minimum sample size was determined to have an intermediate Cohen's effect size of 50%, a power of not less than 80% and a significance of 95%. It was 27, properly lower than the smallest group of 30 patients with neck pain.G*Power software, version 3.1.9.4, and SPSS software, version 10,  were used to perform sample size analysis, and descriptive and inferential statistical analyses, respectively. A p-value <0.05 was assumed to assess the significance of all statistical testing.3.The affected intervertebral disc and the recorded pain perceived before and after the treatment according to a visual analogue scale are summarized in In In All patients in the two groups, low back and cervical pain, reported a significant and rapid improvement in subjective pain. Three subjects in the cervical and two in the low back groups took one tab of the rescue medication (paracetamol) after the first session of the electromagnetic fields.Every subject of both groups completed the short therapeutic cycle without side effects that may have required suspension or cessation of the treatment.4.Musculoskeletal system disorders (MSDs) are the most commonly encountered disease in orthopaedics and physiotherapy practice in the world. Low back pain, in particular, is the most prevalent presentation with long abstention from work and high economic losses. Chronic cases with a pain history longer than 12 weeks are the most difficult to treat. Therefore, it is crucial to establish new effective and nonsurgical treatment modalities that guarantee minimal side effects.Our observational study provides reliable evidence that a high-intensity electromagnetic field with a dedicated probe is very effective for neck and low back pain treatment. Each patient in the present open clinical study reported a prompt, rapid and almost complete regression of local pain within four sessions of 30 minutes each.The magnetic field that we have applied to our group of patients has been able to interfere with the pro-inflammatory mechanisms in the appearance and persistence over time of the painful symptoms. The effects of the electromagnetic field on the inflammatory cascade were previously studied with the use of fixed frequency magnetic fields (ELF) and with variable over time magnetic fields (TAMMEF) also in other diseases characterized by chronic pain Moreover, the non-invasiveness and well-tolerability of our technique made it applicable in a vast cohort of patients, as demonstrated by the great age range of the people that we had treated, between 27 and 87 years. Even patients with co-morbidities like gastric, hepatic or renal pathologies, have been safely treated.This study has some limitations. It lacks a control group with a shame therapy, but the positive effects of magnetotherapy with validated parameters are well documented, hence we haven't found it productive to divide patients. Another bias is the absence of a longer follow-up to evaluate the possible relapses. Further studies are needed to assess also the impact of the therapy on physical activity and the activity of daily living.5.In conclusion, these results suggest that the treatment with high-intensity low-frequency magnetic fields reduces pain and disability in patients suffering from non-specific low back pain and cervical pain. This treatment could represent an effective non-pharmacologic physical therapy option for these patients, but prospective controlled blinded trials are needed to confirm and validate our results.


Chronic musculoskeletal pain (CMP) is characterised by pain related to the muscles or the joints with a duration of three months or more and is associated with high symptomatic burden in patients in primary health care. CMP is commonly associated with impaired mental health, which may affect the rehabilitation process. The primary aim of this study was to compare symptoms of anxiety, depression, fatigue, and insomnia in patients in primary health care with and without CMP. The secondary aim was to assess difference in mental health symptoms related to number of pain sites and pain intensity.This cross-sectional study was conducted in Trondheim, Norway. All patients aged 21–58 from randomly selected general practitioners (GPs) were invited to participate. Participants were classified into two groups according to presence of CMP. Symptoms of anxiety, depression, fatigue, and insomnia were assessed by the Hospital Anxiety and Depression Scale (HADS), Chalder Fatigue Questionnaire (CFQ), and Insomnia Severity Index (ISI), respectively, using an online survey system.p < 0.01 compared to no-CMP patients. Symptoms of impaired mental health increased with increasing number of pain sites and pain intensity (p < 0.001).From the patient lists of six GPs, we included 969 patients. Mean age 46 years (SD: 10.1), and 517 reported CMP. CMP patients reported higher mean symptom score for anxiety (5.4 vs 3.7), depression (3.4 vs 2.0), fatigue (14.2 vs 11.2), and insomnia (8.1 vs 4.4), all Primary health care patients with CMP reported significantly more symptoms of anxiety, depression, fatigue, and insomnia than patients without CMP. The higher number of pain sites and pain intensity, the more mental health symptoms, especially of anxiety. Primary health care personnel have to address mental health issues when treating patients with CMP.Clinicaltrials.gov . Musculoskeletal pain is the most prevalent cause of disability worldwide , 2, and CMP in combination with reduced physical function is associated with increased risk of mental health issues, such as fatigue –11, sleeNon-musculoskeletal pain symptoms as reduced work capacity, and impaired social life represent independent predictors of quality of life among CMP patients , 28. In We have previously published findings on reduced health-related quality of life in a CMP group compared to a no-CMP group in a group of unspecified patients in the primary health care system . In thisThis is a cross-sectional study based on data collected from patients of GPs in Trondheim County, Norway. The data was collected in a randomized controlled trial (RCT) conducted in the period from November 2013 to July 2015. The RCT aimed to investigate patients in primary health care clinical practice; identify CMP, and to compare the effect of systemized collaboration between GP’s and physiotherapist on sick leave and referral to special health care. The focus in the present study is to compare mental health symptoms among patients in primary health care with and without CMP. The study was performed at the Department of Public Health and Nursing, Faculty of Medicine and Health Sciences, Norwegian University of Science and Technology (NTNU), Trondheim, Norway.About 211 106 citizens lives in Trondheim municipality (2022), which is the fourth largest city in Norway. Among 162 general practitioners in Trondheim municipality, we randomly invited 20 to participate in the study. The 20 GPs were randomly selected using a computer random number generator, developed and administrated independently by the Unit for Applied Clinical Research, Norwegian University of Science and Technology (NTNU), Trondheim, Norway. GPs were stratified by gender before the randomization to prevent possible bias related to differences in the GPs’ patient populations. We used postal mail and telephone to invite GPs to participate in our study. To ensure rural GP representation, two additional GPs  were selected due to experience with interdisciplinary collaboration in primary health care, invited, and accepted our invitation to participate in the study.We invited all patients registered on the participating GPs’ patient lists aged 21 to 58 years to participate in the study. In the original study, the main aim was to explore sick-leave in a working population during a three-year period from inclusion. In Norway, most adults younger than 21 are in full-time education and many have the opportunity of early retirement at the age of 62 years. Thus, aiming for enrolment of a population most likely to be working throughout the study period, the age range 21 to 58 years was chosen. Except from this, our study included no exclusion criteria. Eligible patients received study information and invitation to participate by postal mail. The patients accepted the invitation by replying to the invitational letter in writing, by phone, or by completing the web-based questionnaire by logging in to the online survey system .The data in this study was collected by self-reported questionnaires using an online system (CheckWare®) sent to the participants registered private email account. The participants had to complete the questionnaires within one month, if not, an automatic reminder was sent. Patients were classified with CMP if reporting “pain and/or stiffness related to the musculoskeletal system, with continuous duration of at least 3 months during the last year”.Subject characteristics, including gender, age, marital status, education, occupational activity, sick leave, grade of social benefits, and bodily pain were self-reported by study participants at study entry using the online survey system. Questions regarding pain sites and pain intensity were included in the same questionnaire, but these questions were only available for the subjects reporting CMP. The questions regarding pain sites and pain intensity were highlighted to relate to the episode(s) of CMP, not necessary to the time point of answering the questionnaire. Pain characteristics used in the current study were assessed by questions based on the “SF-36 Health Survey ” , 34, theWe assessed symptoms of anxiety and depression, referring to the last week, by the Hospital Anxiety and Depression Scale (HADS) . HADS isWe assessed fatigue by the Chalder Fatigue Questionnaire (CFQ) . The CFQSleep disturbances were assessed by the questionnaire Insomnia Severity Index (ISI) . This quThis study was approved by The Regional Committee for Medical and Health Research Ethics in Central Norway (2012/1232), and our study procedures followed the Helsinki Declaration. All participants completed an informed consent before they entered the study and the online questionnaires. All participants who participated in our study were part of a prize draw for a gift card worth 500 NOK.p-value.Patient characteristics, comparisons of self-reported symptoms of anxiety, depression, fatigue and insomnia between patients with and without CMP were analysed by independent samples t-test for continuous variables, Fisher’s Exact tests for categorical variables, Pearsons Chi-square test for dichotomous variables, and Mann–Whitney U-test for ordinal variables. Normality of the continuous data was assessed by Shapiro–Wilk. The results (observed data) are presented as number (n) and percentages (%) or means and standard deviation (SD) as appropriate. Differences between the groups are presented in mean difference and 95% confidence interval (CI) and Differences in symptoms between the various sub-groups of pain sites and pain intensity were assessed using a Kruskal–Wallis one way ANOVA, adjusted for the Bonferroni correction for multiple tests. Due to outliers, we log transformed the data by using the function Log10 before the ANOVA analyses were performed. Missing data was handled by listwise deletion, thus only observed data were included in our analyses.p-values < 0.05 as statistically significant. The statistical analyses were conducted using IBM SPSS Statistics version 27.The current study is based on an RCT, thus no sample size calculation was performed for the thesis included in this paper. We considered In total, six GPs agreed to attend our study. Among the twenty GPs invited to the study, four agreed to participate , in addition to the two invited GPs from rural area . Study flow chart is presented in Fig. Patient characteristics is presented in Table The total group of patients included in the current reported a overall good mental health. However, when comparing symptoms between the CMP patients and the no-CMP patients, the patients who reported CMP reported significantly more symptoms of anxiety, depression, fatigue and insomnia Table , and morThe most frequently reported mental health issue in both groups was insomnia. Almost half of the CMP patients reported sleeping problems compared to one in four of the patients without CMP. A significantly higher amount of CMP patients (16.4%) than patients without CMP 2.1%) reported sleeping problems corresponding clinical insomnia (Table .1% reporAmong CMP patients, we found that patients with high number of pain sites reported significantly more symptoms of anxiety, depression, fatigue, and insomnia, compared to the patients with fewer pain sites Table . This teFor the CMP patients, the higher pain intensity, the higher mental health symptom levels were reported Table . A markeIn this cross-sectional study among patients of general practitioners in primary care, just over half reported CMP symptoms. The majority of the included study participants reported good mental health, with few cases indicating clinical disorders. However, patients with CMP reported significantly higher symptoms on all the studied mental health issues compared to patients without CMP. Symptoms of anxiety, depression, fatigue, and insomnia increased with increasing number of pain sites and pain intensity. Within the sub-groups of number of pain sites and pain intensity, a larger amount of patients reported symptoms representing risk of developing clinical anxiety, with increasing number of pain sites and pain intensity.Our major strength is our study population. We have assessed an unspecified group of CMP patients in general health practice with no exclusion criteria related to type, duration or severity of CMP to highlight the general symptomatic multifactorial burden this group is representing. In the current study we categorized patients with CMP complaints regardless of pain site in order to explore common mental health symptoms in these patients. Our results may therefore present a picture of mental symptoms for these patients overall. Although the results cannot be directly generalized to site-specific CMP complaints, it is well documented that prognostic factors are shared among the different complaints , 26. ThuThere are some limitations in our study. Firstly, by using a cross-sectional design, we are not able to claim causality or certain relationship between CMP and symptoms of impaired mental well-being. Secondly, a high proportion of the GP’s contacted declined to participate in our study, and we have no information on their reason for non-participation. There is a possibility of these general practitioners not fully representing the general group of practitioners in Trondheim county. Perhaps did we include general practitioners with a high amount of patients with CMP or with a special interest and awareness of this patient population. Only 23% of the eligible patient population agreed to participate, which may introduce selection bias into our study, and thus reduce the generalizability of our findings. Thirdly, like most observational studies, the use of self-reported information may introduce some bias to the material. There are individual, social, and cultural differences in how CMP, pain, fatigue, insomnia, anxiety and depression is evaluated and perceived. Although the factors assessed in the current study, symptoms of anxiety, depression, fatigue and insomnia, are highly dependent on subjective perception, they are important prognostic factors and relevant for proper management of these patients in clinical practice.Another important limitation is that the CMP patient group could have experienced CMP at different time points during the past year, however the questions regarding mental health referred to the last week or month. Therefore, patients with CMP several months ago may not report any reduced mental health symptoms in present time although they could have been present at the time of CMP. Another limitation is the heterogeneity of both the CMP group and the group without CMP. The patients in the CMP group consists of both patients with current CMP at the time of fulfilling the questionnaire, while others in this group may be quite free of symptoms after experiencing CMP several months ago. This aspect will clearly affect the CMP group reports of mental health symptoms and information recalling. Further, it is likely that subjects in the no-CMP group could have experienced CMP previously and may still experience both somatic and metal symptoms caused by this disorders when reporting to our study. Patients invited to the study were informed that the objective was to address CMP. It is therefore perceivable that we recruited a higher proportion of patients with CMP than patients without CMP among the GPs’ patients. No sample size calculation was performed for the current study.We found in our study that the patients with CMP reported significantly more symptoms of anxiety and depression compared to the patients without CMP. These results are supported by