IntroductionOsteoarthritis is one of the most common disorders of the temporomandibular joint (TMJ). The complex etiopathogenesis of the temporomandibular disorders (TMDs), and the variability of symptoms make it difficult to adopt standardized therapeutic protocols. Recently, platelet-rich plasma (PRP) injections have been applied into the TMJ in patients with TMJ osteoarthritis. On the other hand, arthrocentesis has received a widespread acceptance, as a minimally-invasive surgical procedure for TMDs. This study aimed to assess and compare the effect of each of these protocols  in the management of TMJ osteoarthritis.MethodsA single-blinded randomized clinical trial was conducted on a sample of 33 participants with limited mouth opening, pain on function and joint sounds due to TMJ osteoarthritis. Participants were assigned randomly into three groups: Arthrocentesis with PRP group; PRP group; Arthrocentesis group. Maximum mouth opening (MMO), pain and joint sounds were re-evaluated during a six-month observation period. Intra- and inter-group comparisons regarding these variables were performed.ResultsParticipants in all study groups showed statistically significant improvement in terms of MMO and pain during the six-month postoperative period (p<0.05), and showed no significant improvements regarding joint sounds (p>0.05). Pain evaluations showed better outcomes in arthrocentesis with PRP group in comparison to arthrocentesis or injectable PRP alone after six months of follow-up (p<0.05). There were no significant differences in the outcomes of MMO and joint sounds evaluations between the three groups after six months.ConclusionsWithin the limitations of this study, it can be concluded that the three assessed treatment protocols were effective in improving limited mouth opening and pain in patients with TMJ osteoarthritis. A combination of TMJ arthrocentesis and PRP intra-articular injections showed the best outcomes regarding pain symptoms. None of the tested treatment protocols showed improvement in terms of articular sounds. Temporomandibular joint (TMJ) is one of the most complex joints in the human body from the anatomical and physiological perspectives. TMJ is the only bilateral joint, where the right and left joints are fused and function together during mandibular movements. Moreover, TMJs comprise compound ginglymoarthrodial articulation between the mandibular condyles, articular discs, and glenoid fossae of the temporal bones . TMJ is A wide term has been evolved covering vast TMJ-related conditions, temporomandibular disorders (TMDs) . TMDs weThe treatment for TMJ-OA mainly includes non-surgical and minimal-invasive options, e.g., physical therapies, dietary adjustments, occlusal splints, oral non-steroidal anti-inflammatory drugs (NSAIDs), muscle relaxants, intra-articular drug therapies, and arthrocentesis , 8. ArthPlatelet-rich plasma (PRP) is a biological therapy that comprises an autologous concentrate of platelets acquired by blood centrifugation . This coStudy design and settingA total of 33 participants were enrolled in this single-blinded randomized clinical study. Patients who developed a unilateral TMJ-OA were selected from cases admitted to the Department of Oral and Maxillofacial Surgery  in the period between April 2020 and September 2021. The study protocol was approved by the Research Ethics Committee of Damascus University (registration no. 2019-2504).Sample sizePriori power analysis was performed using G*Power software version 3.1.9  for estimating the sample size for the current study. The total sample size required to detect a meaningful effect with a desired power of 95% was 27 participants. After considering a potential drop-out rate of 15%, the sample size was determined to be 33 participants (11 participants for each group).Participants recruitmentAll participants provided their consent prior to any intervention regarding this trial. Inclusion criteria included TMJ-OA patients aged more than 18 years, class I molar and canine relationship, baseline mouth opening less than 40 mm, unilateral TMJ pain with ipsilateral joint sounds, limited lateral mandibular movement (<8mm) in at least one direction, and poor masticatory efficacy. Poor masticatory efficacy was defined as participant’s inability to eat all kinds of solid food. Reported pain on palpation, pain on function, limited mouth opening, joint crepitation during function, and soft end feeling were the main clinical findings used to diagnose TMJ-OA in the present study. Exclusion criteria were rheumatoid diseases, history of TMJ surgery, articular adhesion, TMJ ankylosis, tumors of the condyle, history of condylar fracture, pregnancy, growth disorders, and bilateral joint pain and/or sounds. Participants with ipsilateral impacted, partially erupted, or buccoverted maxillary third molars were also excluded. Extraction of maxillary third molar, if indicated, should be done at least one month before recruitment. Also, patients who reported improvement of symptoms after other non-surgical treatments  were not included in this study. Every participant had a thorough clinical examination to confirm the diagnosis of TMJ-OA, which included lateral palpation of the TMJ area with index fingers just anterior to the tragus. A standard palpation pressure of about 500g was implemented during TMJ palpation. Palpation was done by a surgeon who had received prior training on a scale to expertise in applying the standard digital palpation pressure during TMJ examination.Randomization and allocation concealmentParticipants were randomly assigned into three groups. Differences between study groups were based on the interventional treatment protocol to be implemented. Participants were either assigned to arthrocentesis with PRP treatment group, PRP only group, or arthrocentesis only group. Randomization was performed with aid of computer-generated random sequence. The allocation sequence was concealed in opaque, sequentially-numbered, sealed envelopes with a total of 33 envelopes. This was done by a third-party person who was not involved in the research project. Dark paper inside each envelope was used to deprive its permeability to light. Participants’ details (name and age) were written on the sealed envelopes that were opened only when it was time to allocate to treatment protocol after all baseline assessments were completed.Baseline and outcome measuresAll study participants had unilateral TMJ pain, ipsilateral joint sounds, and limited mouth opening at baseline. Baseline measurements of pain and maximum mouth opening (MMO) were done preoperatively. Pain was assessed by asking study participants to indicate the pain level on a 10-cm visual analog scale (VAS), where score 0 indicated “no pain at all”, and score 10 indicated “the worst pain ever”. Baseline MMO was measured as the distance in millimeters between the incisal edges of upper and lower incisors during maximal opening. Vernier caliper was used to measure MMO. Outcome measures were joint sounds (present/absent), MMO, and pain. Re-assessment of these variables was done in two follow-up timepoints.InterventionsTMJ arthrocentesis procedures and related surface landmarks were in line with Lin et al. . ProceduPovidone-iodine 10% was used for skin disinfection preoperatively. Local anesthetic solution  administration was done, and auriculotemporal nerve block was performed from Point F. A 27-gauge needle was inserted into point F and advanced until touching the posterior border of condylar neck. Negative aspiration before auriculotemporal nerve block was confirmed to avoid injecting into a blood vessel. For each participant in all study groups, 21-gauge cannulas were inserted into each of D and E points in superior, anterior, and inward directions to a depth of about 20mm while his/her mouth was open. Normal saline (1 ml) was injected through point D, while observing point E cannula to drain and ensure that the cannulas tips reached their target. Arthrocentesis of the TMJ was performed by injecting 50ml of saline solution over about 20min via point-D cannula allowing the elimination of synovial fluid and potential inflammatory mediators via the cannula at point E. In the PRP group, arthrocentesis was not performed. Instead, the point-E cannula was removed, and PRP was injected through the cannula at point D. Injectable PRP was prepared from venous blood (6ml), mixed with 3.2% sodium citrate as an anticoagulant, and centrifuged at 1000 rpm for 10 minutes. Intra-articular PRP injection (1ml) was performed in the PRP group and just after arthrocentesis in the “arthrocentesis with the PRP” group. In the arthrocentesis group, no intra-articular PRP prolotherapy was performed.Follow-upPatients were kept on a soft diet for one week. Paracetamol 500mg was prescribed thrice a day for five days. Patients' recall appointments were scheduled at one-month and six-month follow-up timepoints to re-evaluate pain, MMO, and joint sounds.Statistical analysisData were collected, and SPSS version 19  was used for statistical analysis. Regarding pain and MMO comparisons, one-way ANOVA was used for intergroup comparisons, and paired Student’s t-test for intragroup comparisons. For joint sounds, Chi-Square tests and McNemar tests were performed for intergroup and intragroup comparisons, respectively. Statistical significance was set at P<0.05.Out of 57 potential participants who were initially evaluated, 33 participants (n=33) with unilateral TMJ-OA were allocated to study groups, and included in all phases of this trial Figure . During All study participants exhibited TMJ sounds, pain on function, and limited mouth opening (MMO less than 40m) at baseline. Intra-group comparisons showed significant differences in mean values between baseline preoperative measurements and after six months regarding VAS pain scores in all study groups . A similar trend was found regarding MMO in the three groups . No significant differences existed between preoperative and six-month postoperative assessments of joint sounds in all study groups (P>0.05). Intragroup differences analysis is shown in Table Mean MMO value in arthrocentesis with PRP group one month postoperatively was 48.82 ±4.19) mm, compared to 44.18 (±4.81) mm and 42.27 (±4.15) mm in PRP-only and arthrocentesis-only groups respectively. This intergroup difference was statistically significant (P=0.005). However, there were no significant differences between the three groups in regard to MMO in the six-month follow-up timepoint (P=0.090). In contrast, mean VAS pain scores showed no significant differences between the study groups one month after the interventions (P=0.182). But, in the six-month follow-up timepoint, these differences in mean pain score between arthrocentesis with PRP group (0.73±0.79), PRP-only group (2.18±1.25), and arthrocentesis-only group (2.82±1.25) were significant (P<0.001). Intergroup differences are presented in Table 9 mm, comHarmsAll procedures were carried out without complications, except for one case where transient partial facial palsy occurred after anesthetic administration and infiltrated to a facial nerve branch.Disorders related to TMJ have always been a thorny issue in the medical field. Symptoms of TMDs negatively affect patients’ quality of life to a great extent . There iThe following clinical variables were assessed at different timepoints: MMO, pain on function and joint sounds. It was found that MMO was improved in all study groups with no significant differences between the groups. Pain scores significantly decreased in all study