Treatment of patients with failed back surgery syndrome (FBSS) with predominant low back pain (LBP) remains challenging. High-frequency spinal cord stimulation (HF10 SCS) is believed to achieve significant pain reduction. We aimed to evaluate the real-life efficacy of HF-10 SCS in a tertiary spine center. A prospective observational study of all patients with FBSS and predominant LBP who underwent HF-10 SCS surgery was performed between 2016 and 2018. Patients > 18 years with Visual Analogue Scale (VAS) scores of ≥ 5 for LBP and pain duration > 6 months under stable medication were implanted percutaneous under general anesthesia and a trial phase of 7–14 days was accomplished. Primary end point was a successful trial defined as ≥ 50% VAS score reduction for LBP. Thirty-four of 39 (85%) subjects had a successful trial. Fifty-three percent were female and the mean age was 69 years. Median follow-up lasted for 10 months. Devices were removed after a median of 10 months in 5 cases. Remaining 29 patients stated significant VAS score reduction for LBP from 8.1 to 2.9 and VAS for leg pain from 4.9 to 2.2. Twenty-four percent of all patients were able to discontinue their opioids. Eight of 9 patients (89%) with signs of adjacent disc disease and 7 of 10 (70%) patients with hardware failure were successfully implanted with significant VAS reduction for LBP. HF-10 SCS achieves significant pain reduction in most patients with FBSS and predominant LBP. It might be an efficient alternative to revision surgery. Failed back surgery syndrome (FBSS) is defined as a persistent or recurrent pain, mainly in the lower back and/or legs, even after previous anatomically successful spinal surgery . It is aA prospective observational study of all consecutive patients with FBSS with predominant LBP (VAS ≥ 5) treated between January 2016 and November 2018 was performed in a single high-volume spine center. The study was performed according to the Declaration of Helsinki and ethical consent was obtained (registration nr. 409/13).Inclusion criteria were prior medical history of thoracic or lumbar surgeries with either decompression alone or instrumentation and decompression, at least 6 months of persistent intractable LBP with or without neuropathic component under conservative pain treatment with or without opioids. A psychological assessment was performed preoperatively to rule out major depression, bipolar or psychotic disorder. Exclusion criteria were age < 18 years, no prior spinal surgeries, a causal correlate on spinal imaging , and no prior regular pain medication or extensive conservative treatment. Patients meeting all criteria were enrolled in our prospective study and first underwent a trial phase with percutaneous epidural placement of two HF10-SCS leads  in general anesthesia at the Th8-Th10 level  of the implanted patients were female, and 47% (n = 16) were male. The mean age was 69 years [range 31–86]. Median age of the implanted patients was 69 years [range 31–86] while the median age of the explanted patients cohort was 72 years [range 49–81] (p = 0.669). VAS scores for back and leg pain preoperatively were equally distributed in both groups of implanted and explanted patients . The percutaneous lead implantation for the successfully implanted patients had a mean duration of 63 min [range 34–107 min] and the IPG surgery a mean duration of 32 min [range 11–94 min]. In patients, who were later explanted due to loss of treatment response, initial leads implantation lasted a mean of 103 min [range 67–138 min], which was statistically significantly longer (p = 0.018). IPG implantation in those patients lasted in mean 31 min [range 20–37]. Median follow-up examinations were performed after 10 months [range 4–24] for all patients.In total, 34 of 39 patients (85%) were initially successfully implanted with HF10-SCS after a mean time of 21 days [range 7–84] after initial testing  experienced a trial failure (Table 5% experip = 0.574), age (p = 0.669), or sex (p = 0.798) and the rate of explantation in our patient cohort. The remaining 29 patients (74%) had a significant and persistent pain reduction for LBP from VAS 8.1 to 2.9 and limb pain from VAS 4.9 to 2.2  revealed that SVA was pathologically increased in explanted patients and marginal in those with negative trials . This might have correlated with a mechanical component of low back pain on axial load in those patients, which potentially exceeded or intensified the neuropathic pain as well. However, it is still debatable whether sagittal imbalance is the cause of low back pain or whether it only correlated with postoperative mechanical complications. Furthermore, 19 of 28 (68%) implanted patients, 4 of 5 (80%) explanted patients, and 4 of 6 negative trials (67%) used to have neuropathic leg pain prior to surgery, which also improved with HF10 SCS therapy (VAS reduction of leg pain from 7 to 3). There were only 4 of 28 (14%) implanted patients and 1 of 6 (17%) with negative trials who were previously treated with discectomy without spinal fusion. Five of 28 (18%) of the implanted patients and 1 of 6 (17%) of those with negative trials suffered from low back pain without neuropathic component, though there was no significant difference for all subgroups considering the lumbar and leg pain outcome with SCS therapy (Table Twenty-five percent (10/40) of the initially recruited patients did not take prior opioid medication before initiation of the HF10-SCS treatment and they neither required any opioids postoperatively. Twenty-four percent (7/29) of the permanently implanted patients were able to completely and permanently discontinue their opioid medication on follow-up examination, relying on NSAID analgesics occasionally. The majority of patients were on gabapentin or pregabalin medication in combination with SCS therapy  due to neuropathic pain. This type of medication was continued by all patients on follow-up.We monitored patients immediately postoperatively and on follow-up examinations through X-ray imaging in order to detect any hardware failure. Twenty-four percent (7/29) of all permanently implanted patients experienced a lead migration on X-ray imaging during follow-up examinations Table , Fig. 4.Twenty-four patients 62%) had received dorsal or dorsoventral lumbar or thoracolumbar instrumentations and the remaining 15 patients 38%) were treated with discectomies or decompression surgeries prior to SCS therapy  for percutaneous epidural lead placement in patients who were later explanted. Even though X-ray imaging in those cases confirmed correct lead placement intra- and postoperatively, an extensive scar tissue in the spinal canal due to prior surgeries might have led to lead placement difficulties and later therapy loss.Treatment of patients with concomitant degenerative spine disease and Parkinson’s disease remains very challenging. In our series, two patients with Parkinson’s disease were ultimately non-responders to HF-10 therapy. One patient had a negative test trial (patient 6) and the second patient experienced loss of initial treatment effect following 3 months after IPG implantation. In recent literature, there are only a few case reports and case series dealing with SCS treatment in patients with Parkinson’s disease. However, Parkinson’s should not be an exclusion criterion as several patients reportedly improved in walking posture, rigidity, and pain intensity through spinal cord stimulation , 9.In our study, a high number of patients (24%) were able to discontinue their opioids on follow-up. Those are similar results to larger studies like the SENZA trial, in which over one-third of all subjects who received HF10-SCS therapy were able to reduce or wean off their opioids despite an average of 13 years of prior chronic pain [We did not encounter any severe mechanical complications, e.g., lead fracture or disconnection, which has a reported incidence between 5 and 9%. We did not observe clinically evident treatment loss due to lead migration even though on follow-up imaging we detected a moderate lead migration in 24% of all permanently implanted patients. Lead migration has a reported incidence in the literature between 0 and 27% . These hSeveral studies have demonstrated the benefit of novel SCS therapies over traditional low-frequency SCS for the treatment of patients with chronic low back and/or leg pain. SENZA-RCT showed that paresthesia-free HF10-SCS was superior to low-frequency stimulation for treatment of chronic low back pain with leg pain. The SUNBURST crossover trial recently found that high-frequency burst stimulation was preferred over low-frequency tonic SCS with patients citing better pain relief and a preference for paresthesia-free SCS . HoweverHF10-SCS therapy is able to achieve highly satisfactory pain reduction in most patients with FBSS with predominant mechanical LBP. In summary, HF10-SCS therapy may contribute to an efficient, cost-effective, and less invasive alternative to revision spine surgery in patients with LBP without compression of neural structures or apparent instability.


