IntroductionNeuromodulation is an evolving and increasingly popular therapy for chronic pain management. Recent data suggest that novel waveforms have demonstrated greater benefit over traditional spinal cord stimulation (SCS). The authors conducted a retrospective review of patients undergoing high-frequency 10 kHz SCS at a single tertiary medical center for the purpose of contributing further evidence to this growing body of data. The literature of high-frequency SCS published to date was also reviewed.MethodsA retrospective chart review was performed for patients with chronic pain syndrome, including failed back surgery syndrome and sciatica alone, who underwent high-frequency SCS at 10 kHz. This data was analyzed using R software  for statistical analysis. The PubMed database was searched for relevant articles using the search terms “high frequency,” “10 kHz,” and “spinal cord stimulation.” All relevant studies conducted to date were included in this literature review.ResultsTwenty-one patients had complete follow-up data and were included in this study. Of the 21 patients, 85.7% subjectively reported post-operative pain relief while 71.4% of the total patients reported pain relief by ≥ 50%. There was a statistically significant decrease in mean VAS scores from pre-operative to 12-months post-operative . Additionally, 76.5% of patients subjectively reported improvements in sleep and activities of daily living. Recent studies indicate that high-frequency SCS appears to be a viable option for delivering quality pain relief in patients for chronic regional pain syndrome, failed back surgery syndrome, sciatica, and also pain in the upper cervical region of the spine.ConclusionThis article provides evidence both with the authors’ own institutional data and from the currently published literature for the efficacy of using high-frequency SCS at 10 kHz as a first-line programming option for patients undergoing SCS. Chronic pain is a widely prevalent and debilitating health condition with a total financial cost reported to range from $560 - $635 billion -3. NeuroA recent major advancement has been the ability to modulate higher frequency and faster waveforms for SCS, which has shown diverse levels of effectiveness in controlling chronic pain without eliciting the sensations of paresthesia that lower frequency waveforms can create ,6,7. ThuTherefore, the authors conducted a retrospective review of their institutional records for patients implanted with HF10-SCS as a first-line stimulation programming option in patients who have not undergone traditional SCS. Through this review of a single surgeon experience, pain relief, changes in sleep, changes in the use of pain medications, and changes in activities of daily living were measured and statistically analyzed. The literature on high-frequency spinal cord stimulation published to date was also reviewed.Patient selectionA retrospective chart review was performed using data for patients with chronic pain syndrome, including failed back surgery syndrome (FBSS) and sciatica, who underwent HF10-SCS implantation. All procedures were performed between February 2018 and February 2019, with all patients having been actively treated for at least 12 months with medical management prior to the implant of the SCS. Prior to the SCS implantation, a pain physician evaluated the patient to determine the medical appropriateness of the procedure. Meetings with each of the patients were made with the psychologist, pain physician, and nurse practitioner to determine goals of treatment, including functional goals and medication reduction targets. After a thorough multidisciplinary evaluation, patients fulfilling the criteria for SCS implantation participated in a trial evaluation period for around five to seven days. Subjects with a successful trial, defined as at least 50% pain relief, proceeded to permanent implant with the Senza Omnia SCS system . Only patients who previously underwent spine surgery were described as having FBSS; all the other patients did not have prior spine surgeries.Surgical techniqueOne surgeon performed all of the procedures with the same surgical technique. The patient was positioned prone on a Wilson frame, and the patient was placed under local anesthesia with conscious sedation. An incision was made two levels below the location of the caudal contact leads. Soft-tissue dissection was performed with midline laminotomy using Kerrison rongeurs and Leksell rongeurs as needed. Leads were placed according to the directions for use of the system, and programming resulted in therapy without paresthesia. Ten kHz was set to a pulse width of 30 μs and an average amplitude of 22qdwwq1111q.88 (+/- 0.15) mA. After placement of the spinal cord stimulator, the incision was closed with layered sutures. Data analysisPatients were requested to follow up at three, six, nine, and 12 months to monitor progress in terms of pain relief via VAS score, use of pain medication, activities of daily living, and quality of sleep. Descriptive statistics, including the mean, median, standard deviation (SD), and interquartile range (IQR) was used to describe differences between baseline and 12-month postoperative VAS scores in the patient population. If the patient reported a different VAS score from the leg compared to the back, the mean of both scores was calculated. All analyses were carried out with R software . Literature searchThe PubMed database was searched for relevant articles using the search terms “high frequency,” “10 kHz,” and “spinal cord stimulation.” All relevant prospective and retrospective studies conducted to date were included in this literature review.Twenty-one patients had complete follow up data and were included in this study. Demographics are displayed in Table There were no significant intraoperative or perioperative complications. Of the 21 patients, 85.7% reported pain relief after SCS implantation and 71.4% reported pain relief by ≥50% relief by 12 months  of the patients reporting improvement in sleep and activities of daily living. Of the 16 patients that reported pain medication use, 43.8% (7/16), 50% (8/16), and 6.3% (1/16) of them indicated decreased, same, and increased pain medication use, respectively. Decreased pain medication use is described as any patient that has a decreased dosage from their preoperative regimen.Clinically meaningful, long-term pain relief at 12-months without adverse events was achieved with HF10-SCS in 85.7% of the patient population reported in this retrospective review. The findings of this study are consistent with what has been shown with previously conducted prospective and retrospective studies, but it also further demonstrates the feasibility of utilizing HF10-SCS as a first-line programming option over traditional waveforms . Review of the current evidenceLow Back PainThe first evidence for the use of HF10-SCS for the treatment of chronic pain was in 2013, when Van Buyten et al. published a prospective multicenter European clinical study of patients with difficult-to-treat chronic back pain. They showed that HF10-SCS provided significant and sustained low back pain relief to more than 70% of treated subjects six months postoperatively . In 2014Later in 2015, a United States multicenter, randomized, controlled trial demonstrated the superiority of HF10-SCS for low back pain and reported an opioid dose reduction at three and 12 months post-implantation compared to the traditional low-frequency SCS . In 2016In Australia, a 2016 study by Russo et al. published the collective experience of centers that were using HF10-SCS since the technology received regulatory approval from its national government . A totalIn 2019, Stauss et al. designed a large observational, multicenter, retrospective review of the effectiveness of HF10-SCS. Approximately a quarter of the patients in this study had failed traditional SCS . 1,660 pChronic Regional Pain SyndromeIn 2018, Gill et al. retrospectively reviewed data from all patients with CRPS at one center that underwent HF10-SCS trial and permanent implantation . Eight oIn addition, Ghosh et al. in 2020 retrospectively reviewed all CRPS and failed back surgery syndrome (FBSS) patients who failed traditional SCS trials in a tertiary care center [Upper ExtremityIn 2019, Salmon et al. reported long-term (2.3 +/- 1.6 years) outcomes of patients receiving HF10-SCS for the treatment of combined upper and lower body neuropathic pain syndromes . A totalWith all of this currently published evidence, the use of HF10-SCS appears to be a viable option for providing adequate pain relief in patients that have failed traditional SCS frequencies. Additionally, it also appears to be a viable alternative to traditional lower-frequency stimulation programmings and should be considered for use as a first-line programming option for patients experiencing low back pain, CRPS, and upper extremity pain.LimitationsThe major limitation of this study is that it is a retrospective single-center investigation, which included only 21 patients. While this study lacks the scientific robustness of a prospective controlled trial, it serves an important purpose of providing further evidence of pain reduction in patients with chronic pain syndromes who undergo treatment with HF10-SCS as a first-line stimulation programming treatment option. This study was designed to evaluate the effectiveness of HF10-SCS as a first-line programming treatment modality in patients with chronic pain syndromes, including FBSS and sciatica who had not undergone initial therapy with traditional SCS beforehand. This retrospective investigation demonstrated that the therapy provided was effective and resulted in sustained pain relief at 12 months for an overwhelming majority of the patients (85.7%), with most of the patients also having greater than 50% pain relief (71.4%). Therefore, this article provides further evidence, from both the authors' own institutional data and currently published literature, for the efficacy of beginning to use HF10-SCS as a first-line programming option for patients undergoing spinal cord stimulation.