a number of previous studies reporting a higher risk of developing anxiety and depression among patients with CMP –47. In tFatigue has been associated with severe and prolonged health disorders , and theInsomnia is common among patients with CMP. Insomnia has been identified as a contributor to chronic pain, and perceived pain intensity in particular –14, 22. The mental health and pain-related outcomes included in our study share common risk factors. Insomnia and symptoms of depression are found to increase the risk for developing CMP , and to Our findings show that patients in general practice with CMP are considerably more burdened by different mental health related issues than patients without CMP. Increased awareness of the complexity of CMP and its relation to impaired mental health is important for primary health care personnel in order to provide appropriate patient management. The observed increase in levels of mental health symptoms with increasing pain intensity and number of pain sites highlight the importance of the primary health care system establishing effective strategies for managing mental health issues among patients with CMP, and particularly for patients with high pain symptom levels.Our study aimed to include a general group of primary health care patients, representing the working population, and included few inclusion criteria. Although, it is possible that a rather high number of patients who volunteered for participation compared to the general population have experienced musculoskeletal pain, due to this being a study on chronic musculoskeletal pain. However, patient demographic characteristics of our study indicate that especially the present CMP population to be representative for the general Norwegian working population’s use of the primary health care system due to musculoskeletal complaints , 48, 56.Among patients in primary health care general practice, we found that patients with CMP reported more symptoms of anxiety, depression, fatigue and insomnia compared to patients without CMP. Higher number of pain sites and increased pain intensity were related to more symptoms of impaired mental health, especially insomnia and borderline anxiety. In terms of impaired mental health, pain intensity differentiated the pain subgroups more than number of pain sites. Our findings underscore that the burden of CMP also involves multiple aspects of mental health, implying that health care personnel need to pay attention to mental health issues in the management of CMP patients. Clinical management of this patient group should not be limited to somatic pain and limitations in physical function, but also raise awareness for potential mental health issues affecting the rehabilitation process.


Patients undergoing limb amputation (LA) or limb‐sparing (LS) for lower extremity oncologic diagnoses are at similar risk for chronic postsurgical pain of neuropathic nature (CPSP/NP). Regional anesthesia (RA) techniques are pre‐emptive measures to prevent the occurrence of the CPS/NP. However, recommendations for epidural (EP) versus peripheral nerve blocks (PNBs) lack in pediatric literature.This study investigates the incidence and duration of CPSP/NP and describes NP‐directed regimens.p = .11). The rate of pain relief at any instant after the EP was 1.2 times that after PNB (p = .3). The rate of pain relief for LS with EP was 1.9 times that of pain relief for LA with EP, a statistically significant difference (p = .03). Gabapentin was used (94.5%), with addition of amitriptyline (24.2%) and both amitriptyline and methadone (12.7%).Data on demographics, use of EP or PNB, duration of CPSP/NP, and NP‐directed medication were retrospectively collected for LA and LS between 2009 and 2019. Mixed effects logistic regression was used to compare the odds of CPSP/NP between EP and PNB. Cox PH model with adjustment for clustering due to multiple surgeries on patients was used to quantify rate of pain relief between surgery groups (LA vs. LS) and RA groups (EP vs. PNB). The incidence of CPSP/NP was 36 (23.8%) after 165 surgeries (150 patients). The odds of CPSP/NP after PNB were 2.5 times those of CPSP/NP after EP (The LS with the EP group had a significantly higher rate of relief of CPSP/NP than LA with EP. Odds of CPSP/NP after PNB were 2.5 times those of CPSP after EP. Although LS procedures are generally favored due to higher functional outcomes, both procedures elicit neuropathic pain (NP) of comparable incidence and duration.Predictive factors in the development of CPSP include presurgical pain intensity, child/parent psychosocial factors, and severity of acute postoperative pain.In this study, we retrospectively studied the associations between RA (EP or PNB) and the incidence and duration of CPSP/NP after LS and LA/disarticulations for lower extremity malignant tumors. The specific aims were to characterize pain outcomes including the prevalence and probability of CPSP/NP, the duration of CPSP/NP (days), and the NP‐directed medications , as doses (mg/kg/day), and duration (days).2With approval from the Institutional Review Board, all the patients who underwent LS or LA disarticulation surgery for lower extremity malignancies between January 1, 2009, and July 1, 2019 were included in this single‐institution retrospective review from St. Jude Children's Research Hospital . Data pertaining to all their surgeries, either LS, or LA, were eligible for analysis; therefore, each patient may have contributed with data pertaining to several sequential surgeries in the LS and LA categories. There were no exclusion criteria in this retrospective study design. Data collected included demographic characteristics , oncological diagnosis, surgical procedure, type of RA, and long‐term pain outcomes. Types of RAs included EP continuous infusion, continuous PNB, and single‐dose PNB. Intra‐anesthetic records, surgical records, and nursing intraoperative records were compared to ensure data accuracy.Data on pain outcomes were collected from pain service notes and included the following: (1) duration (days) of postsurgical pain that met characteristics of NP, (2) duration (days) of therapy for each line of NP‐targeted medication, and (3) initial and maximum dose (mg/kg/day). Descriptors used to characterize NP included tingling, burning, shooting, “pins and needles,” and phantom limb pain (PLP). The NP‐directed medications included gabapentinoids , tricyclic antidepressants (amitriptyline), and methadone. The NP treatment follows an institutional algorithm that escalates medications in successive “layers” of gabapentinoids, tricyclic antidepressants, and methadone, based on tolerance and analgesic efficacy. Pain was considered resolved if all NP medications were weaned without recurrence of NP symptoms. Patients were considered lost to follow up due to transfer of care to another institution, death before complete resolution of the pain, or weaning off NP‐targeting medications, or due to missing documentation to support the resolution of NP. The pain outcomes were compared between groups treated with EP and PNB.If a patient underwent a subsequent surgery while ongoing treatment for postsurgical NP , pain outcomes were attributed to the subsequent surgery. Patients with CPSP/NP were defined as being treated postoperatively with NP‐targeted lines of medications for longer than 90 days.2.1Descriptive statistics were reported as frequency (percent) and mean (SD). Duration of CPSP/NP was calculated as the time from surgery to complete resolution of NP and absence of NP‐directed medications.p < .05 were considered significant.The rate of pain relief at any instance was compared between EP or PNB groups and between surgery (LA or LS) and treatment (EP or PNB) combination groups, using the Cox PH model with adjustment for clustering due to multiple surgeries on patients. CPSP/NP was defined as postsurgical pain of duration more than 90 days, and mixed effects logistic regression was used to compare the odds of CPSP/NP between RA groups. All the analyses were performed in R (version: 3.6.2). All 33.1Of 172 surgeries performed for LS, LA, or disarticulation during the study period, 7 were excluded due to missing data and 165 surgeries (150 unique patients) contributed to data analyses. The study included 86 (57.3%) males; mean (SD) age 12.5 (3.9) years; 112 (74.7%) White. One hundred thirty‐seven (91.3%) patients underwent one, 11 (7.3%) underwent two, and two (1.3%) underwent three surgeries . A RA technique was utilized intraoperatively and