IntroductionStereotactic radiosurgery for trigeminal neuralgia (TN) has gained interest among patients who are not suitable for surgical procedures. Although two target zones are more recognized - dorsal root entry zone (DREZ) and retrogasserian zone (RGZ) - the optimal targeting technique remains controversial in terms of clinical outcomes and rates of complications. Therefore, various modifications to the radiosurgical technique for TN have been made.ObjectiveThis study aimed to determine the differences in shoot location  regarding effectiveness and adverse effects in patients with medically refractory TN. Additionally, we evaluated the effect of the integral dose (ID) on treatment outcomes and complications.MethodsWe present a retrospective cohort study of 49 patients with primary, drug-resistant TN treated with gamma knife radiosurgery targeting the distal and proximal parts of the nerve regarding the DREZ with a prescription dose of 90 Gy (80 to 96 Gy). A subset of these patients (n=38) where the ID could be measured to the nerve was correlated to treatment outcomes and complications.Results2=0.0826, degree of freedom=1, p=0.773). Treatment outcomes using higher ID were better in the RGZ than DREZ , and a significant association was found between a higher ID delivered to the nerve and the development of complications (p=0.02).The median follow-up time was 36 months for RGZ and 51 months for DREZ targets. Neurovascular conflict was identified in 87.5% of the RGZ group and 88.2% of the DREZ group. Using the Barrow Neurological Institute (BNI) pain score, 26 (81.3%) RGZ and 12 (70.6%) DREZ patients were successfully treated . Seven (21.9%) RGZ and eight (47.1%) DREZ patients reported complete pain relief without medication (BNI I). Time response was 22.3 days for RGZ and 34.1 days for DREZ (p=0.277). There were 10 (31.3%) patients in the RGZ group with associated complications versus six (35.3%) patients in the DREZ group (χConclusionBased on the obtained results, the RGZ was a more effective targeting area with better treatment outcomes without significant differences in complication rates than DREZ. A higher ID at the RGZ than DREZ had a greater therapeutical effect. Further investigation regarding the optimal target area along the ID delivered and clinical outcomes are required. Primary trigeminal neuralgia (TN) is usually a unilateral, neuropathic pain in the trigeminal nerve distribution that can be severe and refractory to medical treatment . It is aSeveral studies have reinforced the safety and efficacy of SRS as a treatment option for TN ,7-11, anThe radiobiological effect of radiation in the trigeminal nerve plays a role in treatment outcomes and might be determined by the amount of energy absorbed by the tissue, a concept known as integral dose (ID). The ID for gamma knife technology is calculated by the mean dose delivered multiplied by the volume of tissue inside the 50% isodose line (IDL) divided by 1,000 and expressed in millijoules (mJ) . AlthougThe purposes of this study are to compare a more distal target (RGZ) to a more proximal target (DREZ) with regards to effectiveness and paresthesia in patients with medically refractory TN and to evaluate the effect of the ID on treatment outcomes and complications.The present study is a retrospective cohort study conducted from March 2014 to February 2021, assessing all cases of TN treated with radiosurgery with at least six months of follow-up at the International Cancer Center in El Salvador. During this period, 33 of 82 patients treated for TN were excluded as 16 were lost to follow-up, 13 had secondary TN, two patients had treatment planning over computed tomography, and two had previously received SRS to the same trigeminal nerve. Therefore, 49 patients were eligible for the study. Preprocedural diagnosis, clinical presentation, time from symptom onset to treatment date, affected side, and medication use before SRS were reviewed, and patients were assigned into two different groups depending on their targeted treatment zone - RGZ or DREZ - and dose registered by distance (in mm) from the DREZ to differentiate dosimetrically one from another regardless of nerve length or anatomy.Radiosurgical techniqueAll patients were treated with Infini™ , a rotating gamma-ray unit. Magnetic resonance imaging was obtained with stereotactic frame rigidity fixed to the head under local anesthesia, and we obtained T1-weighted multiplanar gradient recall gadolinium with 1-mm thickness slices in the axial orientation as well as a three-dimensional constructive interference in steady state (CISS) that also had a 1-mm thickness per slice in the axial orientation. Radiation doses ranging from 80 to 96 Gy were prescribed to the 100% isodose line using a single 4-mm isocenter positioned at the RGZ or DREZ of the affected trigeminal nerve.Target definition and shot placementThe DREZ consisted of an area 3 mm anterior to where the nerve emerges from the pons and a transitional area along the trigeminal nerve where the myelin surrounding the axons changes from peripheral myelin produced by the Schwann cells to the central myelin produced by oligodendrocytes . The RGZFor the DREZ target, measurements were made from the brainstem along the nerve, typically 3 mm to 4 mm anteriorly from its emergence from the pons, and, for the isocenter of the shot, the 20 Gy isodose line was intended to cover part of the brainstem at the nerve root entry. For the RGZ shot, the intracranial ganglion was identified, and the shot was placed at the cisternal level behind the gasserian ganglion Figure .For radiosurgical treatment and data collection, informed consent was obtained from all patients. This study was approved by the local institutional ethical committee and review board of the International Cancer Center.Follow-up and outcome assessments of pain characteristics were evaluated using the Barrow Neurological Institute (BNI) Scale, which classifies pain in six grades as follows: BNI I = no pain, no medication; BNI II = occasional pain without medications; BNI IIIa = no pain, continued medications; BNI IIIb = persistent pain, controlled with medications; BNI IV = some pain, not controlled with medications; and BNI V = severe pain, no pain relief . PatientMedication use before and after SRS was compared, and categories were labeled depending on the amount of medication used to determine if patients could reduce the amount of medication used before SRS.To detect secondary effects related to SRS, patients were asked to describe any adverse effects they could relate to treatment. Trigeminal sensory loss after SRS was evaluated using the BNI Numbness Scale (BNI-NS), where BNI-NS I is defined as no trigeminal sensory loss, BNI-NS II is mild but not bothersome trigeminal sensory loss, BNI-NS III is bothersome trigeminal sensory loss, and BNI-IV is very bothersome trigeminal sensory loss.To further understand the possible correlation of ID and the duration of pain relief, the response to treatment and related complications were measured in 38 patients (77.5%). The ID is the product of the mean dose and the target volume  and was Patients follow-up was made at one and three months after treatment and every six months after that. Information on pain characteristics, the time interval for treatment response, changes in medication use, recurrence, complications, and quality of life were obtained via in-person or phone evaluations.The Shapiro Wilks test was applied to determine the normal distribution of values. Based on value distribution, multivariate analysis was made for categorical and continuous variables. P-values < 0.05 indicate statistical significance.Patient characteristicsPatient and clinical characteristics are shown in Table The RGZ group consisted of 32 patients (65.3%), of whom 23 were female (71.9%), and nine were men (28.1%) with a mean age of 56 years . Eighteen patients (56.3%) reported pain on the left trigeminal nerve and 14 (43.8%) on the right side. The DREZ group consisted of 17 patients (34.7%), 13 were female (76.5%), and four were male (23.5%) with a mean age of 56 years , five patients (29.4%) reported pain on the left trigeminal nerve, and 12 (70.6%) reported pain on the right side. Neurovascular conflict was identified in 28 patients (87.5%) of the RGZ group and 15 patients (88.2%) of the DREZ group. The median duration of pain to the day of SRS was 72 months  for RGZ and 72 months  for DREZ.Treatment outcomes are shown in Table The mean length of follow-up for patients in the RGZ group was 36.0 months  and 51.0 months  for the DREZ group. Both groups received a median prescription dose of 90 Gy, and doses ranged from 80 to 96 Gy in the DREZ group and 80 to 94 Gy in the RGZ group . Target definition apart from anatomical identification was also separated by dose measurement at 1 mm, 2 mm, 3 mm, and 4 mm of the DREZ in each group; median dose to the RGZ at 1 mm was 11.6 Gy , at 2 mm was 18.4 Gy , at 3 mm was 29.2 Gy , and at 4 mm was 41.5 Gy (range 8.2 to 83.5 Gy). The median dose at 1 mm from DREZ was 29.5 Gy , at 2 mm was 43.9 Gy , at 3 mm was 60.2 Gy , and at 4 mm was 69.5 Gy ; such findings reinforce that target location, and dose variation between the RGZ and DREZ could be determined despite anatomical variations that the nerve might have in the case series.2=4.8, degrees of freedom [d.f]=1, p=0.028). By three months after SRS, 29 (90.6%) patients had responded to treatment, and three (9.4%) never responded in the RGZ, while 14 DREZ patients (82.4%) had responded between one and three months after treatment, and two patients responded after three months. At last follow-up, 26 patients from RGZ (81.3%) and 12 from DREZ (70.6%) were considered successful treatments ; while six RGZ (18.8%) and five DREZ patients (29.4%) had treatment failure (BNI IV and V). Seven RGZ (21.9%) and eight DREZ patients (47.1%) reported complete pain relief without medication use (BNI I). Three RGZ (9.4%) and no DREZ patients (0%) had occasional pain that did not require medication use (BNI II). Six RGZ (18.8%) and two DREZ patients (11.8%) had no pain with continued medication use (BNI IIIa), and 10 RGZ (31.3%) and two DREZ patients (11.8%) had persistent pain controlled with medication (BNI IIIb).Initial pain response at one month after SRS was achieved in 31 patients according to the BNI (I-IIIb), 21 (65.6%) patients from the more distal group, and nine (52.9%) from the proximal group . The mean response to treatment was 22.3 days  for RGZ and 34.1 days  for DREZ patients .Of all patients included in the study, eight (16.3%) had a response to treatment in 24 hours. Seven (87.5%) were from the RGZ group, and one (12.5%) was from DREZ  met these criteria.In terms of pain frequency, 11 (34.4%) RGZ and eight (47.1%) DREZ patients had no pain in the last follow-up, eight (25%) RGZ and two (11.8%) DREZ patients reported spending several months without pain, and three (9.4%) RGZ and one (5.9%) DREZ patient had pain several times per month after treatment. Patients who reported having no pain or pain within months were considered to have treatment success, and 22 (68.8%) RGZ and 11 (64.7%) DREZ patients . The median time of recurrence was 120 days  for RGZ and 60 days  for DREZ patients .Among patients who did not respond to treatment (BNI IV and V), five (15.6%) RGZ and four (23.5%) DREZ patients had some pain not controlled with medication, and two (6.3%) RGZ and one (5.9%) DREZ patient had severe pain and no pain relief with medication use, respectively. Pain recurrence was seen in seven (21.9%) RGZ patients and five (29.4%) DREZ patients .During the last follow-up, 25 (78.1%) RGZ and 14 (84.2%) DREZ patients reported an improvement in their quality of life, while seven (21.8%) RGZ and three (17.7%) DREZ patients did not . No further complications were reported among study participants.With regards to treatment complications and according to the BNI-NS, 22 (68.9%) RGZ and 11 (64.7%) DREZ patients had no trigeminal sensory loss (BNI-NS I), and seven (21.9%) patients from RGZ and six (35.3%) from DREZ reported mild but not bothersome trigeminal sensory loss (BNI-NS II). Three (9.4%) patients from RGZ reported having bothersome trigeminal sensory loss (BNI-NS III), while no patients (0%) from DREZ reported having such complication. There were 10 (31.3%) patients in the RGZ group with associated complications versus six (35.3%) patients in the DREZ  were medicated or had failed first-line treatment with carbamazepine and could be taking other antiepileptic medicine. The most common medications were gabapentin or pregabalin. Several patients (12.5%) were treated with antiepileptic drugs and non-steroidal anti-inflammatory drugs (NSAIDS), and 28% received the previous two medications and opioid regimens. In the DREZ group, one patient (5.8%) received no medicine at the time of treatment, and 35.3% of patients in the DREZ group were treated with carbamazepine or another antiepileptic drug; 11.8% received only NSAIDS, 11.8% received antiepileptic and opioid regimens, 5.8% received antiepileptic drugs and NSAIDS, and 29.4% received antiepileptic drugs, NSAIDS, and opioid regimens. 2=8, d.f=1, p=0.004).After radiosurgery, eight (25%) RGZ patients were able to stop medication use due to a good response to treatment, and 15 (46.9%) were able to alleviate pain using only one medication. Three (9.4%) and six (18.8%) patients continued with two and three types of medication after treatment, respectively . We found a significant association among RGZ and DREZ patients when comparing medication use before and after radiosurgery.From the DREZ group, only one (6.3%) patient did not use any type of medication to alleviate pain before radiosurgery, seven (41.2%) used one medication, four (23.5%) used two types of medication, and five (29.4%) used three different medications to relieve pain. After radiosurgery, eight (47.1%) patients were able to control their pain without any medication, and six (35.3%) could alleviate pain using one medication. One (5.9%) and two (11.8%) patients continued using two and three medications to alleviate their pain, respectively , the ID could be further calculated to determine if there was an existing correlation between the ID delivered to the trigeminal nerve, response to treatment, and the development of complications  and 32.7 mm3  for RGZ . Twenty-two RGZ and 16 DREZ patients were distributed based on their ID value, and complications and treatment outcomes were compared between groups. Patients from DREZ who received low ID developed more complications than those targeted to the RGZ with similar ID . DREZ patients receiving high ID did not develop any complications associated with treatment. There was a significant association between the ID delivered to the nerve and complications post-treatment .ID values ranged from 1 to 4.3 mJ; median ID was 2 mJ; therefore, ID was further classified as low ID < 2.0 mJ and high ID ≳ 2.0 mJ. Mean nerve volume inside the 50% IDL for DREZ was 30.6 mm2=1.68, d.f=1, p=0.194). On the contrary, DREZ patients with low ID had better treatment outcomes than RGZ patients . One patient (9.1%) from RGZ receiving high ID had paresthesia but a good response to treatment. Treatment outcomes with high ID were better in RGZ than DREZ . There was no significant difference between the ID and treatment outcomes . The dose delivered to the DREZ was lower than the RGZ . Mean IDs were compared between groups (2.10 in RGZ vs. 1.88 in DREZ), and there was no significant difference between the ID delivered to the DREZ and the RGZ .Regarding the scoping review of the literature, we identified 28,628 records. Fifteen studies were selected based on their titles and abstracts, and after full-text evaluation, only three studies remained Table  12-14].-14.12-14Gamma knife radiosurgery (GKRS) has been proposed as an effective treatment option for patients with drug-resistant TN. Numerous studies have been published demonstrating SRS effectiveness towards reducing trigeminal pain, including the present study ,7-11, buTargeting preferences have changed over time. Leksell initially used the trigeminal ganglion as a treatment target ; other aOur study compares treatment outcomes and adverse effects between both target zones. Based on our results, RGZ is preferable to DREZ, a position supported by existing evidence showing that targeting such areas provides better pain control than DREZ but with equal complication rates. Dose measurement at 1 mm, 2 mm, 3 mm, and 4 mm from the DREZ contributed to finding a more precise target location based on the amount of Gy per mm of the nerve. This helped in differentiating between an anterior, mid-cisternal, or posterior targeting zone regarding the two strategies, regardless of nerve length.Regarding pain control, Kondziolka et al.  proposedWe were able to demonstrate that there is a difference between targeting the RGZ and DREZ. Treatment success was higher among RGZ patients than DREZ . Most patients from our series did continue using some type of medication despite having a good response to SRS; drug discontinuation was more evident among DREZ patients than RGZ patients . Park et al. compared RGZ with DREZ and reported that RGZ, as a target, was more effective in providing pain control than DREZ (93.8% vs 87%) and an earlier response to treatment (4.1 weeks with RGZ vs. 6.4 weeks with DREZ) . ImportaTime response to radiosurgery varies among patients. Gorgulho stated that the pace of pain response might depend on the extension of demyelinated areas submitted to high-dose radiation, and pain outcomes tend to be better when the isocenter is brought closer to the brainstem . TargeteRegarding immediate response, 16.3% of the patients reported having a response to treatment and pain improvement within the first 24 hours of treatment (seven from the RGZ and one from the DREZ group). A neuro-radiation modulatory effect  or even The ID was first introduced by Mayneord over 60 years ago, affirming that the measurement of radiation for medical purposes is primarily concerned with the measurement of the total energy absorbed by the target volume of a given tissue (volume × mean dose). By definition, the ID is dependent on the volume of the tissue receiving radiation; therefore, larger volumes of tissue absorb more energy than smaller volumes of tissue, despite receiving the same amount of dose . RadiosuThe rate of trigeminal sensory loss in our study is similar to the complication rate reported by others -14. MatsShrivastava et al. studied the relationship between the ID and the maintenance of pain relief and found a positive correlation between the ID within the 50% IDL and the duration of pain relief (p=0.004) . HoweverMousavi et al. evaluated the effect of the ID in a series of 155 patients treated with SRS for TN. Patients were stratified into three groups based on the ID value: low, medium, or high. Patients receiving medium ID (1.4-2.7 mJ) had a better response to treatment and pain relief than those receiving the low or high ID, and those who received higher ID had higher rates of sensory dysfunction than those who received medium or lower doses [After comparing two different target zones, the ID delivered to the nerve on each targeted zone, complications, and treatment outcomes, there is a significant correlation between the ID higher than 2 mJ and the development of complications (p=0.026).We demonstrated a significant correlation between the targeted zone and treatment outcome in BNI (p=0.02). Also, a higher or lower ID does not correlate with a better or worse response to treatment (p=0.194). In our experience, patients targeted to the DREZ receiving low ID and patients targeted to the RGZ receiving high ID had good responses to treatment .Regarding timing between symptom onset to the date of GKRS, several studies ,4,23,29 Lastly, the DREZ shoot occurred during the initial years of the Gamma Ray radiosurgery program using cobalt activity, and therefore, the dose rate was at its highest in comparison to the RGZ shoot, which is currently favored given its lower dose rate due to cobalt decay. Therefore, we did not observe better outcomes attributable to higher dose rates as suggested by other authors .There are several potential limitations to this study. First, it is a single-center experience with a retrospective design that inherently limits its power and generalizability, loss of information limited our patient sample and we were unable to measure the ID in the complete set of patients. Follow-up duration was short, and therefore, cases of recurrence were not completely identified since studies with long-term follow-up state that the clinical efficacy of SRS decreases with time. However, given the possibility of recurrence in TN, the short follow-up of the current series, and the study designs of the published studies, randomized control trials comparing two target zones remain the ideal method to determine the rate and duration of pain relief and the associated complications for each target zone.Although the DREZ and RGZ are two stated treatment areas for TN, controversies remain on the more effective target zone when using SRS. Based on our series report with a mean follow-up of three years and in accordance with some of the current literature, our results suggest that RGZ is a more effective targeting area with better treatment outcomes without significant difference in complication rates than DREZ. Calculating the ID might contribute to optimal planning with radiation dosage based on the nerve’s volume to provide lower rates of paresthesia and procuring lower IDs. However, a further investigation between the ID delivered and clinical outcomes is advisable.