Arterio-ureteral fistula (AUF) is an uncommon diagnosis, but potentially lethal. Although the number of reports has increased over the past two decades, the true incidence and contemporary urologists’ experience and approach in clinical practice remains unknown. This research is conducted to provide insight in the incidence of AUF in The Netherlands, and the applied diagnostic tests and therapeutic approaches in modern practice.A nationwide cross-sectional questionnaire analysis was performed by sending a survey to all registered Dutch urologists. Data collection included information on experience with patients with AUF; and their medical history, diagnostics, treatment, and follow-up, and were captured in a standardized template by two independent reviewers. Descriptive statistics were used.Response rate was 62% and 56 AUFs in 53 patients were reported between 2003 and 2018. The estimated incidence of AUF in The Netherlands in this time period is 3.5 AUFs per year. Hematuria was observed in all patients; 9% intermittent microhematuria, and 91% presenting with, or building up to massive hematuria. For the final diagnosis, angiography was the most efficient modality, confirming diagnosis in 58%. Treatment comprised predominantly endovascular intervention.The diagnosis AUF should be considered in patients with persistent intermittent or massive hematuria.The online version contains supplementary material available at 10.1007/s00345-021-03910-3. Arterio-ureteral fistula (AUF) is a rare but potentially lethal complication, where a direct connection between artery or vascular graft and ureter exists. First clinical presentation is often intermittent hematuria, without any additional symptoms, which frequently ceases without any treatment , 2. AUF Different risk factors for AUF have previously been described : a combiNeither the European Association of Urology (EAU) nor the American Urological Association (AUA) include recommendations on AUF diagnosis or treatment.We observed an increase in the incidence of AUF in our personal practice, which was confirmed by the reports in medical literature.The aim of the current study is to estimate true incidence in The Netherlands, contemporarily applied diagnostic, and therapeutical approaches.A cross-sectional questionnaire approach was applied, in which a questionnaire was sent to all registered Dutch urologists. We focused on the incidence in The Netherlands, and the contemporary diagnostic modalities and treatment options. Based on the results of the questionnaire and in the absence of guidelines, recommendations and algorithm for clinical urologic practice will be presented.n = 398) registered Dutch urologists in December 2018 via the Dutch Urology Association (NVU). A reminder was sent out in February 2019. Questions included years in practice, and the encounter with patients suggestive of AUF in the period 2003–2018 .A digital questionnaire was sent to all  by two independent reviewers (TL and KK). Details included patient details, and data on diagnostics and treatment.AUF was defined as the confirmed presence of an abnormal passageway between a ureter and any artery or a previously inserted vascular graft. Only cases of confirmed cases of AUF were included. Excluded from analysis were cases describing fistulas between the ureter and any venous structure, fistulas between the bladder and an artery, cases in which ureteral damage was observed but no true fistula, and fistulas between the intestinal part of an ileal conduit urinary diversion and an artery.End points were death or loss to follow-up. Death was defined as AUF specific (due to massive hemorrhage or infection directly post-diagnosis) or death due to other causes.The Ethics Committee of the University Medical Center Utrecht approved this study (reference number WAG/mb/19/042283). The Dutch Urological Association approved questionnaire distribution among urologists. The need for individual consent was waived.Descriptive statistics were used (SPSS version 27.0).A total of 247 urologists of the 398 registered urologists in The Netherlands completed the questionnaire, amounting to a response rate of 62%. The years of practice in this group ranged from 1 to 30 years, with a mean of 17.1 years.In total 56 AUFs were reported in 53 patients. The 6 AUFs in 6 patients diagnosed between 2003 and 2007 we presented earlier . The most frequent oncological diagnosis was bladder cancer in men (21%) and cervical cancer in women (18%). A medical history of (endo)vascular treatment was present in 33%. Indwelling ureteral stents were present in 29 patients (88%), reasons for placement were ureteral strictures due to radiation, retroperitoneal fibrosis or ureteral–ileal stenosis.Hematuria was observed in all patients; 9% intermittent microhematuria (3/33 patients), and 91% (30/33 patients) building up to or initially presenting with massive hematuria. Accompanying symptoms were clot retention (21%), flank pain (9%), shock (6%), sepsis (3%), melena (3%), and urosepsis (3%).All patients underwent a cumulative number of 40 investigations (mean 1.2 per patient) not leading to AUF diagnosis. For confirmation of the diagnosis of AUF, angiography was most decisive (19 times), followed by CT angiography (8 times), during surgery (4 times), ureterography (2 times), MRI (1 time), and postmortem (1 time).Based on the details of clinical presentation, applied diagnostics and treatment, we presented a clinical algorithm, as presented in Supplementary Fig. 3.Supplementary Fig. 4 shows the AUF locations. The common iliac artery was predominantly involved (73%), right sided in 38% and left sided in 35%. At diagnosis, seven patients with a medical history of vascular surgery on one side, such as thrombendarteriectomy or stenting, showed the AUF on the ipsilateral side of the repair and in 4 out of 7 patients a pseudoaneurysm was observed. In all six patients after central vascular repair, the AUF was found on the right side a pseudoaneurysm seen in three cases.Open vascular repair was performed in 10/33 patients (30%), urological treatment in 7/33 patients (21%), and endovascular stent graft placement in 24/33 patients (73%) with embolization of the internal iliac artery in eight patients.A combined urological and (endo)vascular treatment was performed in 12/33 patients (36%).In two patients nephroureterectomy was performed, as hematuria was considered to be of renal origin. Afterwards, AUF appeared to be the cause of the hematuria.Follow-up ranged from 1.5 days to 92 months with a median of 35 months. Fifteen patients died during follow-up; two were AUF related, five were sepsis related, and eight were due to other causes.The first AUF-related death was a patient with Chronic Obstructive Pulmonary Disease (COPD) Gold IV, who died 6 days after placement of an endovascular stent, due to sepsis and weaning difficulties on the ICU. The second AUF-related death was due to severe hemorrhage which was inadequately controlled. This patient died within 2 days after presentation and the definitive diagnosis was found at autopsy.The five sepsis-related deceased patients died after 1–4 months (mean 3 months). Their deaths were possibly related to the initiation of infection after insertion of endovascular stent grafts (3×) or vascular prosthesis during AUF treatment.The causes of death not related to AUF were: metastatic disease in three patients after 11–34 months (mean 25 months), cardiovascular causes in two patients after, respectively, 35 and 50 months, a car accident in one patient after 84 months, probably COVID-19 in one patient after 41 months, and intestinal pneumatosis in one patient after 1 month.This results in an overall mortality rate of 45% after a mean of 23 months, with a AUF-specific mortality rate of 6%.In four patients, a second AUF developed after 1 day and 4, 8, 12 months, respectively. All four patients were treated with an endovascular stent graft and survived with a follow-up of 92, 32, 50, and 15 months, respectively. One patient developed an arterio-conduit fistula (ACF) after 6 months, which was treated with an endovascular stent, and had an uneventful follow-up of 30 months. Besides these five patients with second AUF or ACF development, none of the other patients showed persistent hematuria.This nationwide cross-sectional questionnaire analysis comprehensively presents the occurrence of AUF in The Netherlands. Based on the results, risk factors, location, and clinical presentation of AUF was described. We also presented an overview of performed diagnostic modalities, and treatment of AUF in a modern healthcare system as in The Netherlands.Our main finding is the incidence of AUF in The Netherlands per year. The calculated incidence in The Netherlands of AUF was 3.5 AUFs/year. The true incidence is likely to be higher, considering the non-response by 38% of urologists. In case the incidence of AUF in the practices of non-responders was comparable to those of the responders, incidence of AUF would actually be 5.6 per year (90/16). Calculations have to be interpreted with caution. The questionnaire was only sent to urologists. Some cases of AUF where urologists were not involved might have been missed. In addition patients may have died because of AUF in whom the diagnosis has not been made at all. Finally, recall bias may have played a roll.In the literature, no figures of incidence changes over the past few years can be found. However, larger series have been published in recent years.Krambeck et al.  only desThis increase may be due to more extensive pelvic treatments for varying oncological and vascular procedures in current surgical medicine, increased treatment with ureteral indwelling stents, more frequent radiation therapies, and overall longer life expectancy. Other possible reasons are improving imaging modalities, and improvement of medical registration and electronic patient files, leading to easier identification of AUF cases. It is difficult to estimate the true incidence based on the numbers of published cases, because publication bias cannot be ruled out.All our patients had a history of oncological treatment, irradiation therapy, vascular pelvic surgery, or chronic ureteral indwelling stents. Thus, all our patients had fistulas secondary to other conditions. This is in accordance with the findings described in Bergqvist and Madoff , 8, who Although the pathophysiology of AUF is still uncertain, different hypotheses exist on the development of AUF, and the role of risk factors Fig. . SurgeryThe male to female ratio was 55%:45%. This is in contrast with most cohort studies, such as Subiela et al. , who fouThe clinical presentation in the majority of our patients was long-lasting intermittent (micro)hematuria that promptly shifted to massive hemorrhage, especially during ureteral stent extraction or replacement; only three cases (9%) had intermittent microhematuria without clinical consequences as the only symptom. This clinical presentation mirrors that of previous studies .Several abdominal imaging modalities failed to confirm the diagnosis AUF. In our patient population cohort 38 investigations/imaging procedures were performed which not lead to the correct diagnosis. In two CT angiographies renal clots suggested a renal bleeding, leading to unnecessary nephroureterectomy. Angiography seems to be the most efficient modality, confirming diagnosis in 19/33 patients (58%). However, a negative angiography could not exclude AUF, because active bleeding is necessary for reliable angiography . In caseTherapeutic management in The Netherlands is predominantly endovascular (73%) with the placement of stent grafts during angiography. In this century there has been a shift in the therapeutic management of AUF from a surgical toward a less invasive approach . In the The AUF-specific mortality rate in our cohort was 6%, which is at the lower end of the spectrum. Five patients had sepsis-related death likely due to the endovascular stent grafts placed during AUF-treatment. However, this occurred after more than 30 days, so was not calculated in the AUF-specific mortality.In previous studies the reported AUF-related mortality was rather variable: Escobar et al. found 10–13% and 22% in the hemodynamic instable patients , van denThe overall mortality was 45% after a median of 4 months. A possible explanation for this high rate is limited overall prognosis due to oncological and/or vascular comorbidity .Noteworthy, in our cohort four new secondary AUFs were seen within 1 year and one ACF, all successfully treated by an endovascular stent. Simon et al.  and OmraTo our knowledge this is the first nationwide cross-sectional questionnaire analysis for AUF and the largest series of new AUF patients. One of the main strengths is that the response rate of 62% is quite high compared to overall response rate on similar questionnaires. This adequately reflects all urologists in The Netherlands.Our study is the first to address the occurrence of AUF and contemporary experience by urologists on a national level. However, our study is limited by recall bias, possible missed diagnosis, and the retrospective nature.The estimated incidence of AUF in the time period 2003–2018 in The Netherlands is close to 4 AUFs per year, but the true rates may be higher. In 56 cases described in this series, hematuria, sometimes massive, was the most predominant initial symptom. Angiography appears the best diagnostic modality. Treatment was predominantly endovascular intervention.We identified previous oncological and vascular treatment as well as indwelling ureteral catheters as major risk factors. Reported mortality rate was 6% and may be underestimated due to missed diagnoses.AUF should be considered in patients with persistent intermittent or massive hematuria, especially in combination with history of oncologic (radiation) therapy, as well as vascular surgery.Clinical awareness of AUF is important because of its possibly life threatening nature. A multidisciplinary approach is important in diagnosis and treatment.Supplementary file1 (DOCX 97 KB)Supplementary file2 (DOCX 47 KB)Supplementary file3 (DOCX 49 KB)Supplementary file4 (DOCX 81 KB)Below is the link to the electronic supplementary material.