groups in the short-term one-month follow-up with no intergroup differences. However, pain relief seemed to last longer in arthrocentesis with PRP treatment protocol group. The six-month follow-up showed significant intergroup differences in terms of pain indicating the advantage of the combination protocol over the other treatment protocols. This might be justified as a result of the synergy between TMJ arthrocentesis, which removed debris and inflammatory cytokines within the synovial fluid, reduced articular surface friction, and adjusted the hydraulic pressure within the articular cavity, with the PRP advantages that could aid in the healing process, analgesia, and elimination of inflammatory mediators, and could provide scaffold effect for stem cells migration -18. PainOnly participants in the arthrocentesis-PRP group reported a significant reduction in terms of joint sounds one month postoperatively. Nevertheless, recurrence was observed sooner than expected with no significant joint sounds’ improvement at the six-month follow-up timepoint in comparison to the pretreatment status in all study groups. This might be explained by the potential presence of various influential psychological, social, economic and/or general health factors. This was in line with Moon et al. who found no significant improvement in joint sounds after PRP prolotherapy . DerwichHowever, this study had some limitations. The lack of a definitive assessment of the psychological state of study participants was one of the limitations. Although this was not applicable, taking into account the psychological state of the patients would make the outcomes more credible in representing the changes that occur during the trial. Also, a longer observation period for outcomes of treatment protocols would add a greater value in presenting and comparing the long-term effect of each TMJ-OA treatment protocol. Moreover, it was almost impossible to find TMJ-OA patients without parafunctional habits, e.g., bruxism. Therefore, bruxism and other parafunctional behaviors could not be excluded from the current study. Further, postoperative paracetamol and soft diet could have constituted as potential sources for bias. However, pain assessment was not performed in the first days when patients were on soft diet and allowed to take only paracetamol painkiller to control postoperative pain. Paracetamol was sufficient for pain control in all the patients, as the study interventional procedures were minimally invasive. Soft diet and painkillers were certainly not the causes of symptoms improvement because, as research methodology indicated, all participants were diagnosed with unilateral TMJ-OA that had failed to resolve by other non-invasive treatments including painkillers and dietary modifications prior to enrollment in the present study.This study confirmed that TMJ arthrocentesis was a safe procedure with very limited complications. Out of the 22 cases that underwent arthrocentesis with or without PRP prolotherapy in this trial, only one case presented transient neurological complication related to the auriculotemporal nerve anesthesia. Complications that could develop during and after TMJ arthrocentesis were considered to be minimal and temporary [Within the limitations of the current study, it can be concluded that it was beneficial to use arthrocentesis and/or PRP injection in the management of osteoarthritis symptoms. Arthrocentesis alone, PRP alone, and a combination protocol provided improved results in terms of the limited mouth opening and pain. Pain relief seemed to be better in the arthrocentesis-PRP treatment protocol. However, these protocols seemed to have no positive effect in the management of joint sounds in TMJ-OA.


Degenerative disc disease is a common cause of chronic low back pain. Surgical intervention is an invasive treatment associated with high costs. There is growing interest in regenerative medicine as a less invasive but direct disc treatment for chronic discogenic low back pain. Study Design. Prospective cohort study. Setting. Single, multiphysician center. Patients. 32 adult patients undergoing intradiscal injection of autologous BMAC for the treatment of primary discogenic low back pain. Interventions. Intradiscal injection of autologous BMAC. Main Outcome Measures. Primary outcome measure is visual analog back pain scale (VAS back pain). Secondary outcome measures include ODI, VAS leg pain, and EQ-5D-5L scores. Outcomes were compared from baseline to 1 year.  To evaluate clinical improvement of primary discogenic low back pain with intradiscal injection of autologous bone marrow aspirate concentrate (BMAC). p < 0.001) and 2.8 to 1.3 (p = 0.005), respectively. Mean ODI scores decreased from 33.5 to 21.1 (p < 0.001), and EQ-5D-5L scores improved from 0.69 to 0.78 (p = 0.001). Using established MCID values, 59.4% had clinically significant improvement in VAS back pain, 43.8% in VAS leg pain, and 56.3% in ODI scores.  Thirty-two patients  with a mean age of 45.9 years were enrolled, giving 92 treated levels. Mean VAS back and leg pain scores improved from 5.4 to 3.0 ( Intradiscal injection of autologous BMAC significantly improved low back pain, disability, and quality of life at one year. This study suggests that intradiscal BMAC has the potential to be an effective nonsurgical treatment for chronic discogenic low back pain. Chronic low back pain is one of the leading causes of disability in both the United States and worldwide, resulting in healthcare expenditures in the tens of billions of dollars –3. DegenRegenerative medicine utilizes the body's cells to promote healing in an area of damage. Bone marrow aspirate concentrate (BMAC) has been shown to contain significant quantities of mesenchymal stem cells (MSC) and growth factors , 11. As All literature searches were conducted using PubMed.This is an IRB approved prospective cohort study conducted at a multiphysician spine practice. Adult patients (>18 years) diagnosed with primary discogenic low back pain, undergoing intradiscal injection of autologous BMAC from 2017 to 2019, and with PROMs completed at 1 year were eligible for inclusion. Patients were excluded if they (1) had an active infection, (2) were on chemotherapy, (3) were diagnosed with a myeloproliferative disorder, (4) were actively using nicotine, (5) were pregnant, and (6) did not complete PROMs. All patients signed informed consent and a Notice of Privacy Practices prior to the procedure.Discogenic low back pain was diagnosed clinically through history, physical examination, and imaging, then confirmed diagnostically using lumbar discography. The subjective and objective clinical evaluation, discogram, and BMAC procedure were performed by the same physician per patient. In the rare case when lumbar discography was not available, pain provocation during disc pressurization at the start of the BMAC procedure was utilized as a surrogate confirmation of pain generators.Subjectively, patients described low back pain with prolonged positioning made worse with bending, lifting, and/or sitting. Those with lower extremity complaints described these as minor compared to the predominant symptom of low back pain. For the objective evaluation, neurologic examination was normal or stable over the preceding 6 months of conservative treatments. All patients received standing lumbar anteroposterior, lateral, flexion, and extension X-rays and a lumbar MRI as part of their workup prior to the BMAC procedure. Findings such as overt instability, acute fractures, or major deformity were ruled out on X-ray. The Modic changes and Pfirrmann grading were obtained from the lumbar MRI, and findings such as severe stenosis, infection, and tumor were ruled out.During lumbar discography, disc pain provocation was identified during disc pressurization with contrast dye injection per disc level, volumetric analysis was also measured with each injection, and dye patterns were assessed using live fluoroscopy during each injection. Subsequently, the patient's reported pain levels prior to and during the discogram, the quality of pain (concordant or nonconcordant), the quantity of dye in milliliters that the disc accepted, and the dye patterns were recorded for each injection per disc level. In this study, concordant pain was defined as the reproduction of the usual low back pain at baseline.All patients underwent a minimum of 6 months of conservative treatment prior to consideration of BMAC injection. This included combinations of activity modification, exercise, physical therapy, chiropractic therapy, acupuncture, steroid injections, and medications . All BMAC procedures were performed in an outpatient facility.Under conscious sedation with intravenous Versed and fentanyl, subcutaneous injection of local anesthetic preceded bone marrow aspiration from each patient's posterior iliac crest utilizing fluoroscopic guidance while following standard sterile technique. Ten milliliter draws using a Jamshidi needle with repositioning between each draw were performed per the technique suggested by Hernigou et al. for a total of either 60 mL or 120 mL depending on the number of levels being treated . Each syIn accordance with the institution's postprocedure protocol, all patients were instructed to avoid high impact activities for 2 weeks, begin physical therapy approximately 2 weeks after the procedure, and avoid NSAID use for 6 weeks. Acetaminophen was recommended to use as needed for pain after the procedure, unless otherwise contraindicated. A prescription for an opioid pain reliever was provided based on individual patient needs.Basic demographics were obtained from electronic medical records and data capture systems. Questionnaires including Visual Analog Scale (VAS) for back and leg pain, Oswestry Disability Index (ODI), and EQ-5D-5L were administered at baseline and 1-year postprocedure to determine outcomes for back pain, leg pain, disability, and quality of life, respectively. Quantities of aspirated bone marrow and injected BMAC were individually measured and recorded during the procedure. Preprocedural MRIs were accessed through the institution's picture archiving and communication system (PACS) and reviewed by 2 fellowship trained spine surgeons. Each affected level was evaluated for Modic changes and assigned an original Pfirrmann grade , 18. Post-tests; the level of significance was set at p < 0.05.Statistical analyses were performed using IBM SPSS V 27.0 . Continuous variables are presented as means and standard deviations and categorical variables as counts and percentages. Comparison of PROM scores from baseline to 12 months was performed using paired Thirty-two patients , having a mean age of 45.9 ± 12.3 years, mean BMI of 27.1 ± 4.2 kg/m ..p < 0.00There were no complications reported relating to the injection within one-year follow-up. Three patients (9.4%) went on to have fusion surgery at levels previously treated with BMAC due to persistent pain at an average of 164.5 days post injection .The results of this study show significant improvements in VAS back pain, VAS leg pain, ODI, and EQ-5D-5L at one-year follow-up when compared to baseline values for patients treated with intradiscal injection of autologous BMAC for discogenic low back pain. Clinically, significant improvements exceeding established MCID values in VAS back pain (59.4%), VAS leg pain (43.8%), and ODI (56.3%) were found . DespiteThe improvement in VAS leg scores was unexpected but has been reported once previously in the literature . While aEarly systematic and comprehensive