postoperatively in 162 (98.2%) of LS and LA disarticulations surgeries. Ninety‐four (57%) surgeries were completed with PNB (91 continuous infusions and 3 single dosing), 68 (41.2%) were completed with EP, and 3 (1.8%) had none. Forty‐four (26.7%) patients had LA and 120 (72.7%) had LS surgeries. Twenty‐six (15.8%) patients had LA with EP, 42 (25.5%) LS with EP, 16 (9.7%) LA with PNB, 77 (46.7%) LS with PNB, and 4 (2.4%) patients did not have information regarding RA and surgery type combination (Tables 3.2p = .11). Odds of having CPSP/NP after PNB were 2.5 (0.8–7.9) times the odds after EP. No difference was found in pain relief between EP and PNB groups (p = .3). Rate of pain relief at any instance in the EP group was 1.2 times that of the PNB group. There was a difference in the rate of pain relief between LS with EP and LA with EP (p = .03); rate of pain relief in LS with EP was 1.9 times that in LA with EP. Among all 165 surgeries, mean (SD) number of days patients had postsurgical pain/NP were 60.8 (61.1) overall, 66.6 (60.7) in PNB group, and 54.7 (62.1) in EP group . Thirty‐six 23.8%) surgeries resulted in CPSP/NP. No difference was found in odds of CPSP/NP between EP and PNB  surgeries (Table .5% surgeMean (SD) number of days patients received gabapentin in the PNB group was 69.3 (60.9), and in the EP group it was 56.6 (62.5) (Table Mean (SD) initial dosage (mg/kg/day) for gabapentin was 16 (6.7) in the PNB group, and 18.3 (11.7) in the EP group , in the context of history of disease or lesion of the nervous system.Furthermore, we described the odds of CPSP/NP following PNB as being 2.5 times that of pain following EP, and the rate of pain relief in the EP group as being 1.2 times that of the PNB group . A statistically significant difference was found between the rate of pain relief in the LS with EP and LA with EP groups, with twice as high the rate of pain relief in the LS with EP group. The fact that LS with EP had the shortest duration of pain (29 days) may suggest better prognosis of pain relief over time with EP as a favored modality for LS. We reported a lower incidence of CPSP/NP in the EP versus the PNB groups, which may reflect clinical relevance, despite the lack of statistical significance.The increased focus on approaches to prevent and treat post‐surgical NP, even more important than the focus on nociceptive pain, is justified by concerns that although NP may be less prevalent than nociceptive pain in pediatric oncology, its treatment is more difficult and requires a longer follow up and complex pharmacological and nonpharmacological management.Although the role of EP in postoperative pain relief is well established, effectiveness of PLP prevention is inconsistently reported.In adults undergoing lower extremity LA, preemptive use of continuous PNB lowered the postoperative incidence of pulmonary complications, acute postoperative pain scores, and opioid use when compared to general anesthesia.Direct comparisons between EP and PNB techniques are limited. Both provide adequate postoperative pain relief and opioid‐sparing effects. Reviews by Von Plato et al. and Ahuja et al. summarized current evidence on RA techniques after major LA.Literature lacks conclusions about whether RA could decrease the incidence of CPSP in LA.Overall, the current literature comparing RA modalities is limited to specific types of surgery for adults. It is important to note the paucity of data in pediatric patients: although RA in children is safe and effective for postoperative pain, little is known about its role in long‐term pain outcomes.When characterizing the NP‐targeted medications dosing, we found that a higher percentage of patients received gabapentin, pregabalin, amitriptyline, and methadone in the EP than the PNB group, and greater dosages were used. Our approach to NP treatment is based on a clinical algorithm, including anticonvulsants , tricyclic antidepressants , and methadone added in a stepwise manner. One in three patients can be expected to require an escalation of the regimen, with addition of amitriptyline and/or methadone to gabapentinoids.To establish preemptive analgesia, in our practice, gabapentin is started 3–5 days prior to surgery, as 15 mg/kg/day divided into three doses. Preoperative gabapentin may be effective to reduce the incidence of CPSP.Amitriptyline doses in our study as mean (SD) (mg/kg/day) were an initial and maximum of 0.472 (0.211) and 0.820 (0.369), respectively, and are among the higher values reported in literature, which start with 0.1 mg/kg and gradually increase to a maximum of 1 mg/kg at bedtime.d‐aspartate receptor antagonist, which mediates the effectiveness for NP. There is no maximum dose; instead it can be titrated up  until pain relief is achieved or side effects appear.Our reported mean (SD) initial and maximum methadone dosing (mg/kg/day) of 0.214 (0.0951) and 0.362 (0.209), respectively, are consistent with previously reported dosing.4.1This study has some limitations. Although literature reflects the impact of psychosocial determinants on CPSP development more than biological determinants,5The incidence of CPSP/NP in our population was 23.8% after LS and LA/disarticulation surgeries. LS surgeries with EP treatment had a significantly lower duration of pain compared to the other combinations of surgery and RA. The median duration of CPSP/NP of 38 days for EP versus 50 days for PNBs may have clinical significance, suggesting that EP interventions provide better prognosis of pain relief over time. Our study provides a comprehensive analysis of NP‐directed medication dosing regimens in CPSP/NP treatment, indicating higher dosing regimens than previously reported and providing a platform for development of standardized regimens. Prospective multi‐institutional studies are necessary to further elucidate the association of RA on CPSP in pediatric oncology and establish refined analgesic treatment regimens.Doralina L. Anghelescu: Conceptualization (lead); data curation (supporting); formal analysis (supporting); funding acquisition (supporting); investigation (lead); methodology (lead); project administration (supporting); resources (supporting); software (supporting); supervision (lead); validation (supporting); visualization ; writing – original draft ; writing – review and editing . Emma Johns: Conceptualization (supporting); data curation (lead); formal analysis (supporting); funding acquisition (supporting); investigation (supporting); methodology (supporting); project administration (supporting); resources (supporting); software (supporting); supervision (supporting); validation (supporting); visualization (supporting); writing – original draft ; writing – review and editing . Shalini Bhatia: Conceptualization (supporting); data curation (supporting); formal analysis (lead); funding acquisition (supporting); investigation (supporting); methodology (supporting); project administration (supporting); resources (supporting); software (lead); supervision (supporting); validation (supporting); visualization (supporting); writing – original draft (supporting); writing – review and editing (supporting). Michael J. Frett: Conceptualization (supporting); data curation (supporting); formal analysis (supporting); funding acquisition (supporting); investigation (supporting); methodology (supporting); project administration (supporting); resources (supporting); software (supporting); supervision (supporting); validation (supporting); visualization (supporting); writing – original draft (supporting); writing – review and editing (supporting). Zhaohua Lu: Conceptualization (supporting); data curation (supporting); formal analysis (supporting); funding acquisition (supporting); investigation (supporting); methodology (supporting); project administration (supporting); resources (supporting); software (supporting); supervision (supporting); validation (supporting); visualization (supporting); writing – original draft (supporting); writing – review and editing (supporting).The authors have stated explicitly that there are no conflicts of interest in connection with this article.This study has been approved by the appropriate institutional review boards and has abided by ethical standards regarding studies involving human participants. All persons gave their informed consent for the use of patient data prior to inclusion in this study.The content is solely the responsibility of the authors and does not necessarily represent the official views of the National Institutes of Health.