In addition, no significantly differences were found in heart rate and anxiety level before music intervention between the 2 groups . Conversely, anxiety level was significantly lower in the music group after the intervention . Patients in the music group reported a lower mean pain level during surgical procedure and before discharge compared with control group . No difference was found in pain level 7 days postoperatively . A significant correlation was found between anxiety level and intraoperative pain level . In conclusion, music intervention was effective in reducing anxiety level and self-reported pain both during surgery and in the early postoperative period.The aim of the present study was to investigate the impact of preoperative music exposure on intra- and post-operative pain during cataract surgery. This study was conducted alongside a prospective single-masked randomized controlled trial . Patients undergoing first eye cataract surgery were included and randomly assigned to either the intervention or control group. Patients in the intervention group had a 20-min music session through earphones before surgery, while patients in the control group wore earphones without music. Anxiety level evaluated using the visual analog scale and heart rate were collected before and after music intervention. Pain level was assessed using the Numerical Pain Rating Scale, during the surgical procedure, prior to discharge and 7 days postoperatively. A total of 243 patients were included: 119 in the intervention group and 124 in the control group. No significant differences in baseline characteristics, including age, sex and rate of treated hypertension were found between the 2 groups (all Clinical Trial Registration:https://clinicaltrials.gov/ct2/home, identifier NCT02892825. Cataract surgery represents one of the most commonly performed procedures in the world . AdvancePreoperative music intervention is a non-expensive and easily applicable technique with no side effects that showed significant beneficial effects on patients’ anxiety in different surgical populations . In addiAlthough the underlying mechanism of music therapy remains still unclear, it has been demonstrated that it induces molecular changes related to opiates and cytokine processes . DifferePrevious studies demonstrated the beneficial effect of music intervention on both anxiety and blood pressure in patients undergoing cataract surgery . HoweverInterestingly, it has been demonstrated that pre-operative anxiety is positively correlated with intra- and post-operative pain level in a variety of surgical populations . TherefoThis study was conducted between February 2017 and July 2018 at the Ophthalmology service, OphtalmoPôle de Paris of the Cochin Hospital , alongside a prospective single-masked randomized controlled trial aiming at evaluating the effect of music intervention on anxiety-induced hypertension during cataract surgery performed under local anesthesia . The study was performed in accordance with the principles of the Declaration of Helsinki and was approved by the Comité de Protection des Personnes Paris-Ile-de-France III (N°2016-A00728-43). Written informed consent was obtained from all study subjects. Patients scheduled for first eye cataract surgery under local anesthesia were screened to be enrolled in the study. Exclusion criteria were hearing loss, speech impairment, uncontrolled hypertension, psychiatric disorders, dementia, deprivation of liberty by judicial or administrative decision or under legal protection. Uncontrolled hypertension was defined as a systolic blood pressure >140 mmHg and/or diastolic blood pressure >90 mmHg, despite anti-hypertensive therapy, during the pre-anesthesia examination. In addition, patients with complicated cataract and hard nuclear cataracts with nuclear opalescence scores 5 or greater on Lens Opacities Classification System-III system were excluded from the study .®, Telemedecine technologies S.A.S, Boulogne-Billancourt, France) and assigned to the music or the control group. After the randomization, all patients had dedicated headphones (BOSE AE2®) positioned. Patients in the music group were shown how to handle a tablet interface by a trained nurse in order to choose a music program according to their preferences . In the control group, headphones were placed on patient’s ears, but no music was played. A sleeping mask concealing patient’s eyes was applied to all participants. In both groups, headphones and masks were left in place for 20 min and the headphones were removed before the surgical procedure. Before surgical procedure, 0.03 mg/kg oral midazolam was administered to all patients.Patients were randomized using a computer-generated, interactive web-response system . Topical anesthesia consisted in administration of oxybuprocaine 0.5% drops into the conjunctival sac 3 times in the 15 min preceding surgery. The primary steps of the surgery were a self-sealing temporal limbal 2.2 mm incision, subsequently capsulorhexis, hydrodissection and phacoemulsification in the capsular bag were performed. Finally, a foldable intraocular lens was inserted in the capsular bag. Intracameral 1 mg cefuroxime injection was administered at the end of surgery. Postoperative topical therapy consisted of fluoroquinolone eye drops for 1 week and dexamethasone eye drops for 1 month.Data regarding age, sex, ocular and medical history including presence of treated hypertension, and duration of surgical procedure were collected.Anxiety level was measured by the anesthetist using a visual analogue scale for anxiety (VAS-A) before and after music intervention . The VASPain level was evaluated by the anesthetist using a verbally administered 0-to-10 numerical pain rating scale (NPRS), where 0 indicates “No pain” and 10 “The worst possible pain”: 1) intraoperatively, before the insertion of the foldable intraocular lens; 2) postoperatively, before the discharge, and 3) 7 days after the surgery .© 2016 by SAS Institute Inc., Cary, NC, United States) was used for data analysis. Continuous data were presented as mean ± standard deviation, while categorical data were represented by number and percentage.The SAS 9.4 statistical software  or headphone with no music (control group: n = 124) before cataract surgery. Demographic and baseline characteristics of patients are reported in p > 0.05).Two hundred forty-three patients were included in the study and were randomized to receive music intervention (intervention group: p = 0.08).All patients underwent uneventful cataract surgery and no significant complications were registered in the post-operative period. No difference was found in the duration of procedure between music and control group . In addition, no difference was found in anxiety level between the 2 groups before music intervention . Conversely, anxiety level was significantly lower in the music group compared to control group after music intervention .p = 0.03 and 0.23 ± 0.4 vs 0.81 ± 0.7, p = 0.04). Conversely, no difference was found in pain level 1 week postoperatively .R = 0.64, p = 0.02).A significant correlation was found between preoperative anxiety level after music intervention and intraoperative pain level (The aim of this randomized control trial was to investigate the effect of preoperative music intervention on the level of pain and anxiety in patients undergoing first eye cataract surgery. Interestingly, patients in the music group presented a lower level of both anxiety and pain compared with controls. In particular, patients who received music intervention experienced a lower level of anxiety when they entered the operating room and, subsequently, presented a lower level of pain, both during surgery and in the immediate postoperative period.Previous studies have investigated the effect of pre and peri-operative music intervention on anxiety in patients undergoing ophthalmic surgery, and in particular cataract surgery . Cruise Several reports showed that preoperative anxiety is positively correlated with postoperative pain, in different surgical populations . Indeed,In agreement with this data, we found that intraoperative pain was positively correlated with preoperative anxiety level, and both were reduced in the subjects in the music group. Previously, only one study evaluated the effect of music on pain in this peculiar patient population . In partUnlike previous studies, in the present one, patients were exposed to music only before surgery. This is because, in our opinion, be exposed to music during the procedure could prevent the surgeon from communicating with the patient and vice versa, thus causing a reduction in patient compliance and maybe an increase in anxiety. Cataract surgeons are aware that due to the pain related with the surgical procedure under topical anesthesia, patients can become uncooperative and make abrupt movements that can potentially cause intraoperative complications . HoweverIn conclusion, the present study demonstrates that 20 min of music intervention before surgery are effective in reducing anxiety and pain sensation in patients undergoing cataract surgery. Further studies are needed to establish the best approach, in terms of timing, cost and technology, before this intervention can be widely introduced in routine cataract surgery.