reviews found that there are limited studies describing validated patient reported outcome measures following intradiscal BMAC injection and the overall quality of evidence was low , 23. HowWhile early research suggested that intradiscal BMAC injection does not improve low back pain, subsequent studies have shown promising results , 25, 26.The most compelling prospective data using standardized outcome measures on this topic are a series of papers published by Pettine et al. on a cohort of 26 patients. These papers were published with follow-up periods of 1, 2, 3, and 5 years –31. In tIn another prospective study, Elabd et al. evaluated patient reported outcomes using a percentage of overall improvement  4-6 years following autologous intradiscal hypoxic cultured BMAC injection in five patients. They found that improvement ranged from 10 to 90%, with a mean improvement of 55%. All 5 patients reported that strength was improved, and 4 out of 5 patients reported that mobility was also improved .p < 0.001) as opposed to the control group which did not exhibit statistically significant improvement in this category. Furthermore, the quantified Pfirrmann grading showed a small but statistically significant improvement in the treated patients while the opposite was found in the control group on MRI at 1 year [In an RCT, Noriega et al. evaluated 24 patients who were randomized into two groups, with the test group receiving allogeneic BMAC and the control group receiving a placebo infiltration of the paravertebral musculature with anesthetic. Of note, this study utilized allogeneic BMAC unlike our study which utilized autologous BMAC. Patient-reported outcomes were collected using the VAS pain scale, ODI, and SF-12 life quality questionnaires coupled with MRI exploration throughout the course of 6 follow-up visits over 12 months. Patients in the treatment arm displayed a significant improvement of 28% with their VAS scores . At the 52-week follow-up, Murray et al.'s intradiscal PRP releasate group had clinically significant improvements in their VAS and ODI scores from baseline . On MRI analysis at 52 weeks, there was no change in the Pfirrmann or modified Pfirrmann grading scores compared to baseline, similar to the findings of this study .Intradiscal BMAC injection is less invasive than surgery; however, surgery can be used as the next treatment option if BMAC injection fails to adequately improve symptoms. There is limited data reported on the number of patients who elect to undergo surgery following an intradiscal BMAC injection. Within the 1-year follow-up period of this study, 3 (9.4%) patients elected to undergo fusion surgery due to continued pain at their affected levels. In the similar study by Pettine et al., 2 (7.7%) patients elected to have a surgical procedure by the 1-year follow-up .The American Academy of Orthopaedic Surgeons published reporting standards for studies relating to platelet-rich plasma and mesenchymal stem cells due to prior inconsistencies in result reporting to help guide future therapy. This study meets 88% of AAOS reporting standards and is a compelling addition to the current literature .Limitations of this study include small sample size and limited follow-up period. While we were able to report statistical improvements in PROMs, long-term changes in these scores beyond one year are unknown. Additional studies with longer follow-up periods and larger sample sizes are needed. Further prospective randomized studies with comparison cohorts are warranted to further evaluate the efficacy of BMAC. The results of this study can serve as a precursor to larger trials. The authors intend to investigate this topic further with larger sample sizes, longer duration of follow-up, and in-depth subanalyses to better account for potential confounders.We did not inject a standardized amount of BMAC per level. The quantity injected was based on the volume accepted per disc and ranged from 1 to 6 mL per level. As such, we cannot draw any conclusions regarding any effects between quantity injected and effect on pain. The BMAC was not cultured or analyzed; no conclusions can be made about the relative stem cell concentrations of each patient's BMAC. Future studies that standardize this portion of the methodology could reduce any possible sources of error in the clinical procedure and further elucidate the relationship between microbiological characteristics of aspirate and clinical outcome.This study suggests that autologous intradiscal BMAC injection has the potential to clinically improve discogenic low back pain at one year while reducing disability ratings and increasing quality of life scores. This regenerative medicine procedure offers a direct and promising adjunct to traditional nonoperative treatments for chronic discogenic low back pain.


Acute postoperative pain is a common complication of inguinal hernia repair. Pain management using local application of anesthetic agents over the skin surrounding the surgical incision may reduce the requirement for other pain medications. Targeted topical analgesics such as 5% lidocaine patches have been known to improve acute and chronic pain. However, the clinical effect of lidocaine patches on postoperative pain after inguinal hernia repair has not been studied, especially in patients undergoing surgery at day surgery units.This is a single-center, prospective, double-blind, randomized, controlled clinical trial. Participants with unilateral inguinal hernia will be randomized to the lidocaine patch group or the placebo patch group. Based on the randomized allocation sequence, either lidocaine patches or placebo patches will be attached near each participant’s surgical wound after open hernia repair under general anesthesia. Participants will be asked to follow up at our outpatient clinic on the first postoperative day and at 1 week after surgery. The primary outcome is pain intensity, which will be measured using the visual analog scale (VAS) at the time of discharge from the day surgery unit. The secondary outcomes are VAS score at 24 h and 1 week after surgery. We will collect and analyze the participants’ clinical data  and demographic characteristics .This trial may not only provide evidence on the efficacy of a 5% lidocaine patch for acute postoperative pain management after unilateral inguinal hernia repair, but also demonstrate the efficacy and safety of the patch for post-discharge pain management.ClinicalTrials.gov NCT04754451. Registered on February 10, 2021.The online version contains supplementary material available at 10.1186/s13063-022-06700-3. Inguinal hernia repair is a commonly performed in general surgery. Acute postoperative pain, which can be moderate to severe in intensity, commonly occurs after open inguinal hernia repair , 2. The Acute postoperative pain is primarily managed with intravenous or oral administration of narcotic or non-narcotic analgesics. However, most of these drugs are systemically administered, which may result in complications such as nausea, vomiting, inhibition of bowel motility, and abdominal discomfort. These adverse effects can occur even after discharge from the hospital, especially in patients undergoing day surgery for inguinal hernia repair.On the other hand, pain management with topical applied analgesics near the surgical incision site may reduce the incidence of complications and drug interactions . A lidocSeveral studies have demonstrated the positive effects of lidocaine patches on acute postoperative pain , 10. HowThis is a single-center, prospective, superiority, double-blind, randomized, controlled clinical trial. This study has been approved by the Institutional Review Board (B-2007-625-006) of Seoul National University Bundang Hospital. Written informed consent to participate will be obtained by the principal investigator at the time of screening for eligibility on the patient’s initial visit to outpatient clinic. After surgery, the experimental group will receive 5% lidocaine patches , and the control group will receive placebo patches that were specially made for this study. The comparator is a well-made placebo patch to evaluate not only the efficacy but also the safety of the 5% lidocaine patch. The overview of the study design is shown in Fig. Evaluating the efficacy of a 5% lidocaine patch on acute postoperative pain in a patient undergoing unilateral inguinal hernia repair at a day surgery unit is the main purpose of this study. This prospective, superiority, double-blind, randomized, controlled clinical trial was designed based on the hypothesis that patients who applied the lidocaine patch will have a lower VAS score at discharge after surgery than patients who applied the placebo patch after unilateral inguinal hernia repair at a day surgery unit.The inclusion criteria are (a) age between 19 and 80 years, (b) American Society of Anesthesiologists risk classification score of I  or II (mild systemic disease), (c) elective open surgery for unilateral inguinal hernia, and (d) admission to and discharge from the day surgery unit on the day of the surgery itself.2), (b) renal insufficiency (serum creatinine level ≥ 1.4 mg/dL), (c) liver insufficiency , (d) known hypersensitivity to amide-based local anesthetics, (e) use of class I antiarrhythmic medication such as tocainide and mexiletine, and (f) refusal to participate.The exclusion criteria are (a) obesity  was determined based on a previous study on patients with ventral hernia that compared the VAS scores of a control group (4.8 ± 1.4) with those of a lidocaine patch group (3.1 ± 1.6) and observed a difference of 1.7 . For a oWe will randomize the participants in a 1:1 ratio to the lidocaine patch group or the placebo patch group. We will achieve block randomization using Random Allocation Software . A research nurse from the anesthesiology department who is not involved in the study will generate the randomized allocation sequence and deliver the allocated patches. The patches will be given directly to the anesthesiologist and surgeon responsible for applying it at the end of the surgery. The participants and researchers (the anesthesiologist and surgeon) who evaluate the patients’ clinical parameters will be blinded to the group allocation.All participants will undergo unilateral inguinal hernia repair under general anesthesia. As pre-treatment, each patient will be injected with 0.03 mg/kg of midazolam on arrival at the operating room. An anesthesiologist will induce and maintain general anesthesia with inhaled anesthetics and opiates using conventional methods. A general surgeon will make a transverse incision of approximately 3 to 4 cm along the skin fold line and perform routine Lichtenstein tension-free mesh inguinal hernia repair. The skin will be closed with subcutaneous interrupted sutures, and skin bond  will be applied. After covering the surgical wound with aseptic dressing, lidocaine or placebo patches will be applied near the surgical wound based on the randomized allocation sequence. Each patient will receive two patches, which will be placed 1 cm above and 1 cm below the surgical wound Fig. .Fig. 2LoBefore discharge from the day surgery unit, we will allow participants to use additional pain medications such as opioids or non-steroidal anti-inflammatory drugs as needed during their recovery from the general anesthesia. Either fentanyl  or ketorolac  will be prescribed. Fentanyl will be prescribed a maximum of three times when a patient experiences pain with a VAS score of > 5. Ketorolac will be prescribed if a patient experiences