Introduction: The neuromodulating effects of transcutaneous-spinal Direct Current Stimulation (tsDCS) have been reported to block pain signaling. For patients with chronic pain, tsDCS could be a potential treatment option. To approach this, we studied the effect of anodal tsDCS on patients with neuropathic pain approaching an optimal paradigm including the investigation of different outcome predictors. Methods: In this randomized, double-blinded, sham-controlled crossover study we recruited twenty patients with neurophysiologically evaluated neuropathic pain due to polyneuropathy (PNP). Variables  were reported daily, one week prior to, and one week after the stimulation/sham period. Anodal tsDCS  was given once daily for three days during one week. BDNF-polymorphism, pharmacological treatment, and body mass index (BMI) of all the patients were investigated. Results: Comparing the effects of sham and real stimulation at the group level, there was a tendency towards reduced pain, but no significant effects were found. However, for sleep quality a significant improvement was seen. At the individual level, 30 and 35% of the subjects had a clinically significant improvement of pain level and sleep quality, respectively, the first day after the stimulation. Both effects were reduced over the coming week and these changes were negatively correlated. The BDNF polymorphism Val66Met was carried by 35% of the patients and this group was found to have a lower general level of pain but there was no significant difference in the tsDCS response effect. Neither pharmacologic treatment or BMI influenced the treatment effect. Conclusions: Short-term and sparse anodal thoracic tsDCS reduces pain and improves sleep with large inter-individual differences. Roughly 30% will benefit in a clinically meaningful way. The BDNF genotype seems to influence the level of pain that PNP produces. Individualized and intensified tsDCS may be a treatment option for neuropathic pain due to PNP. Neuropathic pain is widely considered to be one of the most challenging pain conditions to treat . AlthougPolyneuropathy (PNP) is a progressive condition where multiple peripheral sensory and/or motor nerves are affected, resulting in varying degrees of muscle weakness, sensory impairments, and often neuropathic pain . PatientGenerally, pharmacological treatment for neuropathic pain at best only offers partial pain relief and often has unmanageable side effects. Thus, today’s treatment outcomes are often inadequate and unsatisfactory ,2. Neuromodulation is a rapidly growing field in medicine. Conceptually, it includes different stimulation techniques to alter or counteract various imbalances of the central, peripheral, or autonomic nervous systems . With thA major obstacle for neuromodulation techniques is the large interindividual variation regarding stimulation effects ,7,8,9. TIn the present study, we aimed to evaluate the effect of anodal tsDCS on PNP patients with neuropathic pain located in the feet/lower extremities. The protocol that was tested was one that would be reasonable in clinical practice (three visits per week). We genotyped the BDNF and evaluated the effect of pharmacological treatment and body size. In doing so, we sought a possible way to optimize, possibly individualize, the treatment protocol for tsDCS in this group of patients.A total of 21 patients with neuropathic pain affecting lower extremities were recruited for this study. Information regarding weight, height and pharmacological treatments were gathered at the start of the study. All patients were recruited from the neurophysiological clinic in Linköping, Sweden, and had previously performed quantitative sensory testing (QST) between 2019 and 2022. The study was registered in research-web.org.This was a randomized, double-blind, sham-controlled crossover study . All subEvaluations were made using visual analogue scales  one week prior to, and one week after the stimulation/sham period. The subjects were used as their own controls, hence before gathering the baseline values for the second stimulation period, there was a washout period of one week. Patients between ages 18 and 85 with clinically-proven, therapy-resistant, painful polyneuropathy from the feet were eligible for the study. All patients with deviating QST test results from the feet, compatible with small fiber neuropathy  were recThe protocol was approved by the Ethical Review Board and all participants signed forms accepting participation prior to the start of the study.2) was delivered for 20 min, whereas the sham stimulator did so for only 20 s before returning to zero. The current was delivered through two electrodes . Automatic control of resistance would have hindered stimulation at a resistance above 15 mΩ. The electrodes were placed and fixed with adhesive tape with the subject in a prone position. From the edges of the electrodes, the anode was positioned 7.5 cm caudally and cathode 7.5 cm cranially to the spinous process of the 10th thoracic vertebra, i.e., 15 cm between the edges of the electrodes. Stimulations were given on three days  for one week. During the stimulation, the subjects were questioned every 5 min if they had a perception from the electrodes.For anodal stimulation, a constant electrical current of 2.5 mA  for a week before and after each stimulation week. The parameters that were used were level of general, pin pricking, and burning pain  and sleep quality . The mean score for morning/evening was used to represent each day. Calculations for a sham-corrected effect was made for the results ([(baseline 1-sham)-]). Body mass index (BMI) was calculated according to the formula mass (kg)/height2 (m). Pharmacological treatments with potential mechanism on neuropathic pain were noted on each patient. During the analyses, patients were categorized according to their BDNF genotype, BMI, and if they had any pharmacological treatment for neuropathic pain and then compared to their counter group with regards to the stimulation effect. t-test was used to test for differences between the baseline levels before the first and second stimulation periods. A pre-test for carryover effect were made according to the method described by Wellek et al.  for the four evaluated parameters are given in The results regarding sleep quality show that at day 1 35% (7/20) of the patients experienced a sham corrected, clinically significant improvement (≥30% above baseline) with real tsDCS. In parallel to pain sensations, the