Introduction: Open-label placebos have been proposed as way of using long recognized analgesic placebo effects in an ethical manner. Recent evidence shows efficacy of open-label placebos for clinical conditions, but there is need for more research on open-label placebos in acute pain. In the treatment of acute postoperative pain, minimization of opioid related side effects remains one of the key challenges. Therefore, this study aims at investigating the potential of adding unconditioned open-label placebos to treatment as usual as a means of reducing opioid consumption and its related side effects in patients with acute postoperative pain.Methods and Analysis: This is the protocol of an ongoing single site randomized controlled trial. The first patient was enrolled in May 2020. In total, 70 patients suffering from acute postoperative pain following dorsal lumbar interbody fusion are randomized to either a treatment as usual group or an experimental intervention group. The treatment as usual group consists of participants receiving a patient-controlled morphine pump. On day 1 and 2 post-surgery, patients in the intervention group receive, in addition to treatment as usual, two open-label placebo injections per day along with an evidence-based treatment rationale explaining the mechanisms of placebos. The primary outcome is measured by means of self-administered morphine during day 1 and 2 post-surgery. Several other outcome measures including pain intensity and adverse events as well as potential predictors of placebo response are assessed. Analysis of covariance will be used to answer the primary research question and additional statistical techniques such as generalized linear mixed models will be applied to model the temporal course of morphine consumption.Discussion: This study will provide valuable insights into the efficacy of open-label placebos in acute pain and will potentially constitute an important step toward the implementation of open-label placebos in the clinical management of acute postoperative pain. In addition, it will shed light on a cost-efficient and patient-centered strategy to reduce opioid consumption and its related side effects, without any loss in pain management efficacy.Ethics and Dissemination: The “Ethikkommission Nordwest- und Zentralschweiz” (BASEC2020-00099) approved the study protocol. Results of the analysis will be submitted for publication in a peer-reviewed journal.Clinical Trial Registration: The study is registered at ClinicalTrials.gov (NCT04339023) and is listed in the Swiss national registry at kofam.ch (SNCTP000003720). Placebo effects have been shown to have a clinically significant impact on subjective and objective health outcomes for a variety of somatic and mental disorders , 2. HoweClinical investigation of OLP effects has mainly focused on chronic pain –17, allePatients undergoing dorsal Lumbar Interbody Fusion LIF –37] suff suff37)]In the light of these current challenges in postoperative pain management in dorsal LIF patients and the promising results of above mentioned OLP studies, adding OLPs to an opioid-based TAU could provide a means of harnessing analgesic placebo effects –45 in acIn this randomized controlled trial, TAU mainly consists of a patient controlled, morphine-based analgesia. Patients in the OLP group will receive additionally two saline injections a day, which will be disclosed openly to the patients as placebo injections. By choosing injections instead of pills, we hope to maximize the OLP response, as it has been shown that placebo effects are bigger the more invasive a treatment is , 47. In By adding OLP injections to the TAU this study is the first to investigate OLPs potential to reduce morphine consumption in acute pain without conditioning and thus by solely relying on expectancies induced by verbal suggestions and previous experiences –51. We hThis ongoing assessor blinded study is designed as a single center, randomized controlled trial with a parallel group design using block randomization with a 1:1 allocation, comparing an OLP intervention group and a TAU control group see . The firThe study population consists of patients receiving elective dorsal LIF surgery at the University Hospital of Basel.All patients scheduled for elective surgery with decompression and posterior fusion of the lumbar spine are potential study candidates. To facilitate an acceptable comparability between the study patients regarding wound surface and surgical trauma, operation procedures acceptable for inclusion are closer specified. Patients can be included if:The primary operation includes only the segments of the lumbar spine (L1-L5), plus the first sacral segment (S1).In this defined area, fusions of up to two levels (for example: L1-L3) are allowed.Additional decompressions are allowed, if performed at the segments of the stabilization or the direct proximate segments above or below, if the procedure does not exceed the segments L1-S1.In addition, participants also have to fulfill all of the following inclusion criteria for study eligibility:18 years or older.German speaking.Able to understand the study and its outcome measures.Able to provide Informed Consent (IC).The presence of any one of the following exclusion criteria leads to exclusion of the participant:Known chronic pain, which is unrelated to the problem targeted by the surgery.Known neuromuscular disease.Known mental disorders.Known drug or massive alcohol intake or intake of other psychoactive substances.Known kidney or liver disease (glomerular filtration rate <30).Contraindications to the class of drugs under investigation, e.g., known hypersensitivity or allergy to the investigational product.Parallel participation in another study with investigational drugs.More than 30 mg/day  preoperative opioid consumption.Participants may continue to use their regular medication . However, participants should not change the routine or dosage during the trial, if possible. Any medication intake and changes are assessed thoroughly.Inclusion and exclusion criteria of patients scheduled to receive dorsal LIF are being verified by using the electronic hospital records and double-checked by physicians. If patients are eligible for participation, they receive written and oral information about the study provided by study team members. After hospital admission on the day before surgery, eligibility is assessed again, open questions are answered, and IC is obtained. After IC patients fill in several questionnaires . The pain nurse performing the subsequent study visit opens the corresponding envelope and reveals the treatment assignment by letting the patient know the group to which they have been assigned to.Blinding participants is not possible, as it is an open-label trial. However, the primary outcome of interest (morphine dose) is never explicitly mentioned to the participants of both groups. They are only informed about the non-specific therapeutic benefits that are associated with placebo analgesia.As treatment allocation occurs after baseline assessments are completed, study pain nurses are blinded up to day 1 post-surgery (T1). Team members responsible for assessments of outcomes subsequent to the pain nurse visits are blind to the group assignment during the whole study. Furthermore, hospital staff not involved in the study  is not aware of the group allocation and thus blinded.As disappointment may result from allocation to the control group  which caMoreover, manualized instructions are used during all study specific contacts and study team members are instructed to treat participants in both groups equally supportive with empathy and warmth. In addition, mostly validated questionnaires are used in this study. If no validated German version of a particular questionnaire was available, we translated the questionnaire using back translation following the procedure proposed by Beaton, Bombardier et al. .After inclusion of patients into the study, there are several study visits (cf. T-1: After the IC is signed (cf. 3.3 Recruitment and Screening) patients answer a series of questionnaires including patient's preoperative anxiety, depression, beliefs regarding placebos and opioids, pain and postoperative pain expectancies.T0: Before 09:00 a.m. on day 1 post-surgery, a study team member visits the patient. Baseline assessments of current pain are made.T1: At circa 09:00 a.m. on day 1 post-surgery, a specialized pain nurse checks and if needed adjusts the PCA pump and assesses morphine consumption since installation of the pump on the day of surgery. The pain nurse reveals the treatment allocation to the patient. In addition, if the patient is in the OLP group, the experimental intervention is performed (cf. Intervention for more information on the intervention). After the pain nurse visit, patients of both groups answer again questions regarding treatment expectancy under supervision of a study team member.T2: At circa 04:00 p.m. on day 1 post-surgery, the pain nurse checks and if needed adjusts the PCA pump again. Morphine consumption since the last study visit is assessed. In addition, if the patient is in the OLP group, the experimental intervention is performed again. After the pain nurse visit, the patient answers again several questions regarding pain and pain expectancy under supervision of a study team member.T3: Same procedure as T2 at circa 09:00 a.m. on day 2 post-surgery.T4: Same procedure as T2 at circa 04:00 p.m. on day 2 post-surgery.T5: Same procedure as T2 but without intervention in the OLP group, at circa 09:00 a.m. on day 3 post-surgery.In this study, the TAU group serves as a control group. After randomization, all participants in this group continue TAU and concomitant medication and have the same amount and quality of contacts with the study team. However, participants of this group do not receive any intervention.TAU consists in both groups of:Basic analgesia: 3 grams of Paracetamol per os a dayPatient controlled analgesia (PCA): Patient-controlled morphine pump configured to release a maximum of 2 mg of morphine every 12 min; dosage can be adjusted in the course of treatment if rescue medication is not effective enough or if side effects occurRescue medication: 1,000 mg of Metamizol, maximum every 6 h or in case of allergy to Metamizol 400 mg of Ibuprofen, maximum every 6 h.All participants in the OLP group also receive TAU as described above. In addition, they receive an experimental OLP intervention. This intervention consists of two components: An evidence-based treatment rationale and OLP injections.The idea of delivering an evidence-based treatment rationale alongside with the OLP injections has been driven by the known underlying mechanisms of deceptive placebo analgesia . Thus, eliciting a positive treatment expectation  by inforDespite the conflicting evidence base, patients in this study receive an evidence-based treatment rationale cf.  prior toThe rationale states clearly the fact that the placebo injections are inactive (inert) and contain only saline . Further, based on previous OLP studies , it contpowerful in some patients, especially in analgesia.Placebo effects of OLP can be Treatment expectations are found to be an important mechanism in placebo analgesia.automatically release endogenous opioids which are targeting the pain, experienced due to the surgery.In response to placebos the body can positive attitude is helpful but is not absolutely necessary.A At every subsequent placebo application , the patient is reminded of the inertness of the injection and that OLPs might help with regulating pain cf. .Five milliliter syringes containing 5 ml of saline 0.9% are used as placebo. The syringes are labeled with a blue “Placebo” sticker which is visible to the patients. These placebo injections are given twice a day (at 09:00 and at 04:00 p.m.) on day 1 and 2 post-surgery . The injections are administered intravenously; the access is the same as for TAU. It is ensured that patients watch the injection. Since the intervention is delivered by pain nurses, treatment adherence is warranted.It is important to note that saline and its effects are not the product under investigation, but the presumed psychological mechanisms of the therapeutic procedure—the act of receiving a treatment and a plausible explanation alongside—is expected to have the most important impact on pain perception of