any adverse effects following fentanyl administration. Oral medications such as tramadol/acetaminophen  will be prescribed to each patient at the time of discharge for pain management. However, additional pain medication or interventions outside of the protocol during the study period, which is from the surgery to 1 week after surgery, are prohibited.This study protocol includes criteria for discontinuing intervention. If a participant withdraws their consent, decides to undergo extra surgery besides the unilateral inguinal hernia repair after random allocation, or if any adverse effects with local anesthetics are shown, they will discontinue the study.The primary outcome is pain intensity measured using the VAS at the time of discharge from the day surgery unit, which is approximately 2 or 3 h after the surgery. We will evaluate each patient’s VAS scores in three situations: at rest, when coughing, and when moving. The secondary outcomes are pain intensity at 24 h and 1 week after surgery. We will evaluate each patient’s VAS score when they visit the clinic for wound dressing on the first postoperative day when the pain-relieving effect of the patch has been worn off. At the follow-up visit 1 week after surgery, we will assess the VAS score, the rates of postoperative complications , and the total amount of oral combination analgesics used after discharge. To understand the correlation with general anesthesia and lidocaine patch, we will additionally analyze the amount of intraoperative opioid use, time to recovery, and pain intensity at 30 min after surgery as a part of the secondary outcomes. The participants’ demographic characteristics, such as age, sex, body weight, and height, will also be recorded.All participants will receive a text message informing them of the date, time, and place for the next outpatient clinic until the end of the study period. In case of no-shows, personal calls to the participant will be made to encourage attendance.U test will be used to analyze the numerical data. For categorical data, we will use the chi-squared test or Fisher’s exact test. All results with a p-value of less than 0.05 will be considered as significant.All statistical analyses will be performed using Statistical Package for the Social Sciences version 25.0 for Windows . The participants’ demographic characteristics will be analyzed using descriptive statistics. After verifying the normality, the Student t-test or Mann–Whitney The principal investigator will report any unexpected problems or non-compliance with the protocol to the participant in question, the Institutional Review Board of Seoul National University Bundang Hospital, the Ministry of Food and Drug Safety, and the reviewing committee, if necessary. If an adverse drug reaction is the cause of death or is life-threatening, the initial report should be submitted within 7 days. If an adverse drug reaction is not fatal, the initial report should be submitted within 15 days. Minor non-compliance cases should be reported every year on a case-by-case basis.Collected information for research will be stored in a locked file in a laboratory, and access to the research file will be restricted to authorized researchers. Unnecessary personal data will be removed, and information such as patient’s name, resident registration number, and medical chart number should not be recorded. The identifying codes linked to personal information will be managed separately. The records of the participants will be kept confidential and will not be moved to other places, and may be sent, if necessary, to an authorized person for supervision of this study.We will disseminate the methods and results of our study to the public through social media, presentations at domestic and international congresses on corresponding areas of interest, and by submitting a paper(s) describing our findings to appropriate scientific journals.Targeted topical analgesics such as 5% lidocaine patches have been known to improve acute and chronic pain , 11. PreThere are a few studies in which a lidocaine patch was used postoperatively for incisions that were longer than a trocar incision. In a randomized controlled trial of 70 patients who underwent radical retropubic prostatectomy with a lower midline incision, a lidocaine patch was applied for 24 h after the surgery, resulting in reduced pain scores and opioid consumption . A similThrough these studies, which included randomized clinical trials and meta-analyses, the safety and efficacy of using a 5% lidocaine patch for acute postoperative pain management has been established. However, most of these studies were on patients who received hospital care and patient-controlled analgesia following surgery, in which the patients’ acute pain was rapidly treated by medical staff. However, the lidocaine patch has advantages comparing with other operative pain managements, such as abdominal muscle fascia and peritoneal nerve block and patient-controlled analgesia. It is non-invasive and simple to apply since the lidocaine patch may produce an analgesic effect without a complete sensory blockage by penetrating skin depth of only 8 to 10 mm . The lidWe have designed this clinical trial to investigate the efficacy of a 5% lidocaine patch for postoperative pain management without additional medical attention. Therefore, we will enroll patients undergoing open unilateral inguinal hernia repair at a day surgery unit. We believe that in addition to demonstrating the efficacy of a 5% lidocaine patch on acute postoperative pain after unilateral inguinal hernia repair, we will be able to provide evidence on its efficacy and safety for post-discharge pain management. In summary, we hypothesize that a 5% lidocaine patch is an effective option for acute postoperative pain management following unilateral inguinal hernia repair, and it can be safely used in an outpatient clinical setting.Clinicaltrials.gov, without any amendments after then. Patient recruitment commenced in March 2021, and the predicted date of completion of this study is October 2021.This protocol version 1.0 was first posted on February 15, 2021, in Additional file 1.


Background: Iliotibial band syndrome (ITBS) is a common leading cause of lateral knee pain. Despite varieties of medical and non-medical treatments proposed for the management of ITBS, the best therapeutic approach for its treatment remained a significant question. The current study aims to compare the outcomes of dry needling (DN) versus shockwave therapy (SWT) in the management of ITBS. Materials and Methods: This randomized clinical trial was conducted on 40 patients diagnosed with ITBS. The patients were randomly divided into two treatment groups of DN (n=20) and SWT (n=20). Visual analog scale for the pain assessment, Lower Extremity Functional Scale (LEFS) for the function evaluation, and length of the iliotibial band were assessed at baseline, immediately after the cessation of the intervention, and within four weeks. Results: The two groups were similar regarding demographic characteristics (P0.05). Both approaches could efficiently lead to improved pain (P0.001) and promoted function based on LEFS (P0.001); however, iliotibial band length (ITBL) did not alter remarkably (P0.05). The groups were similar in terms of pain score, LEFS, and ITBL at all of the assessment intervals (P0.05), but the pain score within four weeks following the interventions that were significantly better in DN (P=0.023). Conclusion: Based on our results, DN, as well as SWT, could remarkably lead to an improvement in pain and function among patients resenting from ITBS; however, none of the approaches was superior over the other. IIliotibial band syndrome (ITBS) is a leading cause of pain complaints in the lateral aspect of the knee and is mostly notified in runners . ITBS is1. Study Population This randomized controlled clinical trial was conducted on 40 patients diagnosed with ITBS and referred to the Physical medicine and Rehabilitation outpatient clinics affiliated with Isfahan University of Medical Sciences from May 2018 to August 2019. The study protocol was approved by the Ethical Committee of Isfahan University of Medical Sciences (code number: IR.MUI.MED.REC.1398.161).Besides, this report as a phase 3 trial was proposed for the Iranian Registry of Clini¬cal Trials and legislated based on the code IRCT20190824044598N1. The protocol was explained to the patients, they were reassured about the confidentiality of their personal information, and written consent was obtained. Patients (ranged 18-60 years old) with documented ITBS diagnoses who had normal neurological examinations were included. ITBS was diagnosed by an expert physical medicine and rehabilitation specialist according to the clinical physical examination, positive Ober's test, and the presence of the least one trigger point on an ITB. Any fracture in thigh, knee, or shin or any surgical procedure on the affected knee within the last 12 months, application of any thera¬peutic intervention to control the chronic knee pain  within two months, and the use of NSAIDs for over two weeks before the interventions, radiculopathies, coagulopathy, and anticoagulant agents use were considered the unmet criteria. Reluctance to participate in the study, over 20% defects in the medical records, and failure to participate in reassess¬ments were the exclusion criteria of the current study. Convenience sampling was administered to include the studied population. After that, the participants were randomly allocated to DN therapy and SWT using Random Allocation Software . Therefore, the patients with odd numbers were allocated to DN therapy and those with even numbers to the shockwave therapy. The person who gathered the data about the outcomes of the interventions was blinded to the type of treat¬ment. 2. Interventions The trigger points were primarily found based on pincer palpation on the lateral aspect of the thigh and lateral femoral epicondyle. To keep the location of the trigger points between the sessions of interventions, a 10*10 cm centrally perforated piece of a paper was administered . 2.1. DNIn the current study, the eligibility of 48 cases with the diagnosis of ITBS has been evaluated; among them 40 patients met the criteria for participation in the study and were randomly allocated to the DN therapy n=20) and SWT (n=20, Figure-0 and SWTThe current study was conducted to compare the efficacy of SWT versus DN to manage cases with ITBS. The two assessed groups were similar in terms of demographic charac¬teristics; therefore, the possible confounding role of these factors is eliminated, and the results are dedicatedly contributed to the treat¬ment approach. Both treatments could properly improve the pain and LEFS, but not ITBL. The comparison of DN versus SWT generally revealed that the approaches were non-inferior over the other; however, those under the DN approach experienced significantly less severe pain in the four-week follow-up investigation. Limited studies in the literature have com¬-pared DN versus SWT. Walsh et al.  com¬pareBased on this study, DN and SWT could remarkably improve pain and function among patients resenting from ITBS; however, our outcomes revealed non-inferiority of each approach over the other. To generalize the outcomes, further studies with a more extended follow-up period are recommended.The authors of this manuscript want to acknowledge Dr. Ali Safaei for his efforts in conducting and preparing the current study.The authors of the current study declare no conflict of interest.