effect declined over the week after stimulation to 15% (3/20) at day 7. Remarkably, a few patients reported a greater effect from sham stimulation compared to real tsDCS.Non-invasive neuromodulation techniques including tsDCS, have been shown to affect different aspects of central nervous system functioning, both at the cerebral  and at tThe exact mechanism of tsDCS remains to be clarified. However, it is apparent that the effects on the spinal cord are polarity dependent, and anodal stimulation has been shown to inhibit nociceptive responses ,7,8,9. EThe location for stimulation was chosen based on modelling studies demonstrating that the electric field that is created by tsDCS is dependent on the location of the electrodes with field effects on several segments and pathways through the depth and length of the spinal cord . At the This study replicated the findings from numerous previous investigations ,9, i.e.,At the group level, there were no significant differences between the two studied BDNF genotypes . At the individual level, however , we founIndividual phenotype might also be a prognostic factor. Fat tissue has lower electrical conductivity compared to muscle tissue ,25. HencAnother factor to consider is pharmacological treatment. Previous studies have shown that pharmacological interactions affect the stimulation effects of tDCS ,27. TypiThis study does have some limitations. Although individuals with clinically significant improvement were found, we recognize that the small sample size might be a limitation to the conclusions that can come from this study. No sample size calculation was made as this was a first study attempting to evaluate the effect of a structure that might be applicable to clinical routine care. We recruited patients with a broad etiology with regards to their neuropathic pain, which could potentially be a confounding factor to the effect and mechanisms related to tsDCS. Further, different pharmacological treatments for pain were recognized, and the different mechanisms of these medicines could potentially affect the tsDCS effect. Applying a simple arrangement with great potential for home treatment, we show that in patients with polyneuropathy, anodal tsDCS has positive effects on sleep quality and a promising pain reducing effect. The inter-individual variation in response to the stimulation seems to be multifactorial. More studies are needed to optimize the tsDCS protocol for pain treatment and to identify predictor factors. However, after a short trial period, as in this study, responders can already be identified. Therefore, and given its ease of use and lack of serious side effects, trials with more intense protocols employed over longer time in the patient’s home, seem warranted.


Temporomandibular disorders are a major public health problem affecting approximately 10% of the population, currently the second most common musculoskeletal condition after chronic low back pain, and causing disability and pain in patients who suffer from them, limiting the individual’s daily activities and quality of life. Intra-articular injections have been proposed as a specific treatment for joint inflammation and degeneration and have been shown to increase mouth opening and decrease pain associated with these disorders, although long-term follow-up is scarce in the literature. Our study compared the efficacy on TMJ pain of intra-articular injections of betamethasone, sodium hyaluronate and platelet-rich plasma in a sample of 114 patients, with a three-year follow-up, and found that both platelet-rich plasma and sodium hyaluronate led to significant pain-free time after treatment; betamethasone was less effective.Temporomandibular joint disorders are associated with pain and reduced jaw mobility. The aim of this study was to compare the long-term effect on pain of intra-articular TMJ injections of betamethasone, sodium hyaluronate and platelet-rich plasma. The sample was made up of 114 patients, who were randomly distributed into three groups at least three years ago and who achieved a total remission of pain after treatment. We found that the median number of months without pain was, according to each group, as follows: platelet-rich plasma: 33; sodium hyaluronate: 28; betamethasone: 19. Both platelet-rich plasma and sodium hyaluronate lead to significant pain-free time after treatment; when we compare bethametasone with the two other substances, it proved to be very ineffective.  Temporomandibular joint disorder (TMD) is a significant public health disorder affecting between 5% and 12% of the population on average. After persistent low back pain, TMD is the second most prevalent musculoskeletal disorder causing discomfort and impairment. [The most common clinical manifestations are pain, mouth opening limitation, muscle or joint tenderness on palpation, changes of mandibular movements, joint sounds and otologic complaints like tinnitus or vertigo .Temporomandibular joint disorders (TMJDs) is a collective term that refers to a range of pathologies affecting the jaw joints and associated structures, resulting in internal joint space dysregulation, bony changes and degenerative pathologies. TMJDs are characterized by pain, joint noise, limited range of motion, impaired jaw function, deviation when opening and closing the mouth and open locking. They are a very common pathological agent affecting about 10% of the population, and are twice as frequent in women than in men ,5,6.In clinical practice, different treatments have been proposed to alleviate joint pain and disc displacement, including conservative therapies such as non-steroidal anti-inflammatory drugs (NSAIDs), mandibular rest, splints and physiotherapy, as well as surgical procedures such as arthrocentesis, disc repositioning or discectomy in patients who do not respond to conservative treatments. A conservative approach should always be taken primarily ,8.In 1953, Horton et al. were the first to propose intra-articular administration of corticosteroids (CS) for the treatment of temporomandibular joint osteoarthritis (TMJO) ,11.Sodium hyaluronate (SH), a hyaluronic acid (HA) derivative, is a material of high molecular density and high viscosity, essential for joint lubrication and cartilage protection, which would reduce granulation tissue formation and intra-articular adhesions, having been proposed as an additional therapy with similar therapeutic effects ,13. TherPlatelet-rich plasma (PRP) is an autologous blood product obtained