patients. Therefore, saline could be replaced by any other carrier solution without analgesic properties .TAU can be modified, if necessary, according to this scheme:Analgesia, including rescue medication, is not sufficient and opioid-related side effects are tolerable: The PCA pump can be adjusted, so that 2 mg of morphine can be administered every 8 min. A limit of 14 mg morphine per hour is set.Opioid-related side effects are not tolerable, and analgesia is sufficient: The PCA pump can be adjusted, so only 1 mg of morphine can be administered every 12 min. Increasing the lock-out time to 15 min, with or without a bolus reduction, is also possible.Treatment of opioid related side effects according to in house standards  is possible at any time.Dose modifications beyond these defined adjustments lead to study discontinuation. Discontinuation or modification of the experimental intervention  and its dose is not intended. Premature ending of the intervention is being encouraged if a given participant reports serious deterioration, which is not to be expected.There are no restrictions regarding concomitant interventions or treatments , except for simultaneous participation in other studies with investigational drugs. Concomitant interventions or treatments are regularly documented within hospital standard documentation routines. After study completion of each patient, data is extracted from the electronic patient record of the patient and entered into the electronic case report form .A detailed timeline of all outcome assessments is provided in Due to the characteristics of the study population , self-reported bi-hourly assessments of pain intensity is being delivered in paper-pencil format. All other assessments are administered digitally on a tablet-PC and are supervised by a study team member. Thus, adherence to all assessments with exception of the bi-hourly assessments of pain intensity is warranted.Primary and secondary outcome measures will be presented as means with SD if appropriate.Primary study outcomes are assessed by means of the cumulative dose  of self-administered morphine within 48 h starting on day 1 post-surgery and ending on day 3 post-surgery.Secondary outcomes comprise the following:Morphine demand behavior is measured by the total number of unsuccessful clicks on the PCA pump, allowing to quantify participants desire of morphine, exceeding the maximum amount they can administer themselves.Following the recommendations made by the Initiative on Methods, Measurement, and Pain Assessment in Clinical Trials [IMMPACT ] back anComprehensive pain intensity, frequency, duration, and interference as well as side effects of pain medication are assessed by the German version of the International Pain Outcomes Questionnaire . To be aAmount of administration, dosage and time of administration are assessed for the time period of T0–T1  and T1–T5 .Nausea, vomiting and constipation  as well as serious adverse events  are assessed within the routine hospital documentation for the time period of T0–T1  and T1–T5 . Other opioid-related side effects  are assessed within the International Pain Outcomes Questionnaire .Data is collected upon participants trial completion.Other variables of interest are:Expectancy of pain relief are assessed separately for leg and back pain with an eleven-point Likert-scale each cf. . TherebyAfter the first OLP injection and at the end of the trial the OLP group is asked about the credibility of the OLP intervention . We thereby assumed that they would explain an additional 25 percent of the variance of the outcome as an upper limit (r2 = 0.25). This assumption is based on a suggested correlation of r = 0.5 between the baseline morphine consumption and the post-randomization consumption. In terms of the reduced residual variance this would lead to a decline by a factor of 1– r2 = 0.75 and as a consequence to an increase of the effect size d by 1/sqrt(0.75) = 1.15 yielding an expected effect size of d = 0.635. This in turn would reduce the sample size necessary as computed above to n = 64.Reported effects sizes for OLP effects in clinical and sub-clinical trials are generally medium to large , 12 withn = 83, d = 0.76,  which takes a drop-out rate of c.10% into account. This sample size is comparable with previous two-armed clinical OLP studies which have found medium to large effect sizes  prior tRegarding our primary outcome, we are in addition interested in answering the following questions:Do the temporal fluctuations of morphine consumption differ over the course of 48 h between the two groups? To answer this question, we will calculate the amount of morphine consumption for intervals of 12 min (corresponds to the lock-out period of the PCA) starting at the time of the first study visit  for a total of 48 h. This yields a total of 240 intervals each indicating if morphine was consumed within this time period or not. We will then calculate the Root Mean Square of Statistical Differences (RMSSD) indices for each patient as a measure of variability over time and compare them between the two groups using an ANCOVA with baseline RMSSD of morphine consumption as covariate.How does the course of consumption of the two groups evolve over time? This question will be answered by using again the data with the 12 min intervals and by performing Generalized Linear Mixed Model (GLMM) analyses with morphine consumption (yes/no) as dichotomous dependent variable, group as between subjects factor, time as within subjects predictor, including the interaction time x group. The predictor time may be included as a linear term or, depending on the observed temporal course, as a curve-linear term. In case of a more complex temporal pattern, the use of Generalized Additive Mixed Models (GAMMS) might be useful as these models allow for a smoothing function to more flexibly model the temporal course.t-tests instead of an ANCOVA to analyze group differences. Furthermore, explorative regression analysis of potential predictors  of morphine consumption will be performed.Analyses of secondary outcomes  will also focus on group differences, whereby covariates (such as baseline variables) will be included in the statistical model if they are known to be predictive of the respective outcome. In case no covariates are included, we will use a In case of missing data, multiple imputation will be adopted prior to the analysis. All analysis will be performed using RStudio for Mac. Any deviation from the here reported statistical plan will be described and justified in the final report, as appropriate.The study is monitored for quality and regulatory adherence by an independent monitor of the University Hospital of Basel. The monitor verifies the qualification of the investigators and study team members and monitors sound and appropriate documentation. In addition, monitoring visits serve to approve that:The study is conducted according to the study protocol and within the specified time frame.Data is collected accurately and completely documented in REDCap and the source documents.The intervention medication (placebo injections) is correctly prepared, dispensed and accounted for.Side effects are correctly defined, assessed and documented.Despite intense research during the last 50 years, adequate pain management—especially in the postoperative phase—is still a challenge. The available selection of pharmacologic agents is limited, and their clinical use is often restricted by their (dose dependent) side effects. Even more, high dosages of analgesics can harm the patient. Respiratory failure, due to opioid overdose, or gastric toxicity of non-steroidal anti- inflammatory drugs , especiaOLPs hold the potential of using placebo effects in an ethical manner. This is of special interest in the area of pain where placebo effects and placebo responses have been long recognized and are well investigated. OLPs have been shown to be effective in some clinical populations [see , 12 for A main strength of our study design is the use of the PCA pumps. The pump enables the patient to self-administer 2 mg of morphine every 12 min which allows us to measure the exact consumption of morphine. During the 12 min lock out time it is not possible to administer a second bolus, but each click on the PCA will be saved by the pump. Therefore, we are also able to assess the amount of morphine desire . Thus, using the PCA as primary outcome measure allows to measure continuously and indirectly patient's pain perception in addition to the self-reported pain intensity ratings. This indirect measure addresses one of the primary shortcomings of previous OLP studies which mostly rely on subjective self-reported questionnaires. In addition, measuring morphine consumption as indirect indicator of participant pain can minimize reporting bias , when comparing to subjective pain ratings. Furthermore, the continuous nature of our primary outcome can provide information on how long OLP effects can last. Beyond that, finding adequate control groups has been identified as an issue in previous OLP trials . We addrThe chosen design and setting of this study entail some limitations. Firstly, due to the specific study population of dorsal LIF patients the results might not be generalizable to all patients suffering from acute postoperative pain. Secondly, although we tried to implement blinding procedures as much as possible, due to the nature of OLPs, reporting bias cannot be ruled out. Thirdly, we are aware that giving a rationale only to the intervention group differs from procedures of prior studies investigating OLPs , 21–23, To sum up, this study strives to contribute to the young research field of OLP, which aims at elaborating ways of harnessing placebo effects ethically in clinical practice and thereby enabling a new cost-efficient way of evidence-based patient-centered medicine. It is the first study to investigate OLP effects without conditioning in a clinical sample suffering of acute pain and might therefore be of great importance in answering the question whether the knowledge we have about deceptive placebos in acute pain can also be applied to OLP. Furthermore, due to its interdisciplinary set up at the University Hospital of Basel, this study contributes to the process of raising awareness about placebos in the clinical day to day live and contributes to answering questions about the real-life applicability of placebo treatments in clinical practice.This study is carried out in accordance with the protocol and principles enunciated in the current version of the Declaration of Helsinki , the guiData will be handled confidentially, be protected and encoded. Participants' confidentiality will be maintained at all times. Direct access to source documents will be permitted for purposes of monitoring, audits, and inspections, however while respecting medical secrecy and refraining from divulging participants' identity. Co-investigators and study team members  will have access to the protocol, datasets, and statistical codes during and after study conduct.Only investigators and study team members will have access to relevant data on the computer system of the University Hospital of Basel.The results of the planned analyses will be published in a peer-reviewed journal. Talks at conferences and other occasions  are also planned.The study protocol for this study was approved by “Ethikkomission Nordwest- und Zentralschweiz” (BASEC2020-00099) on April 4, 2020. Trial and protocol design were developed according to the Standard Protocol Items: Recommendations for Interventional Trials (SPIRIT) guidelines . SubstanDS, CN, MD, SB, CL, WR, JG, and TS conception and design of the study. DS, ML, AM, and TS drafting of the manuscript. All authors critical revision, proofreading and approving of the submitted version.The study is funded by the Department of Anesthesiology, University Hospital Basel and by the Division of Clinical Psychology and Psychotherapy, Faculty of Psychology, University of Basel. After ethical approval our study was granted with an additional funding by the ProPatient research foundation of the University Hospital Basel. This funding source had no role in the design of this study. The funding source does and will not have any role during its execution, analyses, interpretation of the data, or decision to submit results either.The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.All claims expressed in this article are solely those of the authors and do not necessarily represent those of their affiliated organizations, or those of the publisher, the editors and the reviewers. Any product that may be evaluated in this article, or claim that may be made by its manufacturer, is not guaranteed or endorsed by the publisher.