Pre-existing chronic pain has been associated with severe postoperative pain. In this study, we sought to prospectively analyse the association between the duration of chronic low back pain and the intensity of acute postoperative pain after lumbar fusion surgery.A total of 330 patients who underwent lumbar fusion surgery were divided into three groups  based on the duration of chronic pain. On the first postoperative day, the maximum pain scores of each patient were recorded during the day and at night. Bivariate correlation and logistic regression were performed to identify relationships between acute postoperative pain and related variables . If the postoperative pain score was > 3 when the patient reported was at rest, the patients were treated with postoperative intravenous self-controlled analgesia or rescue analgesics if necessary.p = 0.0789). The result is uncertain because the confidence interval included the null after controlling for SAS, SDS, BMI, and aetiology of back pain. In terms of VAS night, patients with a duration of chronic low back pain of more than 5 years were more likely having moderate to severe acute postoperative pain (VAS > 3) compared to patients with a duration of chronic low back pain less than 1 year . Hospital stay, the pain score on the day of discharge and the pain score after 3 months displayed no significant difference among the three groups (P > 0.05). However, the need for postoperative rescue analgesics was different among the three groups (P < 0.05).There was an association between severe acute postoperative pain and the duration of chronic low back pain. In terms of VAS day, multivariable logistic regression showed the duration of chronic low back pain was not statistically significant .This study was registered at the Chinese Clinical Trial Registration Center ( Low back pain is one of the most frequent reasons people seek medical services . It not In the past two decades, the number of patients choosing lumbar fusion surgery due to lumbar degenerative diseases has been increasing worldwide . ClinicaTherefore, in the present study, we investigated whether the duration of chronic low back pain influences the acute postoperative pain of patients undergoing lumbar fusion surgery. The visual analogue scale (VAS) is a tool used to assess postoperative pain. Our aim was to provide a reference for the pain management of patients with chronic low back pain.This study was approved by the ethics committee of the Chinese Ethics Committee of Registering Clinical Trials with approval number ChiECRCT20200165. The participating patients provided written informed consent. All methods were carried out in accordance with the Declaration of Helsinki and with the STROBE recommendations. This study was registered at the Chinese Clinical Trial Registration Center under the number ChiCTR2000029923 before patient enrolment. After obtaining written informed consent from all patients, we conducted this prospective observational study at The First Affiliated Hospital of USTC from July 8, 2020, to December 1, 2020. The inclusion criteria were as follows: patients with American Society of Anaesthesiologists (ASA) grades I to III, age range of 18 to 75 years, chronic low back pain supported by a focused history, physical examination and lumbar imaging by X-ray, magnetic resonance imaging, or computed tomography . These preoperative examinations were conducted by clinicians. Patients with low back pain unresponsive to conservative treatment for more than 3 months and planned to undergo two-level open lumbar fusion surgery under general anaesthesia  were included. The exclusion criteria were as follows: patients who refused to participate or who had cognitive impairment (unable to provide informed consent); other chronic pain conditions ; took analgesic drugs before surgery (gabapentinoids and/or NSAIDS) or had a history of opioid abuse; chronic low back pain not due to spinal stenosis, spondylolisthesis; or disc herniation but manifested by one or more specific causes ; previously underwent lumbar spine surgery; chronic opioid or gabapentin treatment or a visual analogue scale score of > 3 over the past week .Patients were evaluated from hospital admission until 3 months after discharge by the same investigator who was blinded to the design of the trial. The evaluator introduced the questionnaire and scoring rules to each patient in detail. The online questionnaire was used to record the clinical information via a tablet. Before surgery, the age, sex, smoking history, body mass index (BMI), operation history, duration of surgery, level of preoperative pain , aetiology of back pain , Self-rating Anxiety Scale (SAS), Self-rating Depression Scale (SDS), FRAIL scale, and duration of chronic low back pain were recorded online by an anaesthetis. According to their chronic low back pain duration, the patients could be classified into three groups: duration of pain less than 1 year, one to 5 years, and more than 5 years. We conducted a unified general anaesthesia program. The VAS (ranging from 0 to 10) was used to evaluate the acute postoperative pain (maximum intensity) during the day (VAS day) and night (VAS night) on the first postoperative day after surgery. All patients were treated with postoperative intravenous self-controlled analgesia (PCIA). The PCIA contained 100 μg of sufentanil and 98 mL of saline. The analgesic pump was set as follows: background infusion of sufentanil 2 μg/h, bolus dose of sufentanil 2 μg, and lockout interval 10 min. Patients pressed the PCIA when they experienced pain at rest > 3. If patients still reported pain or greater than 4 on a 0–10 scale on the VAS, supplemental rescue boluses of intravenous flurbiprofen axetil injection of 50 mg were administered. The patient’s analgesic dosage , pain scores on the day of discharge, pain scores after 3 months, and hospital stay were recorded.To achieve a sufficient sample size, we used PASS software to calculate the power. We first conducted a preliminary experiment, and the means of the maximum pain score (VAS) of the three groups  during the day were 2.60, 2.90, and 3.20, respectively. The SDs of the maximum pain score of the three groups during the day were 0.88, 0.85, and 0.83, respectively. The significance level (α) was set at 0.05 and power (1-β) = 0.98. In the one-way ANOVA in PASS software, the sample size required for each group was 79. The mean maximum pain scores (VAS) of the three groups during the night were 3.55, 3.85, and 4.10, respectively. The SDs of the maximum pain score of the three groups during the day were 0.95, 0.88, and 0.85, respectively. The sample size was calculated in the same way, and the number of patients required for each group was 101. Considering a certain loss to follow-up, the sample size of each group was set to 110.The preoperative mental state was evaluated on the day before surgery using the Chinese-language versions of the SAS and SDS. The SAS and SDS are self-report questionnaires that provide a comprehensive assessment of the anxiety and depression status of patients . The SASThe VAS  is a tool used to assess pain levels . It is oThe FRAIL scale , 22 is aP < 0.1 in the bivariate correlation analysis were included in the binary logistic regression for further analysis. Logistic regression models were used to examine the effect of some independent variables on acute postoperative pain (VAS day and VAS night). According to the degree of postoperative pain scores, we converted the measurement data into dichotomous data [p < 0.20 in univariate logistic regression) put into the multivariable logistic regression model. After the stepwise model selection, only risk factors with p < 0.10 were kept in the final logistic regression model. Odds ratios with 95% confidence intervals were reported based on the regression models. A significant difference between different groups and a significant correlation of variables were set at P < 0.05.Statistical calculations were performed using IBM SPSS Statistics Version 22. Descriptive analysis was performed to identify the number and percentage of demographic characteristics. Data are shown as the mean ± standard deviation (SD) or number (%). One-way ANOVA and the chi-square test were used to identify the differences among the three groups in the baseline demographic variables , SAS scale, SDS scale, FRAIL scale, duration of surgery, aetiology of back pain). Bivariate correlation analysis  , operation history, smoking history, duration of surgery, SAS, SDS, aetiology of back pain, and FRAIL scale were all recorded as the baseline before surgery. Initially, 332 patients consented to participate in this prospective trial but. 1 patient was lost to follow-up and, 1 patient changed to a different surgical procedure. Data from the remaining 330 patients were included in this analysis. The number and percentage of these items were used to describe and measure the patient demographics in the three groups, as shown in Table P < 0.1 were level of preoperative pain , SAS , SDS , and duration of chronic low back pain , which were correlated with VAS day. The independent variables with P < 0.1 were level of preoperative pain , SAS , SDS , and duration of chronic low back pain , which were correlated with VAS night  and the duration of chronic low back pain or other variables. In the bivariate correlation analysis, age, sex, BMI, level of preoperative pain (VAS), operation history, smoking history, duration of surgery, SAS, SDS, FRAIL scale, aetiology of back pain, and duration of chronic low back pain (three groups) were included. Ultimately, the independent variables with ht Table .Table 2Bp = 0.0789)  showed statistical significance in univariate analysis, but it was not included in the final multivariable model, it could be due to the interactions or correlations among variables. SAS and SDS showed statistical significance in both univariate logistic regression and multivariable logistic regression. After controlling SAS, SDS, BMI, and aetiology of back pain, the duration of chronic low back pain did not show statistical significance. The result is uncertain because the confidence interval included the null after controlling for SAS SDS, BMI, and aetiology of back pain  Table .Table 3Up = 0.0074)  showed statistical significance in univariate analysis, but it was not included in the final multivariable model. SAS and SDS still showed statistical significance in both univariate logistic regression and multivariable logistic regression. After controlling SAS and SDS, the duration of chronic low back pain is showed statistically significant. Patients with a duration of chronic low back pain of more than 5 years were more likely having moderate to severe acute postoperative pain (VAS > 3) compared to patients with a duration of chronic low back pain less than 1 year , hospital stay  not reported in our study, and these factors may be associated with acute postoperative pain intensity. Third, this is a single-centre, relatively small population trial, and a multicentre trial is necessary to verify the results.For patients with a history of chronic low back pain who underwent lumbar fusion surgery, the longer the preoperative pain lasted, the higher the incidence of moderate to severe acute postoperative pain and the more analgesic drugs required after surgery. Therefore, it is very important to pay attention to patients’ chronic pain before surgery, especially the duration of chronic pain. Patients with long-lasting chronic pain should undergo stricter analgesia treatment supervision after surgery to prevent them from suffering from more severe pain.