by peripheral venipuncture and subsequent centrifugation. The concentrated plasma product contains a high concentration of platelets, which play important roles in tissue homeostasis and control of inflammation, as well as in inhibition of chondrocyte apoptosis, bone and vascular remodeling and collagen synthesis. Certain studies have compared the clinical results of intra-articular injection of PRP with other conservative treatment methods such as corticosteroid injection ,16,17.Platelets are enucleated cells derived from megakaryocytes . When plThe aim of this study was to analyze how long a patient could remain pain free after being treated with one of three intra-articular infiltrations—betamethasone, SH or PRP—as a continuation of a previous study  that assA sample of 114 patients who were diagnosed with TMJ arthralgia was selected, according to the original version of the diagnostic criteria for TPMJDs, such as local pain modified with movement and pain on palpation, and who were treated with intra-articular injection of PRP, SH or betamethasone, achieving no pain after treatment and who were followed up for at least 3 years, in order to study the duration of the treatment effect. The patients were recruited and treated, after the conservative approach showed no effect, in consultations within the framework of the Occlusal Rehabilitation Course of the University of Coimbra, organized by the Faculty of Medicine. All patients agreed to participate in the research and signed the consent forms. This study was conducted in accordance with the Declaration of Helsinki and was approved by the ethics committee of the Faculty of Medicine of the University of Coimbra . This study was approved on 25 June 2017 by the institutional review board (IRB 06-2017-096). No patient has dropped out from the study.Inclusion: All patients with a clinical history of more than 6 months of TMJP that is modified by mandibular movement in function or parafunction; pain present on clinical examination on opening, lateral movements or palpation; and without previous effective treatment. All patients included in this study have achieved, after treatment, a grade 0 according to the Visual Analogic Scale (VAS).Exclusion: patients who had received effective previous treatment for TMJ dysfunction; patients suffering from any rheumatic pathology such as rheumatoid arthritis or psoriatic arthritis (including juvenile arthritis); patients undergoing hypnosis; pregnant or breastfeeding women; patients under 18 years of age; and patients who had partial or no relief of the pain condition and had to receive another treatment. Prior to treatment, patients were randomly assigned to three groups: patients receiving an intra-articular injection of PRP, betamethasone or SH.®, Schering-Plough Labo, Heist-Op-Den-Berg Belgium 14 mg/2 mL) or 1 mL of SH . The exact puncture point was determined by tracing the canthus-tragus line and measuring 10 mm from the tragus and 2 mm below the line. The zygomatic arch was palpated, and patients were asked to open their mouth to move the condyle forward. The position of the needle was from outside to inside, top to bottom, and back to front. Patients were informed that they might experience discomfort in the region. No analgesic or anti-inflammatory drugs were prescribed. During the whole process, all patients were always followed by the same professional. Alternatively, after signing the informed consent, patients were randomly assigned to the corresponding treatment group. Each patient’s treatment was assigned by means of a randomization list automatically generated before the start of the study in which the treatment approach was determined. The following protocol was followed: after disinfection of the preauricular area, patients were injected with 1 mL of articaine (40 mg/mL) and adrenaline (10 μg/mL). A 23-gauge needle was used to inject 1 mL of betamethasone .In the statistical analysis, a significance level of 0.05 was considered, having been performed on the IBMThe sample of this study was composed of 114 individuals, 27 men and 87 women randomly distributed in 3 groups.In the betamethasone group there were 8 men and 26 women, the mean age was 41.2 years, the youngest being 18 years and the oldest 66 years.In the SH group the gender distribution was 9 men and 30 women. With respect to age, the minimum was also 18 years, while the maximum was 65 years.Finally, in the PRP group, composed of 10 men and 31 women, the age range was 18 to 66 years, with a mean of 37.6.The maximum number of months of follow-up of the patients was 36 months (3 years). It is important to mention that 33 of the 41 patients treated with PRP were permanently pain-free. The same result was obtained by 19 of 39 patients treated with SH. The worst result was observed in the betamethasone group, in which only 9 of the 34 patients were able to remain pain-free for the entire 36-month period.The following table shows the statistics of age and sex in the three groups defined by the substance injected .Statistics on pain-free time are presented in p = 0.005) between the groups in terms of administered substances, but neither age (p = 0.827) nor sex (p = 0.403) have an impact on pain-free time. To compare the groups among themselves, the Dunn-Sidak post-hoc test was chosen, whose results were:-p = 0.048PRP vs. SH: -p < 0.001PRP vs. Betamethasone: -p = 0.069SH vs. Betamethasone: Statistically significant differences are observed  or cortico-steroids (betamethasone) into the TMJ have not demonstrated substantial differences between the two therapies. Follow-ups of one or two years reported sustained and substantial reductions in TMJ symptoms and increased joint mobility ,38; TanaPRP has an effect on chondrogenic differentiation and tissue remodeling. It has been studied more in other joints than in the TMJ . Given tA study by Joshi Jubert et al. concluded that PRP was effective in relieving pain and improving TMJ function, although the effects of PRP were comparable with the effects of corticosteroids in patients with advanced stage osteoarthritis (OA) . Other sIn general, the results of the different studies on the use of betamethasone, SH and PRP in the treatment of TMJ diseases coincide with the results of our studies. Our first study  comparedIn our study, both PRP and SH led to significant pain-free time after treatment; betamethasone was less effective. However, more rigorous randomized controlled trials with long-term follow-up are needed.