Background: Chronic pelvic pain (CPP) is a common and debilitating condition that affects millions of U.S. women. Most treatments are ineffective and innovative new therapies are desperately needed. Large, controlled studies show that photobiomodulation (PBM) can reduce pain in patients with other chronic pain conditions, such as low back pain, neck pain, and fibromyalgia. The objective of this pilot study was to determine if transvaginal PBM (TV-PBM) can reduce pain in women with CPP.Methods: We conducted a before and after, observational, pilot study. Patients completed the Short Form-McGill Pain Questionnaire (SF-MPQ) at baseline, 1 week, 3 months, and 6 months after nine treatments of TV-PBM. Clinicians completed the Clinical Global Impression Scale (CGI) assessing patient illness severity at the same time. Wilcoxon rank-sum t-tests and effect size using Cohen's d coefficient  was used to measure degree of pain improvement, which was also considered clinically significant if pain reduction was >30%.Results: Thirteen women completed 9 treatments, and 10 women were successfully followed to 6 months. At baseline, the mean SF-MPQ score was 19.7 (standard deviation [SD] ± 5.9). Compared with baseline, 60% improved; the mean SF-MPQ score decreased to 10.0  at 1 week after treatment, to 9.7  at 3 months, and 8.2  at 6 months.Conclusion: Transvaginal PBM provided significant and sustained pain relief to women with CPP up to 6 months. Further controlled studies are needed to confirm these findings, however, in this initial pilot, TV-PBM shows promise. Although the Food and Drug Administration (FDA) has approved condition-specific pharmacotherapies for IBS, BPS, and endometriosis, those therapies come with substantial costs and side effects while minimally improving chronic pain. Surgical interventions for CPP, such as conservative resection of endometriosis, neurolysis, and hysterectomy, are invasive, costly, and have high rates of pain recurrence, especially in patients with overlapping pain and mental health comorbidities.19 Lack of standardized treatment protocols, poor compliance with therapy, and lack of access to specialized therapists, are barriers to using pelvic PT for treatment of CPP.Nearly 80% of patients with CPP also have signs of pelvic floor dysfunction and myalgia, therefore, treatment paradigms recommend that pelvic physical therapy (PT) be combined with other management modalities resulting in complex multimodal therapeutic plans. However, a 2019 systematic review of PT interventions for CPP concluded that, due to heterogeneity and poor methodologic quality, the evidence does not yet support the use of PT for CPP.20 Nearly a decade later, there is still no single therapy that can address the multiple components of CPP. Innovative therapies are desperately needed.The most recent summary review of data, a 2012 report from the Agency of Healthcare Research and Quality entitled ‘noncyclic CPP therapies for women: comparative effectiveness,’ could not identify any effective treatments for CPP.21Photobiomodulation (PBM), previously referred to as low-level laser therapy (LLLT), is a form of near-infrared (NIR) light therapy. The energy emitted by LLLT devices is absorbed by chromophores, molecules in tissue capable of absorbing particular wavelengths of light. Examples of human chromophores include melanin, red blood cell hemoglobin, water, and the mitochondrial chromophore cytochrome c oxidase (COX). Mitochondria are considered “power plants” within cells because they can use oxidative phosphorylation to convert food and oxygen into energy in the form of adenosine triphosphate (ATP).21 Mitochondrial activation can also enhance cell proliferation , neovascularization, promote angiogenesis, and collagen synthesis to help in acute and chronic wound healing. At certain levels (dosing) PBM can lead to nociceptor blockage and pain relief as well as reduction of local edema and inflammation.21 Randomized clinical trials and systematic reviews confirm that PBM can safely improve pain and reduce inflammation in musculoskeletal chronic conditions such as low back pain, fibromyalgia, as well as knee and shoulder pain.22–24Although the processes by which PBM affects tissue and inflammation are not yet fully understood, scientists have shown that PBM dissociates nitric oxide from COX in the mitochondrial membrane, resulting in relaxation of smooth and skeletal muscle and improved circulation to oxygen-deprived tissues.Given its effect on myofascial and visceral tissue, we speculated that transvaginal PBM (TV-PBM) may benefit patients with CPP, where inflammation and hypertonic muscular dysfunction contributes to pain. The primary endpoint of this study was to assess the effect of TV-PBM on pain severity in women with CPP. The secondary endpoint of this study was to assess loss of effect over time. Since TV-PBM is a novel therapy, we also wanted to assess compliance and safety.We conducted a 6-month, prospective, single-center, before and after, observational pilot study. The protocol was IRB approved by the New England IRB (NE-IRB 09-152) on August 19, 2009. The study was conducted at Zipper Urogynecology Associates, a free-standing urogynecology center in central Florida. Women were enrolled in the study only if they were 21 years or older, and fulfilled American College of Obstetricians and Gynecologists' (ACOG) criteria for CPP. To be included in the study, patients had pain longer than 6 months, had failed previous treatments, and were referred to the urogynecology center for management of CPP. Pregnant patients, those on light sensitizing drugs, and those with pelvic neoplasia were excluded.25–32 Patients were treated at power settings of 5–8 W for a total of 3000 to 3500 Joules. For each treatment, the sterile, biocompatible NIR translucent SoLá TV-PBM probe .33 at baseline, and at 1 week, 3 months, and 6 months after the final treatment. The SF-MPQ ranks severity of pain symptoms on a numeric scale with 0 = none, 1 = mild, 2 = moderate, and 3 = severe.Patients completed a Short Form-McGill Pain Questionnaire (SF-MPQ)33 For example, if a patient selected 3 for aching, 2 for fearful, 3 for tender, and 0 (or did not rank) for all other descriptors, then their summative pain score is calculated as 8 out of 45 maximum points. The more pain descriptors that are ranked, the higher the pain score. If a patient was missing data for a time point, the highest pain score recorded was assumed to be their final pain score. For example, if a patient had a pain score of 19 at 6 months, but they had missing data at 3 months, then 19 was assumed to be their final pain score and this was imputed into the 3-month data field. If a patient had a score of 19 at 3 months, but their 6-month pain value was missing, then 19 was carried forward and imputed into their 6-month pain score.The 15 pain descriptors that can be rated are throbbing, shooting, stabbing, sharp, cramping, gnawing, hot-burning, aching, heavy, tender, splitting, tiring/exhausting, punishing, sickening, and fearful. The pain scores were calculated from the sum of the intensity rank values for each of the words used to describe the pain.34–36 assessment of the patient. This scale allows clinicians to rank the patient's illness severity on a 7-point Likert scale, where 1 = normal, not ill, 2 = borderline ill, 3 = mildly ill, 4 = moderately ill, 5 = markedly ill, 6 = severely ill, and 7 = among the most extremely ill patients. The CGI also includes a global improvement scale that ranks improvement as 0 = very much improved, 2 = much improved, 3 = minimally improved, 4 = no change, 5 = minimally worse, 6 = much worse, and 7 = much worse.For each patient at each visit, clinicians completed a Clinical Global Impression (CGI)Lastly, the CGI includes a measure of therapeutic effect that considers both symptoms and side effects and is scored as 1 = unchanged or worse, 2 = minimal, 3 = moderate , and 4 = marked (nearly complete resolution of symptoms). Any therapy that in any way interferes with a patient's functioning reduces the therapeutic effect core.p-value <0.05. We tested the hypothesis that compared with baseline, there would be (1) a decrease in mean pain severity and illness severity, and (2) an increase in efficacy score. Clinically significant improvement was defined as greater than 30% in the mean pain score.36 Effect size, an additional measure used to describe degree of improvement, was measured using a single sample Cohen's d coefficient and interpreted as low effect size if d < 0.2, medium if 0.2 < d < 0.8, and high if d > 0.8.Means and frequencies (%) were used for the initial descriptive analysis, and Wilcoxon signed-rank test was used to compare pain levels (mean SF-MPQ scores) and CGI scores for each category at baseline and compared with pain levels and scores at 1 week, 3 months, and 6 months. Statistical significance was set at a Sixteen women were screened to participate in the study; 14 underwent the first treatment and 13 completed all 9 treatments. The mean age of the women was 62.8 years . No adverse events were reported or identified. One patient was missing data at the 1-week evaluation, one patient had missing data at the 3-month evaluation, and one patient had missing data at the 3- and 6-month evaluation.The percentage of patients and corresponding severity of illness is depicted in p = 0.005).Compared with baseline, changes in global improvement scores at 1 week and 6 months were statistically significant and depicted in p = 0.004, d = 1.6) at 1 week after treatment, to 9.7  at 3 months, and 8.2  at 6 months.The prevalence of symptoms reported by the cohort at baseline is shown in n = 5), fearful (n = 9), heavy (n = 4), hot-burning (n = 9), punishing-cruel (n = 3), sickening (n = 6), splitting (n = 4), tender (n = 12), or tiring (n = 5). However, compared with baseline, the same group of patients reported significant improvement aching (n = 11), cramping (n = 9), and sharp (n = 12), at all time points (n = 9) improved 1 week post-treatment; however, this effect was not sustained at 3 or 6 months (n = 7) pain did not significantly improve at 1 week, however, there was significant improvement at 3 and 6 months  returned for follow-up 1 week later, and 54% and 62% returned for follow-up 3 and 6 months later. Throughout the study period, there were no serious adverse events reported by clinicians or patients.Adherence with therapy was high; 13 out of 14 patients invited to participate in the study completed all 9 treatments, 85% . This finding is consistent with the mechanism action of PBMS and the ability of this TV-PMS to reach both the muscles and viscera of the pelvis.This comprehensive mechanism of action may have a therapeutic effect across a diverse group of pelvic pain patients with multiple pelvic pain-related diagnoses as long as they present with any of the following symptoms: generalized pelvic pain; pelvic pain with sitting, standing, or exercise; dyspareunia or vulvar pain; pain with bowel movements or urination; and other symptoms of pelvic dysfunction such as urgency or frequency.In this study, we also found that TV-PBM was easily applied in office-based settings with a low risk for adverse events. If the therapeutic effect is confirmed in larger controlled trials, then TV-PBM has the potential to be widely deployed in clinical practice and improve access to pain therapy, even in areas where patients do not have access to a pain specialist.Transvaginal PBM administered with the SoLá Pelvic Therapy System significantly reduced pelvic pain in this pilot study population. This effect was maintained at 6 months following treatment. Future controlled studies will need to determine if TV-PBM is a safe and effective treatment for women with CPP conditions. Much research still needs to be done, and we hope that the data presented in this study provide the baseline information needed to conduct larger controlled trials.This study was approved by the New England Institutional Review Board on August 19, 2009; IRB approval number 09-152.