Therefore, we delineated the clinical alterations in patients of CP/CPPS that might be attributed to the functional abnormality of the thalamus, inferior parietal lobule, and cingulate gyrus. Among these regions, the PAG, thalamus, and SFG may further play an important role in the pathogenesis, with their regulating effect on pain or emotion.Chronic prostatitis/chronic pelvic pain syndrome (CP/CPPS) is a challenging entity with complicated symptoms for treatment in the male crowd. Accumulating evidence revealed the dysfunction in the central system should be a critical factor for the pathogenesis and development in the CP/CPPS. Therefore, we recruited 20 patients of CP/CPPS and 20 healthy male volunteers, aged 20 to 50 years. Through resting-state functional magnetic resonance imaging (fMRI), we analyzed the mean amplitude of low-frequency fluctuations (mALFF) and the mean fractional amplitude of low-frequency fluctuations (mfALFF) to reflect the spontaneous abnormal activated regions in the brains of CP/CPPS patients. Compared to the healthy controls, the group with CP/CPPS had significantly increased mALFF values in the thalamus and augmented fALFF values in the inferior parietal lobule and cingulate gyrus. Significant positive correlations were observed in the extracted mALFF values in the midbrain periaqueductal gray matter (PAG) and the pain intensity ( Chronic prostatitis/chronic pelvic pain syndrome (CP/CPPS) is one of the most common disorders in the daily clinic of urology, which occupies approximately 90–95% types of chronic prostatitis . On the Although in the past decades many different etiologies and mechanisms of pathogenesis of CP/CPPS have been proposed, the pathogenesis of CP/CPPS remains unclear . A mass Because CP/CPPS belongs to a kind of chronic pain disorder, central sensitization mechanisms, such as neuromodulation and reorganization in the brain, have been proven to concern the pathophysiological progresses . RestingThe spontaneous low-frequency  oscillations (LFOs) of the human brain are thought to reflect the changes in spontaneous neuronal and physiological activities to a certain extent . The ampOur previous work revealed that altered functional connectivities in the patients with CP/CPPS might play a vital role in the pathogenesis and development of CP/CPPS by analyzing the integrity of the default mode network (DMN) . We postWe actually recruited a cohort of 20 male right-handed patients with spontaneous pelvic pain caused by chronic prostatitis/chronic pelvic pain syndrome and 20 healthy right-handed, age- and gender-matched controls . The patNIH-CPSI scale. The NIH-CPSI was an objective assessment tool and outcome measurement for prostatitis-like symptoms in the management of men with CP/CPPS since 1999 , for eliminating the difference in the time in differentiated fMRI signal levels, and the signals were calibrated as if they were obtained at the same time point; (3) head motion correction; (4) normalization, transforming the brain images to reduce the variability between individuals and allowing meaningful group analyses by using T1 image unified segmentation, with bounding box  and isotropic voxel size [All the DICOM files in format were converted to NIFTI files by MRIconvert  value to standardize the data. The procedure of data analysis of fALFF was similar to ALFF. After taken as the ALFF, the amplitude of the current band (0.01–0.08 Hz) divided by the amplitude of the full band (0–0.25 Hz), which made the fALFF and mean fALFF (mfALFF).p < 0.01, cluster p < 0.01). The statistical images were superimposed on the standard spatial template for presentation. Active clusters larger than 100 voxels were illustrated in the calibrated standard brain map with pseudo-color, and their Montreal Neurological Institute (MNI)coordinates, positions, and voxel sizes of peak intensity were listed in a table reported by XjView95 software ); significant difference was set at p < 0.05. The abnormal brain regions were respectively set as the regions of interest (ROIs). Linear regression analysis was conducted with SPSS 11.0 as dependent variables to the scores of clinical scales and the relative intensity values extracted from ROIs. The significant difference was set at p < 0.05. The outcomes of linear regression analysis were displayed by GraphPad 8.0.A two-sample t-test was conducted based on the measured data of clinic scales or other basic information  by SPSS 17.0, and results were scheduled as X¯ ± S . A two-sp = 0.1497). To elude the potential impact from senile brain atrophy, the age ranges of the participants were set from 20 to 50 years old. The baseline for the duration of spontaneous pelvic pain was about 20 months, which was consistent with the foundational description of CP/CPPS.As demonstrated in The mean scores of the total NIH-CPSI were approximately 28, which revealed that the participated patients with CP/CPPS endured a severe disease condition when the scores were over 18. Because the counted scores of the NRS in the cohort with CP/CPPS were 3.50 ± 2.35, the pain degrees of spontaneous pelvic pain were between mild and moderate states. Moreover, the NRS also assisted us to eliminate the potential chronic pain patients in the confirmation of healthy volunteers. The scores of the HADS subscale will be valuable if the corresponding score is over 7, so the patient cohort presented the psychological feature of anxiety with the mean scores of the HADS anxiety subscale (9.44 ± 5.54). The relatively low mean scores of the HADS depression subscale may be because of a short disease course and outpatient bias. Hereafter, subsequent attention will be paid to the psychological situation of anxiety rather than depression in the CP/CPPS participants.As the altered clusters were illustrated in As demonstrated in r = 0.2712, p = 0.0019), which revealed the abnormality of the PAG affected the pain degrees of the CP/CPPS patients with spontaneous pelvic pain. As presented in r = 0.08477, p = 0.0461), which implied that the emotional changes in the cohort of the CP/CPPS patients might attribute to the impact of the altered function in the thalamus. Similarly, as demonstrated in r = 0.07102, p = 0.0461), which hinted the anxiety symptoms in the participated patient group would also refer to the alterations in the identified SFG.The values of the mALFF and mfALFF were extracted in the correspondingly picked clusters. As exhibited in CP/CPPS are the most common types of urological diseases in the male population, which generates several challenging issues, such as an obscure pathogenesis, a lack of effective therapies, high recurrence rates after treating, emotional symptoms, the low life qualities of patients, and a heavy social burden . In receAs illustrated in The clusters in the thalamus were the majority in the altered brain regions in the analysis of the mALFF. As a part of the limbic system, the thalamus was recognized as an important node to modulate the ascending nociceptive information in the chronicity of pain . SeveralCompared to the healthy control, this cluster also covered parts of the putamen, parahippocampal gyrus, right pallidum, etc. These pain-related regions also got involved in the changes in emotion and pain intensity. Likewise, the putamen participates in the sensory-discriminative parts of pain, and the increased function of the putamen may explain the clinical pain and motor impairment in patients with complex regional pain syndrome . The parIn As a crucial number of emotional arousal networks, the superior frontal gyrus is crucial for self-awareness and sensory and emotional processes . ParticuWe should mention there are some limitations in this study. Firstly, the participants we selected in the patients group revealed anxious symptoms, which may not cover all the emotional morbid states in the CP/CPPS. Secondly, the sample size was relatively small. The small sample size may have limited the statistical power. Then, as observational research, we did not design any intervention to assess the relationship between the abnormal brain regions and clinical prognosis. Finally, we should design an extensive study for investigating the central mechanisms of CP/CPPS for further research.In conclusion, the ALFF and fALFF analysis of the resting-state fMRI revealed an abnormal pain perception system and emotional arousal network may be responsible for the symptoms of pain and anxiety in CP/CPPS. These finding could be potential parameters for assessing the severity of CP/CPPS and prospective biomarkers for further clinical observation before and after intervention.