Background: Neuromuscular conditions, such as cerebral palsy, are the most common motor disabilities in the pediatric population. Children with these conditions frequently have accompanying hip deformities that require pelvic and femur osteotomy to correct the spastic hip dislocations. However, postoperative pain management remains an elusive and challenging problem. The purpose of this study was to determine whether postoperative use of epidural analgesia in patients with neuromuscular conditions provided similar outcomes with regard to pain scores, length of stay, duration of foley placement, duration of pain control, and complications as compared to traditional pain management regimens. To our knowledge, this is the first study comparing the use of epidural analgesia to conventional pain relief modalities following hip reconstruction in patients with neuromuscular conditions.Methods: A retrospective cohort study was performed using records of pediatric patients with neuromuscular conditions treated at our tertiary care center between January 2009 and December 2019. Patients with neuromuscular conditions treated with epidural or non-epidural analgesia for pain relief following unilateral or bilateral proximal femoral osteotomies, pelvic osteotomies, or open hip reduction were eligible for study inclusion. Multiple linear regression was used to determine differences in length of stay, pain score, pain modality, duration of Foley placement, and complications between the two cohorts.Results: Seventy patients met the inclusion criteria for the study. In all, 58 patients underwent unilateral procedures, of which 30 (52%) received epidural analgesia, and 28 (48%) received non-epidural pain control modalities. Demographic and baseline characteristics were similar among the cohort, except for BMI, which varied slightly. Average pain scores and pain control duration were not statistically different between the pain control modalities. After controlling for demographics, procedure, and immobilization type, the epidural group experienced significantly increased length of stay  and duration of Foley placement . Complication rates between the two groups were not statistically significant.Conclusions: The use of epidural analgesia in children with neuromuscular conditions was associated with comparable pain scores, despite the increased length of stay and duration of Foley placement. No statistically significant difference in complication rates was observed between patients receiving epidural anesthesia and those receiving traditional pain modalities. Neuromuscular conditions, such as cerebral palsy (CP), represent a heterogeneous group of permanent motor disorders that appear early in life. Prevalence rates suggest CP occurs at a rate ranging from 1 to 4 per 1000 births making it the most common childhood motor disorder. Although the etiology remains unclear, CP is an upper motor neuron disease that results from insult to the brain during early development .Decreased range of motion, pain, and joint contractures are also characteristic of CP, with one of the most common locations being the hip. Depending on the severity, musculoskeletal manifestations can result in modest impairment or severe disability affecting the patient's posture, gait, and participation in activities . MoreovePost-surgical treatment of pain, in these often cognitively impaired children, also represents a significant challenge. Most of these patients suffer from severe intellectual delay and often have issues with communication and, therefore, cannot self-report their pain -7. SinceEpidural analgesia is often continued for two to three days post surgery, depending on institution protocols . During After obtaining approval from the Children's National Hospital Institutional Review Board (Pro00013336), a retrospective chart review of pediatric hip reconstructive procedures in which either epidural or non-epidural analgesia was administered for postoperative pain relief. We identified patients who underwent unilateral or bilateral proximal femoral osteotomies, pelvic osteotomies, or hip open reductions from 01/01/2009 - 12/02/2019 at Children's National Hospital, which yielded 227 patients. We excluded patients who had a revision surgery and those without neuromuscular conditions. The final cohort consisted of 70 cases that met all criteria, of which 58 underwent unilateral procedures. Demographics, laterality of surgery, postoperative pain control modality, duration of pain control modality, length of stay, and postoperative complications were recorded. Pain scores were recorded using the Face, Legs, Activity, Cry, Consolability (FLACC) pain scale. A low, high, median, and mean pain score was recorded for each patient. Complications were defined as readmission to hospital for a respiratory or orthopaedic issue including but not limited to re-dislocation or loss of surgical fixation. Additionally, we included soft-tissue complications, such as pressure ulcers, or any superficial or deep wound infection.Summary statistics on demographic and baseline patient characteristics were presented as mean with standard deviation for continuous data and frequencies with percentages for categorical data. Continuous and categorical baseline variables were compared between epidural and non-epidural groups using unpaired t-test and Chi-square test or Fisher’s exact test (if expected cell count <5) respectively. Normality assumptions were checked using a statistical test  as well as graphical methods . Only the length of stay variable was found to significantly deviate from normality.Pain scores, duration of Foley placement, and duration of pain control modality between two groups were compared using unpaired t-test followed by multiple linear regression analysis adjusted for potential confounders age, BMI, procedure type, and immobilization type. Length of stay was compared using non-parametric Mann-Whitney U Test. Complication rates including hospital readmission, respiratory difficulties, re-dislocation, loss of surgical fixation, and soft-tissue complications were compared using Chi-square test. All statistical tests were two-sided and performed at the 0.05 level of significance. Statistical analysis was performed using R statistical software, version 4.0.0 .Of the 70 patients in the dataset, 58 patients underwent unilateral procedures, 28 (48%) used non-epidural pain-control modalities, and 30 (52%) used epidural analgesia. Both groups were comparable in terms of the baseline characteristics except for BMI which was slightly higher in the non-epidural group Table .Pain scores , length of stay, duration of Foley placement, duration of pain control modality, and complications were compared between the two groups. Average pain scores were similar between the two groups. Duration of Foley placement was significantly higher in the epidural group compared to the non-epidural group (P=0.008). Although complications were higher in the epidural group, it was not statistically significant  , but there were no significant differences in any of the other pain score parameters. These results demonstrate that the pain control is comparable between epidural and non-epidural analgesia, but that epidural analgesia has the additional drawbacks of increasing length of stay and duration of Foley placement in this patient population. It is important to note, while the difference in lowest pain score values between the groups was statistically significant, no significant conclusions can be drawn from this particular parameter, as the other pain score parameters were not statistically significant.Patients receiving epidural analgesia maintained their Foley catheter for an average of 1.04 more days than the non-epidural patients, which could pose a greater risk of complications related to catheterization such as urinary tract infection . HoweverAlthough the difference in the number of complications between the two groups was not statistically significant, the increased number of complications in the epidural cohort is important to note. More specifically, placement of an epidural catheter has been shown to potentially further increase the risk of adverse complications, including epidural abscess, epidural hematoma, and post-dural puncture headache . At the Prior studies have compared epidural and non-epidural PCA pain control modalities, but the literature is inconclusive on whether epidural analgesia offers any additional benefit to postoperative treatment when compared to traditional multimodal pain control regimens. Chauvin et al. demonstrated that epidural administration of alfentanil resulted in a 39% decrease in opioid consumption as compared to the non-epidural PCA modality, but ultimately, the oxyhemoglobin desaturation between the two groups was comparable -11.Other studies suggest no significant differences in the incidence of drug-related complications, such as over-sedation, oxygen desaturation, and respiratory depression between epidural and PCA groups, and describe a modest improvement in analgesia . HoweverThis study does have several limitations. Primarily, it was retrospective nature, there was a lack of randomization among our sample, which may pose a selection bias. The selection bias is inherent in a retrospective review like this, as an epidural may have been placed in children who were having more extensive surgery or bilateral operation. This could also be an alternative explanation for why there were longer stays in the epidural group. Additionally, although baseline demographic characteristics were not significantly different, our sample had a wide spectrum of BMI recordings which poses a challenge in ruling out possible comorbidities influencing our findings. Furthermore, pain scores obtained from our patient sample are limited by the difficulty of attaining pain scores from children with neuromuscular conditions, such as cerebral palsy, given their inability to reliably self-report pain location and intensity.Studies suggest that children with CP already experience twice as many complications and have high reoperation rates following hip surgery compared to their non-CP counterparts -23. TherUse of epidural analgesia in children with neuromuscular conditions was associated with comparable pain scores, despite the increased length of stay and increased duration of Foley placement. No statistically significant difference in complication rates was observed between patients receiving epidural anesthesia and those receiving traditional pain modalities. Given the paucity of data surrounding the use of epidural anesthesia in children with neuromuscular conditions, future research should seek to further investigate the efficacy of epidural analgesia for postoperative pain management in children with neuromuscular conditions.