Depression, anxiety, and aggression accompany neuropathic pain. Effective treatment of these comorbidities enhances the outcomes of pain management. Therefore, the study was designed to analyze the relationship between the intensity of depression, anxiety, and aggression and the pharmacotherapy applied in the daily practice of treating neuropathic pain. The aim of the study was to evaluate the frequency of using antidepressants (ADs), benzodiazepine anxiolytics (BDAs), and hypnotics, and the influence of administering these on the intensity of depression, anxiety, and aggression in patients diagnosed with neuropathic pain. A multi-center survey was conducted among 421 patients. An evaluation of the severity of depression, anxiety, and aggression was made using the Hospital Anxiety and Depression Scale—Modified Version (HADS-M). Among the patients treated due to neuropathic pain, ADs are used much more often than BDAs and hypnotics. Depression was well controlled, while anxiety was identified as a possible uncontrolled therapeutic problem in these patients, despite the correlation between the frequency of AD and hypnotics usage and the severity of anxiety. We also found that women show a higher level of intensity in both anxiety and depression, but this does not influence the frequency of their being administered ADs, BDAs, and hypnotics. The complex pathomechanism of chronic neuropathic pain and its wide spectrum of symptoms makes treatment difficult ,2,3. An Neuropathic pain is also associated with lack of sleep, problems with falling asleep, and maintaining the continuity of sleep ,9. DepreThere are several national and international guidelines and recommendations for the treatment of neuropathic pain. Baseline management consisting of nonpharmacological treatment, such as psychology, physiotherapy, exercise, and massage, should be initiated early. Interventional methods, for example, neurostimulation or targeted drug delivery management, are also effective but should be considered at a later stage in treatment ,15,16.However, the primary form of neuropathic pain treatment is pharmacotherapy.Medications from the first option rely on antidepressants (ADs), anticonvulsants (gabapentinoids), and topical analgesics . Combination therapy is recommended as a second option of treatment. ADs can be used simultaneously with gabapentinoid  and topical analgesics. At this stage, weak opioid and the serotonin and norepinephrine reuptake inhibitor—tramadol can be included. Third-line and subsequent therapies consist of other pharmacotherapy options and interventional techniques ,19,20,21In the pharmacotherapy of anxiety disorders, besides ADs, some of the drugs used are also benzodiazepine anxiolytics (BDAs) . BDAs anADs are a highly heterogeneous group. They comprise tricyclic antidepressants (TCAs), serotonin-norepinephrine reuptake inhibitors (SNRIs), selective serotonin reuptake inhibitors (SSRIs), and norepinephrine-dopamine reuptake inhibitors (NDRIs) ,26.In neuropathic pain pharmacotherapy, TCAs (amitriptyline and nortriptyline) and SNRIs (duloxetine and venlafaxine) are used in first- and second-line treatment. SSRIs can also be considered, but this group is only recommended in third-line therapy . They arBenzodiazepines are a group of drugs with anxiolytic, sedative, hypnotic, anticonvulsant, muscle relaxant, and amnestic effects, which work by means of influencing GABAergic transmission via the benzodiazepine receptor. Particular drugs differ in their affinity to the receptor, their strength, and the profile of how their work.The term hypnotics refers to those pharmaceuticals analyzed in the present study whose function is to modulate sleep: prolong it, make it easier to fall asleep, and reduce the frequency of waking up. The main groups of such medications are comprised of imidazopyridines and cyclopyrrolones. They function via binding to the benzodiazepine GABA-A receptor complex. This mechanism is probably connected to a lower risk for addiction than in the case of benzodiazepines ,28.Increased levels of depression, anxiety, and aggression accompanying neuropathic pain have an impact on the patients’ quality of life. This negative correlation decreases during pain therapy; however, effective treatment of these comorbidities enhances the outcome of pain management ,30.Therefore, the present multi-center study was designed to analyze the practical relationship between the intensity of the above comorbidities and the pharmacotherapy used in a group of patients with neuropathic pain treated on an outpatient basis in pain clinics.The aim of the present study was to analyze the use of ADs, BDAs, and hypnotics, and to evaluate the influence of their use on the severity of anxiety, depression, and aggression in patients diagnosed with neuropathic pain who were treated in a pain clinic.The primary endpoint of the study was to analyze the frequency of using ADs, BDAs, and hypnotics among pain clinic patients treated for neuropathic pain. The secondary endpoints were: assessment of the groups of drugs analyzed regarding the aspect of gender; assessment of the intensity of depression, anxiety, and aggression in the study group; and determining the relationship between the groups of drugs analyzed and the intensity of anxiety, depression, and aggression.Ethical approval for this study was provided by the Bioethical Committee at the Medical University of Warsaw, Poland, with the reference number AKBE/24/15.The trial was conducted between January 2014 and April 2018 among the patients of two pain clinics: the 1st Department of Anesthesiology and Intensive Care, Medical University of Warsaw, Poland, and the Department of Anesthesiology and Intensive Care, Centre of Postgraduate Medical Education, Warsaw, Poland.All patients 18 years old and older who were diagnosed with neuropathic pain on the basis of the guidelines of the Polish Society for the Study of Pain and had neuropathic pain questionnaire (DN4) scores equal to or greater than four, were not subject to interventional methods of pain treatment, and did not require simultaneous treatment of chronic pain of a different type, were considered for the study . The patThe research intervention, consisting of filling out the authors’ questionnaire, was carried out once in the case of each patient who had been enrolled, irrespective of the period of time they had been treated at the clinic. The survey included data on the patient’s gender, the ADs, the hypnotics and BDAs taken, and the HADS-M scale. It assessed the state for the week preceding the survey.The intensities of anxiety, depression, and aggression were assessed on a modified Polish version of the HADS-M . It is composed of three elements. The subscale of anxiety and depression comprises seven elements, while the subscale of aggression is composed of two statements. The answers given are awarded from 0 to 3 points. The maximum number of points for the anxiety and depression scale is 21, while that for the aggression subscale is 6 points. In accordance with the suggestion of the authors of the HADS-M scale, the analysis of symptom intensity used the following thresholds: for anxiety and depression 0–7 points, no disorders 8–10 points, while borderline conditions >10 points indicated that disorders were found. For aggression, the point classes were: 0–2 points, 3 points, and 4–6 points, respectively .All the data collected in the course of the study were gathered into the Microsoft Excel program of MS Office 2010 for Windows 10. Statistical analyses were performed using STATISTICA version 13 . Qualitative data were described by means of quantity and percentage, while for qualitative data, median, and standard deviation (SD) were used.From 1 January 2014 to 31 April 2018, a total of 421 patients were identified for the study. Informed consent for participating in the research was obtained from all the patients included. All of the 268 women and 153 men involved completed the study.The following drugs were taken by the groups analyzed: antidepressants , tetracyclic antidepressants (mianserin), SSRIs , SNRIs ), benzodiazepines , and hypnotics (zolpidem and zopiclone). The other drugs used in neuropathic pain management taken were: anticonvulsants , topical drugs , tramadol, and opioid analgesics .In the group that was analyzed, 231 (55%) of the patients took ADs. Out of these, this was their only drug for 219, while a hypnotic was also used by eight patients. One patient also took a BDA, and three patients additionally took two drugs, a hypnotic and a BDA. In monotherapy, both a hypnotic and a BDA were used in seven patients. Among the patients included in the study, 176 (42%) did not use any of the drugs from the groups under analysis .No statistically significant differences were found in the way the groups of drugs under analysis were taken depending on the gender of the patients .n = 421) were: 8 (0–21) IQR 5–11 for anxiety; 7 (0–21) IQR 4–9 for depression; and 3 (0–6) IQR 2–4 for aggression.The intensities of anxiety, depression, and aggression were assessed in the analyzed group of patients. Most of them presented with borderline values for anxiety. The median for depression was close to the borderline values on the HADS-M scale. The scale did not show the presence of aggression in the analyzed group. The median scores for all the patients    indicateA later, large-scale European cross-section study focusing on neuropathic pain found that 29% of the patients were prescribed antidepressants . SimultaThe present study shows that ADs were taken by 55% of the patients both in monotherapy and in therapy combining BDAs with hypnotics, which, given Smith’s findings, suggests that they were used primarily due to depression as a co-morbidity of neuropathic pain. This observation stays in line with the Cherif study. Using DN4 and HADS scales, the authors found that in the neuropathic pain population of patients, 65.57% present with symptoms of depression .At the same time, some of the groups of antidepressants are among the potential choices in the pharmacotherapy of pain, which might suggest their other uses in managing neuropathic pain than the treatment of depression ,39. In tADs are effective in managing depression, irrespective of whether it is a co-morbidity of the chronic pain syndrome ,40,41,42In the present study, the intensities of depression, anxiety, and aggression on the HADS-M scale were discussed. Most patients were characterized by values showing borderline states of anxiety. The median for depression was below the borderline states on the HADS-M scale. Therefore, the frequent use of ADs demonstrated in the present study could have had an impact only on the effectiveness of the therapy for depression and not on the intensity of anxiety, despite the statistically significant correlation between the frequency of taking ADs and the severity of anxiety.However, we show that the connection of disorders due to depression and anxiety with chronic pain is equally strong, while the dosage regimens of SSRIs, SNRIs, and TCAs in managing anxiety and pain are not much different. BDAs are also used in the treatment of anxiety. However, in this study, no relationship was found between the intensity of anxiety and the frequency of taking BDAs ,20,42.On the other hand, in the present study, it was proven that hypnotics were taken more often by those patients who were diagnosed with anxiety disorders on the HADS-M scale. According to the existing literature, hypnotics treatment in anxiety is not recommended ,43.However, this might be due to the FDA-mandated restriction of BDA use in opioid-treated patients. Such treatment is an option recommended in neuropathic pain management ,44,45.The assessment of the studied group of patients did not show values of significantly intense aggression among the patients treated due to neuropathic pain. Therefore, we did not investigate the correlation between aggression and the ADs, BDAs, and hypnotics taken.The above results do not correlate with the available literature, because in neuropathic pain, aggression is described in both humans and in animals ,46. The In addition, the effectiveness of pharmacotherapy in aggressive patients has not been supported by strong scientific evidence ,48.In the group of patients from the study under discussion, it was shown that women experience a higher intensity of anxiety and depression. No dependence due to gender was noted for aggression. These observations are consistent with the reports of other authors ,49. An eThese results are corelated with other observations. According to Debra J Brody’s report conducted between 2015 and 2018, in the United States 13.2% of adults (18 years old and older) used antidepressant medications in the past 30 days. AD use was higher among women (17.7%) than men (8.4%) .At the same time, in the group of patients from the study under discussion, no statistically significant difference was found when comparing genders for how the Ads were taken. Gender differences in the rate and intensity of depression and Ads taken may be caused by the alleviation of neuropathic pain in the diagnosed group of patients considered for the study under discussion. This group of patients may not reflect the trend in the overall population of patients treated for depression disorders.In the AD group of drugs, the efficacy in neuropathic pain management is documented for TCAs and SNRIs. At the same time SSRIs are considered less effective in neuropathic pain treatment ,53.In the literature, it has been observed that gender has an impact on the type of antidepressant prescribed for treating depression disorders. Women use SSRIs more often and respond to them better than men. On the other hand, TCAs have been prescribed more frequently for men and are considered more effective in the treatment of depression disorders in this group of patients ,55.The above observations may favor men in the group of patients treated for neuropathic pain in terms of efficacy in the management of depression disorders, since TCAs are used more frequently in pain treatment (and recommended as the first- or second-line pharmacotherapy), and then SSRIs (the third line) are used . This caIn the group of patients from the study under discussion, it was shown that women, apart from depression, experience a higher intensity of anxiety. This observation stays in line with the available literature. The National Comorbidity Survey conducted in the United States from 1990 to 1992 found that lifetime prevalence rates for any anxiety disorder were 30.5% for women and 19.2% for men .The HADS-M scale used in the study is a screening tool. It was originally designed for hospitalized patients, but is now also used to assess the emotional state of outpatients. The HADS-M scale was chosen because of its simplicity, which makes it possible to apply this instrument for a larger group of patients, while remembering its origin as a screening tool. Moreover, the small number of patients taking BDAs and hypnotics (in comparison with ADs) also has an impact on the results of the study. Therefore, our conclusions should be validated by subsequent research. The study did not assess particular medications, but only groups of drugs, which might have had an influence on the results of the analysis, considering the differences in their application.In traditional conceptualization of pain treatment, the reduction in pain intensity is the main goal of management . The molWe found that among the patients treated due to neuropathic pain, ADs are used much more often than BDAs and hypnotics. Depression was well controlled, while anxiety was identified as a possible uncontrolled therapeutic problem in these patients, despite the correlation between the frequency of AD and hypnotics usage and the severity of anxiety. We also found that women show a higher level of intensity in both anxiety and depression, but this does not influence the frequency of their being administered ADs, BDAs, and hypnotics.This finding suggests the need for evaluating the emotional state of patients treated for neuropathic pain. Selected ADs could possibly be considered as a first choice of pharmacotherapy in a depressed and anxious patient. The limited influence of the pharmacotherapy applied on the anxiety level in this group of patients suggests the need to put more emphasis on psychological treatment options. These options should also be considered more widely in neuropathic pain treatment in women.