It seems that nonspecific low back pain (NSLBP) cannot be successfully treated with a single intervention of any kind. However, a positive effect of an active lifestyle including physical activities in NSLBP is reported on pain and disability. Advising regular physical activity is one of the mainstays in physical therapy treatment, appealing to patients' adherence. Many patients with low back pain do not seem to adhere to their physiotherapist's advice. In this study, the influence of social support on adherence to an activity advice will be investigated.Objective of the study is to investigate if patients with low back pain randomised to receive social support adhere better to an activity advice than patients randomised to the control group.In a randomized controlled clinical trial, in private physiotherapy practices in the Netherlands, patients ≥18 years presenting with at least a second episode of nonspecific low back pain will be randomized over two groups: activity advice and social support as an add‐on to usual care versus usual care alone. The primary outcome measure is adherence to an activity advice measured by an activity monitor at 1, 6 and 12 weeks. All other objectives will be measured by questionnaires.This project is the first comprehensive research project to assess whether social support influences adherence to an activity advice outside the clinical setting without supervision of a healthcare provider. Where evidence of influence on social support is lacking, findings may have implications for the management of patients with low back pain. In addition, findings may enable physiotherapists to predict in which patients with low back pain an activity advice with social support makes sense.NCT02996955. Dutch people have access to their physiotherapist without a referral of their GP. People with an additional insurance are compensated for the costs. For this study physical inactive patients with low back pain are needed. It is hypothesized that patients having more than one episode of NSLBP are potentially more inactive compared to patients with a first episode, therefore patients with a first episode of low back pain will be excluded. Patients ≥18 years presenting with a self‐reported second episode (or more) of NSLBP are recruited for the study. Eligible patients will be recruited for the study together with their partner or friend. Patients will be excluded for the study if (1) they cannot bring a partner or friend, (2) they are unable to read, write or speak the Dutch Language, (3) they present red flags as mentioned in the Dutch low back pain guideline  being a certified graduate physiotherapist, (2) being instructed and updated on the content of the study.During the first meeting all physiotherapists will be informed about the Dutch guideline for low back pain  Appendix . The CIRIt is hypothesised that overweighted/obese patients are protentional physical inactive. BMI of the patient will be calculated and categorized according to the WHO criteria WHO, .It is hypothesised that the number of recurrences of low back pain influence adherence to an activity advice negatively, therefore, the number of recurrences of periods of low back pain will be noted.To assess whether perceived pain and/or disability influences adherence to the activity advice, the visual analogue scale (VAS) for pain and the Quebec Back Pain Disability Scale (QBPDS) for disability will be used at baseline, both of which have been validated for assessing pain and disability . During the assessment periods at one, six‐ and 12‐week patients are instructed to wear the Activ8 every day during one week. The number of days per week patients have walked or cycled according to the advice will be counted. Cut‐off for adherence will be set at a minimum of 5 times per week of at least 30 min walking and/or cycling. The Activ8 system is a valid instrument to quantify body postures and motions  assesses patients' and partner/friends' illness beliefs Appendix . Eight iThe module attitude and intention (MAI) of The Knowledge, Attitude, Self‐efficacy and Self‐regulation, Exercise and Social Support for Sports and Exercise Questionnaire will be used to assess attitude and intention to be physically active  of 80%, 142 patients are needed. With an expected overall drop‐out rate of 15%, a total of 163 patients is needed.2.6Recruitment is scheduled from October 2016 till December 2022. To achieve adequate patient enrolment, next to own consultation of patients experiencing non‐specific low back pain by participating physiotherapists, referring health care providers, such as general practitioners located in the city of the participating practices will be informed about the study, to send patients with non‐specific low back pain to those physiotherapists.2.7It is hypothesised that patients in the intervention group adhere better to the activity advice than patients in the control group. It is also hypothesized that patients having a BMI >25 and patients experiencing >3 episodes of NSLBP are potentially more inactive and non‐receptive to the interventions on adherence. To prevent influence of these factors on study outcomes, stratification is applied on these variables. Therefore, a concealed randomization sequence is prepared by the randomisation centre of the Maastricht University. Randomization will be performed with a block size of four, with strata for BMI  and number of previous episodes of low back pain .Investigators, patients, partners or friends and participating physiotherapists are blinded to the allocation and outcomes. To prevent that patient and their partners/friends of both groups will meet in the waiting room appointments of patients treated in the intervention or control group in the same private practice must be planned on different days or sections of the day. Physiotherapist are blinded for participating in the intervention group or control group. To ensure blinding of the physiotherapists, where their training is separate, it will be emphasized not to communicate about the interventions to each other during the investigation period.2.8Patient data will be coded and the key to the codes will be safeguarded by the secretary of the randomization centre of the Maastricht University. These codes are unknown and not accessible for the researchers. Outcomes of questionnaires and Activ8 will be collected by the assessing physiotherapist. Losses‐to‐follow‐up and respective reasons will be recorded. The researchers collect the data from the assessors every month and enter the data in an electronic database. Access to the data obtained in this research will be restricted to the researchers involved in the collection and analysis of the data. The handling of personal data complies with the General Data Protection Regulation (GDPR) EU, . Study f2.92 test will be used to investigate if there is a significant difference in the proportion of adherent patients to the activity advice between the intervention and control group after one, six and 12 weeks, and if there is a significant difference in the proportion of adherent patients between patients who experienced social support or not on the social support scale after 12 weeks. A Time Series Analysis will be used to present changes over time in perceived illness beliefs of patients and partner/friend. To understand whether illness beliefs influence adherence, Pearson's r between outcomes of the IPQ‐S at baseline and after 12 weeks and (non)adherence measured by the Active8, will be calculated, and linear regression will be used for modelling the relationship between these outcomes. To assess the correlation between attitude and intention to physical activity (MAI) and adherence at 12 weeks, Pearson's will be calculated, and linear regression will be used for modelling the relationship between these outcomes. Influence of age, gender, education level, comorbidity (CIRS), pain (VAS) and disability (QBPDS) on adherence, will be estimated by multiple regression analyses. A p value of <0.05 will be considered statistically significant.To analyse the data SPSS version 25.0  will be used. For demographic data descriptive statistics will be used and normality assumptions for the variables will be checked. An intention‐to‐treat analysis will be used for the main outcome. To correspond to the primary aim of the study, outcomes of the Activ8 will be dichotomized into adherent and not adherent patients in the intervention and control group. The Chi2.10Regular walking and cycling are not associated with adverse effects for NSLBP; there is no formal proof that any of these physical activities have harmful effects. The social support and treatment of illness beliefs described in this study are designed for better outcomes of physical activity levels and have no proven negative influence on pain and disability in NSLBP sufferers. Patients in both groups receive concomitant best evidence healthcare according to the Dutch guideline for low back pain  and has been approved by The Central Committee on Research Involving Human Subjects (CCMO), named METC Zuyderland‐Zuyd with Approval Number NL58005.096.16.All amendments, protocol deviations and SUSAR's will be notified to the METC Zuyderland‐Zuyd. The investigator will notify the METC Zuyderland‐Zuyd of the end of the study within a period of 8 weeks. The end of the study is defined as the last patient's last visit. In case the study is ended prematurely, the investigator will notify the METC Zuyderland‐Zuyd within 15 days, including the reasons for the premature termination. Within 1 year after the end of the study, the investigator will submit a final study report with the results of the study, including any publications/abstracts of the study, to the METC Zuyderland‐Zuyd.This research does not receive any specific grant from funding agencies in the public, commercial, or non‐for‐profit sectors. This paper presents independent research for which no conflicts of interest are to declare.3This project is the first comprehensive research project to assess whether social support influences adherence to an activity advice outside the clinical setting without supervision of a healthcare provider. Unique in this study is that intervening on illness beliefs will be provided to patient and partner to minimize the influence of maladaptive illness beliefs on adherence. Literature mentions that intervention on illness beliefs changes outcomes of the DIPQS, however, responsiveness of the questionnaire is lacking adherence are operationalized in existing literature resulting in variable outcomes (Essery et al., Strengths of the study are the concealed allocation and the randomization. To reduce the presence of observer bias, measurements will not be performed by the treating physiotherapist.Treatment of both groups in one physiotherapy practice is preferred to overcome selection bias. This implicates that despite the standardized protocol and the strict requirements to ensure blinding, it is possible that patients and treating physiotherapist exchange information about the interventions. This may influence outcomes and is therefore a limitation of the study.4When effectiveness of social support on adherence in NSLBP patients is demonstrated, in a patient centred approach, it can help to achieve patients' health goals.A simple low‐cost intervention, not requiring additional education, can be added as a treatment option to increase patient relevant outcomes.Ben van Koppen, is a first author, Pim Zandwijk is a second author and Henk van Mameren, Rob de‐Bie are guarantor of the study protocol.This paper presents independent research for which no conflicts of interest are to declare.All amendments, protocol deviations and SUSAR's will be notified to the METC Zuyderland‐Zuyd. The investigator will notify the METC Zuyderland‐Zuyd of the end of the study within a period of 8 weeks. The end of the study is defined as the last patient's last visit. In case the study is ended prematurely, the investigator will notify the METC Zuyderland‐Zuyd within 15 days, including the reasons for the premature termination. Within 1 year after the end of the study, the investigator will submit a final study report with the results of the study, including any publications/abstracts of the study, to the METC Zuyderland‐Zuyd.Not applicable.Not applicable.The study is registered at ClinicalTrial gov NCT02996955.Supplementary MaterialClick here for additional data file.