Management of neuropathic pain in people with diabetes has been widely investigated. However, little attention was paid to address ischemic-related pain in patients with diabetes mellitus who suffered from chronic limb-threatening ischemia (CLTI), the end stage of lower extremity arterial disease (LEAD). Pain management has a tremendous influence on patients' quality of life and prognosis. Poor management of this type of pain owing to the lack of full understanding undermines patients' physical and mental quality of life, which often results in a grim prognosis, such as depression, myocardial infarction, lower limb amputation, and even mortality. In the present article, we review the current strategy in the pain management of diabetes-related CLTI. The endovascular therapy, pharmacological therapies, and other optional methods could be selected following comprehensive assessments to mitigate ischemic-related pain, in line with our current clinical practice. It is very important for clinicians and patients to strengthen the understanding and build intervention strategy in ischemic pain management and possible adverse consequence. Lower extremity arterial disease (LEAD) in diabetes is a leading cause of limb loss and has a profoundly negative impact on quality of life and early mortality . AlthougAlthough the pain is an important issue for most patients with CLI, it is often poorly managed and mismanaged . Many inMoreover, ischemic ulcers carried higher mortality risk than neuropathic ulcers in patients with DM, although neuropathic ulcers induce considerable morbidity than ischemic ulcers . In addiPresently, no randomized clinical trial has been conducted, and no specific practice recommendation has been provided in the management of ischemic pain in patients with CLI . It is dTherefore, we intend to discuss the current therapeutic approach for the management of ischemic-related pain in patients with diabetes-related CLTI through our clinical cases. The purpose of this study was to summarize different interventions available for the management of such condition, including the acceptable option for limb salvage with endovascular therapy and palliative care with pharmacotherapies in patients with CLTI.Despite the first definition of CLI being published in 1982, the discussion remains open about the hemodynamic criteria . The emeIt is estimated that up to 1 in 10 patients with LEAD has CLTI. The natural history of CTLI is of unpredictable nature and variable. Progression of CLTI from asymptomatic LEAD or IC has been estimated to be at least 5-10% within 5 years, while as much as 50% of patients diagnosed with CLTI may not even have previous history of LEAD . The cliMajority of patients with diabetes-related CLTI may present also with nonhealing ischemic ulcer to gangrene (Fontaine stage IV) . In the Chronic ischemic pain is one of the most frequent causes of pain in the lower extremities . In partThe characteristic and clinical appearance of chronic ischemic pain in LEAD usually cover from nociceptive pain in patients with IC to predominantly neuropathic pain in patients with CLTI. It has been shown that questionnaires  might be a helpful tool to investigate and diagnose ischemic pain .Previous studies have indicated that persons with diabetic lower extremity complications have 5-year mortality rates similar to many common types of cancer . The impIn recent years, three leading vascular societies including the European Society for Vascular Surgery, the Society for Vascular Surgery, and the World Federation of Vascular Societies were determined to launch the Global Vascular Guidelines (GVS) in the effort to address the appropriate management of CLTI. Successful revascularization in CLTI, particularly in patients with tissue loss, nearly always requires reperfusion to the foot to promote wound healing and pain relief. Once the clinical manifestations of CLTI such as rest pain, ischemic ulceration, or gangrene have developed, the choice of the intervention such as balloon angioplasty, stenting, and surgical revascularization should be considered in these patients . MoreoveA 68-year-old female with T2DM was admitted to the hospital with a 2-month history of progressing pain and redness in her right foot. She presented a 14-day history of worsening symptoms, especially in the big toe. Physical examination revealed a necrotic slough over the apex of the right hallux , skin teThe diagnosis of CLTI was made on background of clinical symptoms of ischemic rest pain and nonhealing ulceration over two weeks, in conjunction with perfusion studies of the lower limb such as ABI and angiography. The learning point from this case is early revascularization, and appropriate analgesic medication could be an effective treatment to achieve adequate pain relief and limb salvage. This case study exemplifies the importance of revascularization in the management of pain resulted by diabetes-related CLTI.Although revascularization strategy has been emphasized in the treatment of CLTI, the adequacy of pain management is entirely based on the drug of choice. A recent systematic review reported pharmacological therapies for the management of ischemic pain in patients with nonsalvageable CLTI . Six stuA 69-year-old man with T2DM presented to our emergency department for sepsis related with the left foot. The patient had a 3-month history of a progressive ischemic lesion on his left foot, starting from mild cyanosis, nonhealing arterial ulcer to gangrene. The patient's daughter meticulously photographed the course of the lesion over 81 days . SurprisAs the risk of amputation in a deteriorating diabetic foot ulcer is high, when open or endovascular intervention has failed or is not possible, pain management is essential to improve quality of life and disease prognosis. From this case, we can learn that early medical intervention is important to improve clinical outcomes of CLTI.Peripheral angioplasty (PTA) has been established to be the first-choice revascularization procedure in diabetic patients with CLTI. However, there are cases of CLTI that are not considered suitable candidates of angiographies or revascularizations for various reasons . FirstlyOn the other hand, several studies have demonstrated that wound care, as the only treatment for CLTI, can heal approximately 50% of wounds without revascularization . TherefoEndovascular therapy has increasingly become the initial clinical option for the treatment of LEAD, especially for patients with CLTI. Some recent studies have compared the clinical outcomes between open reconstruction and endovascular therapy for CLTI. The BEST-CLI  trial is a prospective, multicenter, multispecialty randomized controlled trial designed to compare the effectiveness of open and endovascular interventions for 2100 patients suffering from CLTI –59. In tThe treatment for CLTI is aimed at relieving ischemic pain, healing ischemic ulcers, avoiding limb loss, improving life quality, and prolonging survival. For pain management in CLTI, guidelines usually recommend a tiered approach, with a “trade off” between benefits and harms , 61, 62.Accordingly, palliative pain management as a component of a care plan or a care focus early in the course of chronic diseases has been emphasized by the WHO . Many stFor CLTI in patients with diabetes, in addition to the use of antithrombotic, lipid-lowering, antihypertensive, and glycemic control drugs, smoking cessation, diet, exercise, and preventive foot care advice with customized diabetic footwear are particularly important in order to achieve a better prognosis and quality of life.Besides the pharmacotherapies, there are many other methods that have been suggested to improve the pain and decrease medication utilization in CLTI. For example, spinal cord stimulation can provide for improvement in pain and potentiate wound healing of ischemic ulcers , 75. A nIn summary, for patients with CLTI, endovascular therapy or surgical bypass surgery should be performed for vascular reconstruction as early as possible. Pharmacological treatments are the basis of the treatment of diabetic foot, which are suitable for patients with mild to moderate LEAD. They are primarily used to delay the development of the disease and improve the clinical symptoms and quality of life. In some cases, when the above interventions are unavailable or ineffective, some other methods such as spinal cord stimulation or lumber sympathectomy could be considered to relieve pain and to avoid complications.Based on our experience, a multidisciplinary team approach to manage the chronic ischemic pain is vital, since different specialties have different therapeutic options for the treatment of chronic ischemic pain . MoreoveThe management of pain in people with diabetes and CLTI remains a challenge. This is due to the complex pathophysiology of pain in CLTI, limited research base with pharmacological management, varying subjective feelings and severity of individuals, and varying degrees of pain relief for optional treatment approaches. For patients with ischemic pain caused by diabetes-related CLTI, the half-life of analgesia drug is short, so the effect is limited, and appropriate revascularization still remains an effective way to relieve pain and reduce the risk of amputation. Conservative therapy provides temporal pain relief but masks the progress of the ischemic foot and often leads to the disease deterioration. In addition, for ischemic diabetic foot with severe complications, all means may not be useful to avoid occurrence of adverse outcomes. Therefore, it is important for clinicians and patients to deepen their understanding of ischemic pain management and awareness of the possible adverse consequence as early as possible. Simultaneously, a multidisciplinary team approach to mitigate pain and reduce risk factors and comorbidities of CLTI is probably recommended. More efforts should be made to explore to formulate an effective intervention of relieving pain in patients with diabetic lower limb ischemia and to improve their quality of life avoiding the occurrence of adverse consequences.