Managing postoperative pain even after laparoscopic groin hernia repair still remains an interesting challenge for clinicians especially for patients of high risk. Plenty of operative techniques and analgesic methods have been proposed in order to minimize postoperative pain after laparoscopic groin hernia repair. The aim of the present study is to compare transverse abdominis plane (TAP)-block with local analgesic infiltration at trocar entry sites in the terms of reducing postoperative pain.Patients that underwent laparoscopic trans-abdominal pre-peritoneal (TAPP) groin hernia repair in a high-volume university hospital were included. Patients were divided in two groups depending on the analgesic method used. Pain was assessed using Visual Numerical Scale (VNS) score.p < 0.05) compared to local analgesic infiltration at the trocar insertion site at 6, 12 and 24 h after surgery (p < 0.05). In addition, pain reduction was more effective in rest rather than in motion for both analgesic methods.Thirty patients were included. Intraoperative TAP-block seemed to be superior in terms of decreasing pain at the hernia area and at the trocar insertion site (Intraoperative TAP-block under direct vision seems to be an effective, fast and easy technique in order to reduce postoperative pain after laparoscopic groin hernia repair, but more studies are required to validate these results in a prospective and randomized context. Groin hernia repair was the most common surgical operation during 2018, as more than 20 million procedures had been performed worldwide -guided transverse abdominis plane (TAP) blocking might have promising outcomes in alleviating postoperative pain , 7. DuriPatients that underwent laparoscopic trans-abdominal pre-peritoneal (TAPP) groin hernia repair with polypropylene mesh placement under general anesthesia at a university surgical department from January 2019 to April 2019 were included. Exclusion criteria were complicated hernias , immunosuppression, surgery within the last 3 months, chronic pain at the area, anticoagulation therapy, inability to answer or sign a consent form, cognitive disorders or refusal to sign a consent form and inability to undergo surgical procedures under general anesthesia.Patients were retrospectively enrolled in our study. The study was performed according to the World Medical Association Declaration of Helsinki and ethical approval had been received by the institutional ethics committees. Our study was based on the evaluation of the clinical data of patients that were kept in record after informed consent obtainment, according to the institutions' policy.The study group consisted of patients that received intra-operative TAP-block under direct vision, whereas the control group consisted of patients that underwent local infiltration of anesthetic agent at the working trocars entry points. The aim of TAP-block was to deposit local anesthetic in the plane between the internal oblique and transversus abdominis muscles aiming the spinal nerves that pass along this plane. For TAP-block, 15 mL of 0.25% bupivacaine hydrochloride was used after laparoscopic procedures. In bilateral hernias, 10 mL of local anesthetic was injected in each side, due to the maximum dose allowed for each patient. The entry point of local anesthetic was the lumbar triangle of Petit, between the lower costal margin and iliac crest. It is bound anteriorly by the external oblique muscle and posteriorly by the latissimus dorsi muscle . Surgicap < 0.05.Power analysis was utilized to determine the minimum sufficient number of participants in order to achieve statistical significance. On this basis, a total sample of 30 patients (15 patients in each arm) was considered sufficient at bilateral levels of significance of 0.05. Mean and median values, standard deviations (SD) and interquartile ranges were used to describe quantitative variables. Absolute (N) and relative (%) frequencies were used to describe qualitative variables. Two-way repeated analysis (two-way repeated ANOVA) was used in order to investigate differences among the methods of anesthesia, infusion points and postoperative time intervals. Due to abnormality of data distribution, logarithmic transformations of the variables were performed. Analysis was performed using the SPSS version 22.0 software . The statistical significance was set at a value of Thirty patients, 29 men (96.7%) and 1 woman (3.3%), were included in the present study. Inguinal hernia was present in 96.7% of patients, mainly on the right side (51.7%), whereas 3.3% of patients presented with femoral hernia on the left side. The demographic characteristics of included patients are presented in Pain scores at rest near the trocar insertion site and near the hernia area according to the 10-point VAS scale are presented in p < 0.001).The infiltration of trocar entry points with local analgesic agents was associated with greater pain scores at the trocar site compared to the TAP-block at 6, 12 and 24 h postoperatively (p = 0.032), whereas pain scores at 24 h after surgery were not significantly higher for trocar site infiltration with local analgesics (p = 0.072).Regarding pain at hernia area, it was demonstrated that infiltration of trocar sites with local analgesics was associated with significantly higher pain scores compared to TAP-block at 6 and 12 h after surgery (p < 0.001).Using infiltration of trocar entry sites with local analgesics, pain scores were significantly higher near the trocar insertion site at 6, 12 and 24 h postoperatively compared to the hernia area .The utilization of TAP-block was associated with higher pain scores at the trocar placement sites at 6, 12 and 24 h postoperatively, compared to the pain at hernia site ((p > 0.05). In addition, the degree of pain alteration was similar regardless to the pain assessment site and the anesthetic method (p > 0.05)  or assessing pain at both areas (trocar insertion point and hernia area)  > 0.05) , 3.Pain scores during movement near the trocar insertion site and near the hernia area according to the 10-point VAS scale are presented in p < 0.001).The infiltration of trocar entry points with local analgesic agents was associated with greater pain scores at the trocar site compared to the TAP-block at 6, 12 and 24 h postoperatively (p < 0.001), as well as at 24 h postoperatively (p = 0.003).Regarding pain at hernia area, it was demonstrated that infiltration of trocar sites with local analgesics was associated with significantly higher pain scores compared to TAP-block at 6 and 12 h after surgery (p < 0.001).Using infiltration of trocar entry sites with local analgesics, pain scores were significantly higher near the trocar insertion site at 6, 12 and 24 h postoperatively compared to the hernia area (p < 0.001).The utilization of TAP-block was associated with higher pain scores at the trocar placement sites at 6, 12 and 24 h postoperatively, compared to the pain at hernia site ((p > 0.05). When TAP-block was utilized, no significant changes in pain scores over time at the hernia site was reported (p > 0.05). However, near the area of trocar insertion, pain scores at 24 h were significantly greater compared to 6 and 12 h after surgery . In addition, pain scores at 12 h were significantly higher compared to 6 h after surgery (p < 0.05).No significant differences were observed between pain scores at 6, 12 and 24 h after surgery using local infiltration of trocar sites at both pain assessment areas (trocar insertion point and hernia area) p = 0.019), as a significant change was demonstrated when pain was assessed near the trocar insertion site and TAP-block was utilized .Similar results have been reported in previous studies , 13. NevThe small number of patients who were recruited in the present study after retrospective search of the records of a high-volume university hospital demonstrate the limited familiarity with this technique. However, the promising results of our study could pave the way to a more systematic use of this technique. The future utilization of this technique in a large number of patients could highlight its effectiveness and potential difficulties that need to be addressed. In contrast to modern but expensive and scarcely available surgical options for groin hernia repair, such as robotic surgery, nerve blockade under direct vision offers an effective modification of laparoscopic groin hernia repair while enhancing trainee education and improving patients' outcomes . FurtherReduction of postoperative pain contributes to the faster recovery of patients and return to their daily activities. Data from the US demosntrate that post-operative pain still remains a serious problem for elderly patients even nowadays . PostopeThe analgesic technique proposed in our study helps to reduce total health cost by relieving health system from additional cost of special equipment or training in ultrasound techniques. In addition, this technique promotes creating one-day surgery centers, which are expected to relieve surgery clinics and further reduce the cost of treatment. However, patient discharge after groin hernia repair must be determined by the principles of evidence-based medicine, rather than by the estimated cost .The present study includes a small sample of patients, that was a result of power statistical analysis, which is an important limitation. In addition, the lack of randomization and the retrospective nature of our investigation seem to be limitations as well. However, our study demonstrated that TAP-block under direct vision could be more effective compared to local analgesic infiltration in reducing postoperative pain at the trocar insertion site after laparoscopic groin hernia repair. To the best of our knowledge, it is the first pilot clinical study which demonstrates the effect of this technique in laparoscopic groin hernia repair. Therefore, a large, prospective, multicenter, doubly randomized study, with a homogeneous sample of patients, materials and techniques, could make these outcomes more robust. Allocating legs of such a study to the estimation of costs, patient satisfaction and educational outcomes would be useful as well.Intraoperative TAP-block under direct vision seems to be an effective, fast and easy technique in order to reduce postoperative pain after laparoscopic groin hernia repair instead of using local analgesic infiltration. In comparison to TAP-block under US-guidance, this technique seems to be superior in the terms of feasibility, speed and reproductivity. However, more studies are required to validate these results in a prospective and randomized context.The raw data supporting the conclusions of this article will be made available by the authors, without undue reservation.The studies involving human participants were reviewed and approved by IRB - Hippocration General Hospital of Athens. Written informed consent to participate in this study was provided by the participants' legal guardian/next of kin.AC: study design, data analysis, and writing. MF and GG: data collection and writing. EK: writing. TX: study design. NM: data analysis and writing. All authors contributed to the article and approved the submitted version.This work was supported by National and Kapodistrian University of Athens Special Account for Research Grants (UoA/S.A.R.G.).The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.All claims expressed in this article are solely those of the authors and do not necessarily represent those of their affiliated organizations, or those of the publisher, the editors and the reviewers. Any product that may be evaluated in this article, or claim that may be made by its manufacturer, is not guaranteed or endorsed by the publisher.