Quadratus lumborum block (QLB) is a fascial plane block. There is no randomized study on the efficacy of QLB for lumbar surgery. We evaluated the efficacy of QLB for postoperative pain management and patient satisfaction after lumbar disc herniation surgery (LDHS).n = 30) or the control group (n = 30). QLB was performed with 30 ml 0.25% bupivacaine in the QLB group. Paracetamol 1 g IV 3 × 1 was ordered to the patients at the postoperative period. If the NRS score was ≥ 4, 1 mg/ kg tramadol IV was administered as rescue analgesia.Sixty patients with ASA score I-II planned for LDHS under general anesthesia were included. We allocated the patients into two groups: the QLB group (p < 0.05). There was no difference in the resting NRS at any other time point up to 24 h. The median dynamic NRS was significantly lower at 0, 2, 4, 8, and 16 h in the QLB group (p < 0.05). The need for rescue analgesia was significantly lower in the QLB group. The incidence of nausea was significantly higher in the control group. The postoperative patient satisfaction was significantly higher in the QLB group (p < 0.05).There was a reduction in the median static NRS at 0 h and 2 h with QLB compared to the control group (We found that the QLB is effective for pain control following LDHS. Lumbar disc surgery is a common procedure performed for leg and lower back pain. It commonly provides satisfactory results for most patients , 2. HoweUltrasound (US)-guided regional anesthesia methods have recently become popular in daily anesthesia practice, and they have great potential to support effective postoperative pain management , 7. A USEthical approval for this randomized prospective study was provided by the Istanbul Medipol University Ethics and Research Committee . After approval, the trial was added to a clinical trial registry (NCT04981301. First registration date is 28/07/2021). American Society of Anesthesiologists status 1–2 patients aged between 18 and 65 years scheduled for elective single-level lumbar discectomy and hemilaminectomy surgery under general anesthesia were enrolled in the trial. The study procedure was explained to the patients and their written informed consent was obtained. When enrolling the patients, we followed the steps of the Consolidated Standards of Reporting Trials (CONSORT) flow diagram  or the control group (n = 30).The exclusion criteria were coagulopathy, anticoagulant treatment, history of local anesthetics, allergy, localized infection in the block procedure area, pregnancy or breastfeeding, inability to understand or use the verbal-rated pain-scoring system, and refusal to participate in the study. Using a computerized randomization program, we allocated the patients to one of two groups: the QLB group , fentanyl (1–1.5 µg/kg), and rocuronium bromide (0.6 mg/kg) IV was used for classical anesthesia induction. The patients were placed in the prone position following intubation for surgery. Sevoflurane with a mixture of oxygen + fresh air, and remifentanil (0.5 – 1 µg/kg/min) infusion was used for anesthesia maintenance. All patients underwent unilateral single-level lumbar microdiscectomy/hemilaminectomy surgery by the same surgical team using the same technique. The wound size was 12 mm routinely. Paracetamol (1 g) and a dose of 100 mg tramadol were intravenously administered to all patients 30 min before the end of the surgery for postoperative analgesia. Moreover, the patients were given 4 mg ondansetron to prevent nausea and vomiting. The QLB was performed at the end of the surgery before extubation. In the control group, a dose of 0.25% bupivacaine (30 ml) was injected for skin analgesia by the surgeon around the surgical area. Patients with sufficient spontaneous respiration were extubated and then transferred to the post-anesthesia care unit (PACU).The QLB was performed using US  at the end of the surgery before extubation, with patients in the prone position. Under aseptic conditions, the convex transducer was covered with a sterile sheath. The transducer was placed just above the iliac crest and moved cranially to visualize the three abdominal muscles, psoas muscle, and the QL muscle Fig. . A 22 g,In the postoperative period, 1 g paracetamol was administered intravenously every 8 h. Patients were evaluated by a pain nurse who did not know how the patients were grouped. The patients were blinded with regards to the treatment received. Their postoperative pain was assessed using the 11-point Numerical Rating Scale (NRS), which ranges from 0 (meaning “no pain”) to 10 (meaning “worst pain imaginable”). The NRS scores were recorded at rest (static) and during mobilization (dynamic) at 0 (PACU), 2, 4, 8, 16, and 24 h. If the NRS score was ≥ 4, 1 mg/ kg tramadol IV was administered as rescue analgesia. Adverse effects such as nausea, vomiting, and itching were recorded. Patient satisfaction was assessed with the Likert scale.The primary outcome was the dynamic pain score in the PACU (during a motor power assessment test) postoperatively. Pain scores were assessed using the NRS.The secondary outcomes were the need for rescue analgesia, adverse effects, and the measurement of patient satisfaction, as recorded during the initial 24-h postoperative period. The need for rescue analgesia was evaluated as “used” or “not used” (yes/no). The incidence of nausea/vomiting/itching was assessed as “yes” or “no.” Patient satisfaction related to postoperative analgesia was evaluated using a seven-item Likert scale .A preliminary study was performed on eight patients from each group in our clinic. We considered a reduction in mean pain scores (dynamic NRS in the PACU) by two points to be clinically meaningful and important. For a two-sided test, assuming a mean (SD) pain score of 4.5 (2) in the control group, a sample size of 29 per group had a power of 85% to detect a statistically significant difference in mean pain scores of two or more using Student’s t-test, with the alpha set to 0.05 and the sample size estimated using the G*Power 3 analysis program .The shape of the distribution of the variables in this study was assessed using the Shapiro–Wilk test, to determine whether the observations were normal or skewed. In cases where the test results indicated that the data were normally distributed, the data were presented with the mean ± SD and analyzed using an independent samples t-test to compare groupwise differences in the outcome parameters. Meanwhile, we presented continuous data that yielded a non-parametric dispersion with the median and IQR, and we analyzed these using the Mann–Whitney U test to observe the groupwise differences. Statistical analyses were conducted using SPSS V.25 .We recruited 60 patients, with 30 allocated randomly to each group during the study period. Demographic data are shown in Table p = 0.001 and 2  vs. 2 , p = 0.003, respectively; p = 0.001 and p = 0.003, respectively). There was no difference in the resting NRS scores at any other time point up to 24 h (Table We found a reduction in the median (IQR [range]) static NRS scores at 0 h and 2 h with QLB compared to the control group . The incidence of nausea was significantly higher in the control group compared to QLB . There were no differences in terms of vomiting or itching . The postoperative patient satisfaction  was significantly higher in the QLB group compared to the control  and reduced their need for rescue analgesia. Furthermore, patient satisfaction was higher in the QLB group.The QLB was first described by Blanco, and since then, it has been modified and different approaches with different needle trajectories described –10. The There are three approaches to the QLB in the current literature –12. The The QLB is a safe, effective fascial plane block that is easy to apply. According to our results, an anterior QLB may be a good analgesic option for lumbar spine surgery. We followed the patients in this study for 24 h and recorded lower pain scores and less of a need for rescue analgesia in the QLB group. The median duration of analgesia after the QLB exceeded 16 h, but that duration may have depended on the volume we used . In the literature, the volume used for the QLB is often 40 ml. Since fascial plane blocks are volume-dependent, the analgesic period may have been longer if we used a higher volume than 30 ml. Though our study did not focus on the dermatome level, the pain relief in the QLB group showed that the QLB provided analgesia after LDHS. Though the QLB is safe, potential unintended complications such as abdominal organ injury and hematoma should be kept in mind , 20. In Our study has some limitations that must be noted before we conclude. Firstly, we used a single total volume of 30 ml local anesthetic, though different results may be achieved with different volumes. Secondly, we used only an anterior approach to the QLB, creating a need to investigate other approaches to the QLB for lumbar spine surgery. Lastly, we did not evaluate the dermatome level after the block’s application. In this research, we evaluated the efficacy of the QLB based on the patients’ pain scores and need for rescue analgesia, but in the future, larger studies are needed to corroborate our findings on the efficacy of the QLB after LDHS.In conclusion, according to the results of our study, an anterior QLB lowers patients’ postoperative pain scores and reduces the need for rescue analgesia. Overall, we found that the QLB is effective for pain control following LDHS.