Entrapments of the intrapelvic portions of the lumbosacral plexus are an important extraspinal cause of sciatica and pudendal neuralgia. They can be treated using Laparoscopic Neuronavigation (LANN), a minimally invasive technique that has set the foundations of an emerging field in Medicine—Neuropelveology. This retrospective-prospective study analyzes the outcomes of 63 patients treated with the LANN technique over a 10 year time period. One year after surgery, 78.3% of patients reported clinically relevant pain reduction, defined as ≥ 50% reduction in Numeric Rating Scale (NRS) score; these results were maintained for a mean follow up of 3.2 years. Preoperative chronic opioid use  was a predictor of poor surgical outcome—clinically relevant pain reduction was observed in only 30.8% in this group of patients, compared to 91.5% in patients not regularly taking opioids preoperatively (p < 0.01). Perioperative complication rate was 20%. Our results indicate that the LANN technique is an effective and reproducible approach to relieve pain secondary to intrapelvic nerve entrapments and that preoperative chronic opioid therapy significantly reduces the likelihood of a successful surgical outcome. This study provides detailed information on perioperative complication and postoperative course, which is essential for patient consenting. As with nerve entrapment syndromes in other parts of the body, intrapelvic nerve entrapments (INEs) are characterized by pain and dysfunction of the lumbosacral nerves’ dermatomes and myotomes, causing pain in the lower limb (sciatica), perineum and gluteal regions, lower urinary tract symptoms, rectovesical tenesmus, dyschezia, vaginal foreign body sensation, dysuria, dyspareunia and/or painful ejaculation7. The LANN technique introduced a systematic and minimally invasive approach to dissect, expose and detrap the intrapelvic nerves, opening the possibility for diagnostic confirmation and treatment of INEs. Additionally, this technique has led to a better understanding of entrapment neuropathies and other causes of dysfunction of the intrapelvic nerves, which resulted in the development a new transitional medical field—Neuropelveology8. Possover et al. proposed a ground-breaking Neuropelveological rationale8, which allows for the diagnosis and management of intrapelvic causes of pudendal neuralgia and sciatica resulting from entrapments at the origin of nerve roots from the sacral foramina down to the sciatic notch and pudendal canal, with success rates close to 80%9. While extremely encouraging, these results are based on narrative case series and their reproducibility still needs to be demonstrated by other groups.INEs were largely unknown before the development of the Laparosocopic Neuronavigation (LANN) technique, by Possover et al.Since late 2009, our team has been offering laparoscopic nerve detrapment procedures using the LANN technique in São Paulo, Brazil. The objective of this study is to report the clinical outcomes of this procedure in our cohort of patients from December 2009 to December 2019.This is a retrospective-prospective analysis of 63 consecutive patients who underwent a LANN detrapment of intrapelvic portions of the lumbosacral plexus from December 2009 to December 2019 at our Neuropelveology center in São Paulo, Brazil.Patients were identified from our surgical database. All the surgical reports within the study period were reviewed and all the patients who underwent LANN detrapment surgery were included. Data was retrospectively extracted from their electronic medical records until 2018, when this research protocol was approved by the research ethics board; data has been prospectively collected since. All data was extracted into a Microsoft Excel database file which began to be prospectively updated in 2018.10. This comprehensive assessment included a full Neuropelveology-oriented history, neurological examination, urodynamic study, pelvic MRI and a diagnostic nerve block.The diagnosis of INEs was based on Neuropelveological assessment, following the standards of the International School of Neuropelveology11. However, it is common for pain relief to deteriorate over time and therefore a higher cut off (50%) is often used for longer-term follow-up studies12.Pain was assessed with a Numeric Rating Scale (NRS), with 0 representing no pain and 10 the worst imaginable pain, at the pre-operative and all subsequent post-operative follow-up visits. Clinically relevant pain reduction was defined as a ≥ 50% reduction in NRS. It is widely accepted in the pain literature that a minimum reduction of 30% or 2-point reduction in a numeric pain scale (from 0–10) defines a clinically meaningful improvement in painThe primary outcome of this study was clinically relevant pain reduction at 1 year follow up. Data from the patient’s most recent follow up was also extracted and analyzed.In addition, the following pre-operative and intra-operative information was collected from the patients’ records: the time of the onset of symptoms, duration and dose of preoperative opioid use, entrapment location and etiology, operative time, intraoperative blood loss and perioperative complications. From this information, the diagnostic lag was calculated and was defined as the time between the onset of symptoms and the time of the LANN detrapment surgery. The operative time was determined from video recordings, defined as the moment the laparoscopic camera was inserted into the abdomen to the moment all ports were removed.Post-operative complications were also extracted from follow-up visits notes. Post-decompression neuralgia (PDN) was defined as pain on the same dermatomes where pain was experienced pre-operatively, with different quality and/or intensity. Any motor deficit within the lumbosacral plexus myotomes developed after surgery was also identified and collected. In the subsequent follow up appointments, the duration of PDN and motor deficits were recorded.Extracted data was put into an MS-Excel database and analyzed in Prism .A chi-squared test was used to assess the proportions of clinically relevant pain reduction rates at 1 year and at final follow-up, to ensure maintenance of pain reduction.To account for patients whose one-year follow up data was not available, three different sub-analyses were performed: patients with missing data excluded, patients with missing data considered a failure  and considering the last follow up data to be the 1-year follow up data .A Komolgorov-Smirnov test was used to assess the normality distribution for NRS scores, which showed that this data did not follow a Gaussian distribution. As such, non-parametric tests were used in our analyses. A paired Wilcoxon’s test was used to compare preoperative and 1-year follow up NRS scores. For this paired test, patients with no 1-year follow up data were excluded from the 1-year analysis. A paired Wilcoxon’s test was also used to compare preoperative NRS score with the NRS score of the last follow up. Finally, to determine if results were unchanged over time, a Wilcoxon’s test was used to compare 1-year NRS scores with the scores from the last follow up.A chi-squared test was used to determine if preoperative chronic opioid use—defined as daily use ≥ 10 mg morphine equivalent for at least 4 months—or if a diagnostic lag of at least two years affected rates of clinically relevant pain reduction. A Mann–Whitney test was used to compare pre-operative NRS homogeneity of both subgroups. Descriptive statistics were used for the remainder of the data.This study was approved by the Research Ethics Board of the Federal University of São Paulo (Protocol # 3.272.139). Consent for collection and storage of images and clinical data for quality improvement, medical education, scientific studies and publications was obtained from all subjects, as a standard practice in surgical consenting process. This consent for authorization of usage of clinical data and images was approved by the REB as part of the ethical analysis. All the proceedings and methods of this study are in accordance with Brazilian research ethics regulations and the Declaration of Helsinki.This study was also registered at the Brazilian Clinical Trials Registry (UTN code: U1111-1261-4910).A total of 63 patients  underwent laparoscopic nerve root decompression during the study inclusion period. The average age of the patients included in this study was 39.9 ± 10.6 years  of patients.Clinically relevant pain reduction, defined as a ≥ 50% improvement in NRS for pain, was 78.3% (47/60) 1 year after surgery . This improvement in pain scores was maintained through the patient’s final follow-up appointment (73.3% (44/60); p = 0.670, Chi-squared test, for one-year versus last follow up), at an average of 3.2 ± 1.8 years. The mean NRS dropped significantly from 8.7 ± 1.8 pre-operatively, to 2.7 ± 2.9 at the 1-year follow-up (p < 0.001), and 3.0 ± 3.2 at final follow-up (p < 0.001). NRS did not significantly differ from the 1 year follow-up to last follow up  time points, suggesting outcomes are maintained over time  or when the result from the last follow up was carried over to one-year follow up .When patients with missing data were excluded, clinically significant pain reduction was achieved on 47/60 (78.3%) of patients. No statistically significant difference in results were observed when patients with missing data were considered failures  consumed ≥ 10 mg morphine equivalents daily, for an average of 18.6 ± 9.6 months. Pre-operative chronic opioid use adversely affected the primary outcome, as the clinically relevant pain reduction was observed in only 30.8% (4/13) in this group of patients, compared to a 91.5% (43/47) in patients not taking opioid on a regular basis (p < 0.01). Preoperative NRS scores were not significantly different between the two subsets of patients—8.6  for non-opiod vs. 9.0  for opioid users (p = 0.4458). The mean time interval between onset of symptoms and surgery was 4.9 ± 4.3 (0.3–15) years for opioid users and 4.6 ± 4.0 (0–15) years for non-opioid users. This difference was not statistically significant (p = 0.7902).The average interval between symptom onset and surgery was 4.73 ± 4.1 years, with patients having undergone an average of 1.1 ± 1.5 years surgical procedures for treatment of their symptoms prior to our LANN detrapment  of patients experienced post-decompression neuralgia, lasting on average 5.7 ± 3.4 (1–12) months. Fourteen (23.3%) patients experienced a post-decompression motor deficit, lasting on average 3.2 ± 3.2 (0.5–12) months.13. However, most literature descriptions of lesions on this plexus refer to its extra-abdominal parts, in the spine or deep gluteal space, while reports of intrapelvic entrapments are traditionally limited to isolated case reports.It is well known that a large portion of the lumbosacral plexus is located intra-abdominally, in the retroperitoneal space2. Therefore, none of the traditional and widely available residency and fellowship programs offers training in the skills set required for the diagnosis and management of INEs.Currently, intrapelvic entrapments are not well understood and rarely considered as a cause of sciatica and pudendal neuralgia. One of the reasons for this is the deep retroperitoneal location of the plexus, in an area that can only be adequately approached by laparoscopy, which provides better lighting, magnification and visualization of this area. Therefore, since the specialists that usually deal with peripheral nerve surgery  are not usually trained in laparoscopy and those specialists who routinely perform advanced laparoscopic procedures  are not familiarized with peripheral nerve surgery, a knowledge gap is created7, opening the doors to accessing the intrapelvic portion of the lumbosacral plexus through a safe and minimally invasive way. This led to the development of a new groundbreaking medical field—Neuropelveology8.In 2004, Possover et al. pioneered the Laparoscopic Neuronavigation (LANN) technique14. The LANN technique was later proposed as a minimally invasive detrapment method to significantly reduce or completely resolve pain secondary to INEs. This surgical intervention follows the same principles of surgeries that have been successfully used in the treatment of other peripheral nerve entrapment syndromes15.The LANN technique was initially developed to standardize nerve-sparing approaches in retroperitoneal dissection during cervical cancer or deeply infiltrating endometriosis surgeries9. Additionally, a study involving 120 patients showed that 65.5% of patients experienced significant improvement in somatic pelvic pain following laparoscopic nerve decompression6. Recently, the same group reported similar outcomes in a series of 213 female patients with lumbosacral entrapment due to neurovascular conflict and/or endometriosis1.In 2009, a series of 134 patients who underwent laparoscopic nerve decompression for refractory anogenital pain showed improvement in VAS scores depending on etiology, with significant decrease in pain achieved in 83% of patients with Alcock’s canal syndrome, 62% of patients with endopelvic lesions, and 78% of patients with endometriosis9 for INEs. It is also the first study with a systematic assessment, as previous reports of INEs are generally narrative case series. In our study, we had a clear time point at one-year follow up for the primary outcome. In addition, this is the first series to report the sustainability of such outcomes at mid to long-term follow up of 3.2 years, on average.This is the first case series in the literature showing the reproducibility of the Neuropelveological approach proposed by Possover et al.17. Prolonged preoperative opioid exposure was the only predictor for poor surgical outcome identified in our cohort; preoperative pain scores and time between onset of symptoms and surgery, two factors we considered would be associated with these results, were homogeneous between chronic opioid users and opioid naïve patients. Such information should influence opioid prescription habits and motivate the use of this medication class only as end-stage therapy. Alternatively, the use of multimodal non-opioid pain management strategies should be promoted in patients with all other forms of chronic pain, as opioids might jeopardize their chances of cure and make them prone to lifelong pain.This is also the first report to show the negative impact chronic opioid use has on long-term outcomes following LANN detrapment of intrapelvic nerves. We show here that chronic opioid use reduces the odds of success of this etiology-oriented treatment from 91.5% to 30.8%. This is of extreme importance as it supports the concept that chronic exposure to opioids may predispose a patient to opioid induced hyperalgesia, thus resulting in a lower pain threshold and thus poor analgesic outcomes16 was developed to diagnose entrapments at the level of Alcock’s Canal and/or at the interligamentous plane. The fact that the most common site of pudendal entrapments in our cohort are the pudendal nerve roots could possibly explain several cases of “atypical pudendal neuralgia” or surgical failures seen in the literature. For the purpose of differential diagnosis, we should raise awareness for the combined symptoms of pudendal pain and sciatica and/or gluteal pain, which could be explained by an INE at the level of the sacral nerve roots.We have also described the different locations of entrapments, which is very important for understanding the dermatomes and myotomes implicated in INEs. It is important to highlight the very small proportion of entrapments at the level of Alcock’s canal (8%) observed in our series. This is very significant, given that “pudendal neuralgia” is often used interchangeably in the literature with “Alcock’s Canal Syndrome”. Also, the most common criteria for diagnosis of pudendal nerve entrapments6.Another important finding in our report is the long diagnostic lag experienced by our patients, who have suffered for 4.7 years and undergone 1.1 previous failed surgeries in an attempt to treat their symptoms. This further illustrates the knowledge gap and lack of awareness of INEs as an extraspinal cause of sciatica and pudendal pain. This data is also consistent with the data reported on European cohorts, in whom an average diagnostic gap of 5.6 years was documented and an average of 4 surgical procedures were conducted before an INE was suspected18. In our patients, the failure rate of LANN decompression was 86% higher when surgery was performed more than 2 years from symptom onset. Although this difference in failure rate did not reach statistical significance, likely due to our limited sample size, it is consistent with the current literature, meaning this likely reflects a reality21.On top of the prolonged suffering, the long diagnostic gap can have other consequences. First, the success rates of detrapment procedures would be adversely affected23; under pressure, healthcare professionals may resort to the use of opioids24. This is of particular importance, as we have shown here that chronic opioid use decreases the chances of a successful surgical outcome.Secondly, lack of awareness of INEs increases the risk of patients undergoing ineffective surgeries which do not address the underlying cause of pain and may cause added harm. Moreover, each surgical attempt further prolongs the treatment delay, as patient and surgeon will need time to assess surgical outcomes. Patients who have been waiting for a long time tend to catastrophizeIn this study we have also systematically assessed the postoperative course. Approximately half of our patients experienced post-decompression neuralgia, which lasted on average about 6 months and almost a quarter of patients experienced a post-decompression motor deficit, lasting approximately 3 months. It is important to make patients aware that post-decompression neuralgia and motor deficits are part of the natural postoperative course, since, if long lasting, they can be misinterpreted as permanent and cause significant distress.In addition, the perioperative complication rate was 20% in our cohort, ranging from nerve injuries to transient bladder symptoms including retention and impaired sensation. For intricate surgery on peripheral nerves, such as LANN detrapment, this complication rate is within the acceptable range, but discussing these risks with patients is essential for appropriate preoperative counselling and consenting.13 results, as well as the similarity of the outcomes with surgical treatment of other nerve entrapment syndromes suggests that our results can be extrapolated to a larger population.This current study is limited by the relatively small cohort, retrospective design and the use of NRS as the singular outcome measure. However, the consistency with Possover et al.’sFuture studies assessing the impact of laparoscopic nerve detrapment surgery on different variables, such as sexual function, quality of pain, bowel/bladder dysfunction, and psychosocial components of chronic pain, will help to create a more robust understanding of the outcomes of this approach. Additionally, following patients for a longer post-operatively will result in further understanding of the maintenance of the effects of surgery and the future need for additional pain management medications or procedures.Nevertheless, our results validate the Neuropelveology approach to diagnose and treat INEs and highlight the importance of raising awareness of the risk of non-specific pain management opioids, which significantly reduces the likelihood of a successful surgical outcome.


This study aimed to compare the analgesic effectiveness of virtual reality vs. topical anesthesia gel during the administration of local anesthesia (injections to numb the gums) in adult dental patients; as well as to determine which approach is preferred by the patients. Twenty-one adult patients received dental anesthetic injections bilaterally for their maxillary premolars area. We predicted that VR would be more effective than a topical anesthetic gel at reducing pain during injections into the gums. Using a within subject design, each patient received two injections during a single dental visit. Pain was measured after each injection. One side was of the mouth was injected under the influence of the topical anesthesia (TA) 20% benzocaine. The other side of the mouth was injected when the patient was in virtual reality (VR) watching an animated movie using an Oculus Quest® helmet to distract them during the other injection, treatment order randomized. Immediately after each injection, the patients were directed to rate their pain experience using the Wong-Baker Faces Pain-rating Scale (W-BFPS), and to choose which delivery system they preferred. Heart rates were recorded prior to and after the injections using a finger pulse oximeter. Participants reported the predicted pattern of a lower W-PFPS score (less pain intensity) during needle injection while in VR than the injection with topical anesthesia gel, however, the difference was not statistically significant. A statistically significant majority of the participants (p = 0.021) preferred VR to TA. No statistically significant difference heart rate during VR vs. TA was found. Although dental patients reported less pain during VR distraction vs. topical gel anesthetic, the difference was not significant. A statistically significant majority of patients preferred virtual reality over topical anesthesia during their future injections. However, no significant difference in heart rate was found. Managing dental fear is considered an important issue in dental practice3. Many people who have needle phobia avoid or postpone treatments owing to their fear and anxiety, mainly from dental anesthesia needle pain5. Rather than attending the recommended regular checkups, patients with dental fear usually only go to the dentist when they suffer pain ; this increases the chance that their visit to the dentist will cause pain6. Moreover, unpleasant early dental experiences can affect patients’ perception of healthcare, can increase pain and suffering during subsequent medical visits, and can reduce preventative healthcare, in turn affecting lifelong health7.Needle phobia is one of the most common phobic conditions. In one recent study, 67% of young pediatric patients had high anxiety before their vaccination10. Pain perception has a large psychological component in that the amount of attention directed to the noxious stimuli modulates the perceived pain12. Recently there is growing evidence that virtual reality (VR) can serve as a powerful distraction tool for pain and anxiety control. VR has unique characteristics that makes it a very effective distractor13. VR is able to engage different senses simultaneously and induce a sense of presence in the virtual environments ; thus, efficiently diverting attention from painful stimuli14. The use of immersive VR to distract dental fears patients was first introduced by Hoffman et al. in 200115.Distraction is proving to be an essential technique for reducing pain during short invasive medical proceduresAlthough previous studies have tested the efficacy of VR as an adjunctive non-pharmacologic analgesic during dental treatments, to date, no study has evaluated its effect on pain perception as a replacement for topical anesthesia to help reduce pain during injection of a local anesthetic. In this study, this will be evaluated as a step toward virtual dental analgesia.The aims of the study are to compare the analgesic effectiveness of virtual reality (VR) vs. topical anesthesia (TA) gel during administration of local anesthesia in adult dental patients, and to determine which approach the patients preferred to reduce pain of dental injections.Using a within subject design, each patient received two injections during a single dental visit. We predicted that (1) VR would be more effective than a topical anesthetic gel at reducing pain during dental anesthesia injections into the gums, (2) patients would prefer VR compared to gel, and (3) heart rate would be lower during the VR condition than during the topical anesthesia gel condition.This study was performed in accordance with the Declaration of Helsinki. Twenty-one adult participants visiting the restorative dentistry department in the dental hospital participated in the study, with an age range from 22 to 59 years. The procedures were explained to the participants in detail and an informed written consent form was signed by each participant. The study was approved by the Ethics Committee in the Institutional Review Board (IRB) no. RC/IRB/2019/321 from the Research Center at Riyadh Elm University. The research is also registered in the website of ClinicalTrials.gov with NCT 04919421, date 09/06/2021. The full trial protocol could be accessed through the same website as well.topical anesthesia gel before to help numb the gums before one injection, or to go into virtual reality during the other injection (treatment order randomized). All dental procedures were done by one person, a senior dentist experienced in administering dental anesthesia. Since it was a within-subject, split-mouth design, each participant served as his/her own control.This study was conducted according to the design of split-mouth randomized controlled single-blinded trials . Using a within subject design, each patient received two injections during a single dental visit. Patients received on injection into the gums of the upper premolars on one side; and then the other injection on the contralateral side of the mouth. Each participant was randomly allocated to receive Sample power was calculated using the G-Power sample power calculator . Given the split mouth study design, an effect size of 0.75 (large effect size) was assumed and for a power of 0.95, the total number of participants was determined as 21.Class I of the American Society of Anesthesiologists (ASA) as approved by the ASA House of Delegates on October 15, 2014; aged 18 and above, both genders.Participants are in good general health, take no medications, and have no contraindications to the use of local anesthetic.The ability to understand oral and written instructions.12. All the time periods were calculated using Clock App timer available on an iPhone device. The injection of anesthetic solution was performed according to the standard technique mentioned below. Directly after the injection, the pulse rate was recorded a second time.For each participant, the heart rate was recorded immediately before and after the injection using an FDA approved pulse oximeter . The injection site was dried and isolated using a cotton roll and a small quantity of the topical anesthesia Iolite 20% benzocaine  anesthetic gel was applied using the end of an applicator stick directly at the site of penetration for 15 s and then left for 2 min to ensure effectiveness® (Facebook Inc. USA). The device was loaded with the animated short movie ‘Henry’  and then properly adjusted around the patient’s head and in front of her/his eyes. The volume level was controlled and interpupillary distance (IPD) was adjusted by each participant after providing brief instructions. The movie was played for some time prior to administration of the injection to enable the participant to get involved with the scene. The next step comprised of guiding the patients to turn their heads and adapt with the dentist’s instructions while watching the movie. The injection of anesthetic solution was performed according to the standard technique mentioned below while the participants continued watching the VR movie. Directly after the injection, the pulse rate was recorded a second time.For each participant, the heart rate was recorded immediately before and after the injection using an FDA approved pulse oximeter. The virtual reality stand-alone headset used in the study was the 128 GB Oculus Quest, USA); , delivered in cartridges using a 27—gauge short needle . A sterile non-aspirating syringe was used, as recommended for infiltration anesthesia for maxillary teeth16.The injection was made with 1.8 ml Xylocaine 20 mg/ml , the participants were asked to evaluate the degree of pain (primary outcome) that they experienced using the Wong-Baker Faces Pain-rating Scale (W-BFPS), a tool to measure the intensity of pain comprising a scale from 0 to 10. The patient will select a number based on the intensity of the pain, "0" means no pain, "10" means extremely severe pain. Official permission was issued from the Wong-Baker FACES Foundation.Additionally, each participant was also asked to state his/her preference of delivery system (primary outcome) for future injections. And heart rate will be measured for the participants before and after each injection (primary outcome), using an FDA approved pulse oximeter .To reduce the risk of bias, the following were considered:• Both procedures were coded and blinded to the one who did the analysis.• Both types of dental procedures were performed by one person, a senior dentist experienced in administering dental anesthesia to avoid an inter-operator variability influence.• Special attention was given to keep the syringe out of their line of sight.injection shot, pain, and hurt) were not used to avoid increasing stress or fears.• Regarding communication with the participants, the words , non-parametric tests were used to analyze differences in W-BFPS. The normality of the heart rates observed was calculated and was observed to be within acceptable limits of Kurtosis and Skew. Therefore, parametric tests were used to analyze differences in heart rate.t test was used to compare the heart rates of the individuals between the two methods. The Spearman’s correlation was used to check the association between W-BFPS and heart rate for each procedure. All tests were performed at p < 0.05.The Wilcoxon Sign rank test was used to compare the W-BFPS between the two methods. The paired The sample was comprised of 21 participants  aged between 25 to 59 years of age. The mean ages for females and males was 35.4 and 34.5 respectively, with no significant difference (p = 0.847).The patient’s experience of pain with each group was measured using Wong-Baker Faces Pain-rating Scale (W-BFPS). The Wilcoxon Sign Rank test showed that while 10 of the 21 participants had a higher W-BFPS with TA when compared to VR, 5 of the 21 reported a worse experience with VR when compared to TA. There were six individuals who reported the same experience with both procedures  reported that they preferred the VR to Topical Anesthesia  with VR than with topical anesthesia gel, but the difference between VR and TA was not statistically significant. A significant majority of the participants preferred VR to TA. But contrary to predictions, there was no statistically significant difference heart rate during VR vs. TA.In the last two decades, there has been increasing interest in the application of virtual reality during dental treatments. The current research advances a step forward from using virtual reality as an analgesic adjunctive tool to using it as an anesthetic adjunctive tool. The study provides some insights for future implementation as it is the first of its kind that tested the effectiveness of virtual reality distraction as a psychological tool to control pain while receiving dental local anesthesia.17. Studies comparing the ability of interactive and non-interactive VR systems in pain management, found that interactive distraction was more effective18. This observation supports the view that engaging attentional resources in tasks can interfere with pain processing19. Audio, visual, and kinesthetic sensory modalities are all combined in VR, and based on how immersive the stimuli are, a person’s attention will be more or less drained21. In general, manipulations designed to increase the patients illusion of “being there’ in the virtual world, typically also increased how much VR reduces pain.Distracting the patient from an unpleasant stimulus may result in decreased pain perception® has several advanced features, of which rotational motion tracking is one of them. This feature is, however, a disadvantage when being used in the dental operatory, if a game is being played while the patient is being treated, as they will not be able to sit still as the virtual reality might impede the positioning of the head, rotation, visual field, and change of direction. Therefore, an animated movie was chosen to be played, instead of games, to ensure patient stillness, and also to overcome any language barrier among the multi-national participants. Atzori et al.22 used a custom VR software that allowed participants to use their mouse to interact with the virtual world (mouse tracking), without moving their heads (no head tracking). Although VR movies worked well in the current study, interactive immersive VR is recommended for more painful dental procedures.The Oculus QuestThe patient’s pain experience with each group was measured using Wong-Baker faces pain-rating scale (W-BFPS). Although the predicted pattern was observed, the differences were however not statistically significant.24, and 74% of patients reported to prefer wearing video glasses if they were to receive another dental filling25.When patients were asked which method they preferred, a significant majority (71.4%) favored VR over TA and is indicative of the positive experience patients had with VR. This finding was concurrent with the results of other experimental studies where three-quarters of the patients wished to use video glasses when subjected to future cold pressor testsIn the present study, the difference between the heart rate before and after treatment was not statistically significant.26. In that previous study, approximately two-thirds of the study population reported that they preferred the VR distraction method during SRP procedures, one-third preferred to watch the movie and only one patient preferred no distraction at all. Not only did patients prefer interacting with the VR environment and report lower levels of pain, but also had significantly lower Pulse Rate and Blood Pressure measurements during the VR experience.A study which examined the efficacy of VR distraction on pain control during periodontal scaling and root planning procedures (SRP) showed that it was an effective tool27 reported that the use of virtual reality glasses is an effective tool for improving behavior and reducing pain perception during the dental treatment of children. Children who used VR eye-glasses behaved better during removal of caries and showed lower pain perception during restoration. Another recent systemic review and meta-analysis28, about use of virtual reality for the management of anxiety and pain in dental treatments concluded that VR is a useful tool to reduce pain in children undergoing dental treatment, while there was no significant effect on dental anxiety.A meta-analysis study10.Limitations. This study had a number of limitations to take into consideration. The sample size of the participants was relatively small, further studies with a larger sample size are needed. Additionally, the size of the headset was a bit big and not convenient to perform dental treatment. Smaller headsets have recently become commercially available. Although fear is an important mediating variable, fear was not measured in the current study. Similarly, future studies should measure how much fun patients have during the procedure22, which could make patients more willing to visit their dentist more often. The current results add to growing evidence for the effectiveness of immersive virtual reality as an adjunctive pain control technique. Additional research and development is recommended.Despite these limitations, the current study is the first to measure the use of VR distraction to reduce patients discomfort during needle injections. Through this study we can conclude that the effectiveness of virtual reality in reducing pain caused by dental injections is comparable with that of topical anesthesia. Additionally, a significant majority of patients preferred virtual reality over topical anesthesia during their future injections. Previous studies have shown that VR makes painful stimuli more fun


Currently, general measurements and evaluations of the quality of recovery are difficult because no adequate measuring tools are available. Therefore, there is an urgent need for a universal tool that assesses patient-relevant criteria—postoperative pain, state of health, and somatic parameters. For this purpose, a pain and state of health inventory  in German) has been developed. In this study, we describe its development and validation. The development phase was led by an expert panel and was divided into three subphases: determining the conceptual structure, testing the first editions, and adjusting the inventory for a finalized edition. For the purpose of validation, the PHI was filled in by 132 patients who have undergone total knee replacement and was analyzed using principal component analysis. Construct validity was tested by correlating the items with validated questionnaires. The results showed that the inventory can test pain, state of health, and somatic parameters with great construct validity. Furthermore, the inventory is accepted by patients, map changes, and supports to initiate adequate treatment. In conclusion, the PHI is a universal tool that can be used to assess the quality of recovery in the perioperative setting and allow immediate intervention. Evaluating the quality of recovery in the perioperative setting is considered very important to ensure the best possible treatment for patients. Therefore, many studies have focused on the quality of recovery ,2. HowevGenerally, evaluating the quality of recovery is important not only because it has a direct impact on the immediate treatment quality, but also because it prevents negative long-term effects, such as chronic pain or morbidity. Postoperative pain is a relevant marker of postoperative healing, and severe postoperative pain is a risk factor for the development of chronic pain ,9. It shThe relevant outcomes for patients are pain ,15, statOne reason for the inadequate postoperative pain treatment is that no suitable tool is currently available to perform an appropriate pain diagnosis and assess the state of health within the perioperative setting . AlthougThe aim of this study is to demonstrate the development of the PHI and validate it as a general tool designed for the perioperative setting. In this context, in this study, we investigated whether the PHI is widely accepted, easy to understand, sensitive to changes within the perioperative setting, and of general use in everyday clinical practice.In this study, we focus on the development and validation of the PHI. The first part of this article describes the development of the PHI, and the second part describes the validation of its finalized edition.The development process of the PHI consisted of three main steps: (i) determining the conceptual structure formulating corresponding items, (ii) testing the first editions, and (iii) adjusting the inventory for a finalized edition. Both the conceptual structure and items were designed by experts in the perioperative setting and were validated with external criteria. The consulted experts were specialists in orthopedics and trauma surgery, and specialists in psychological pain psychotherapy, both with several years of experience in operative and postoperative management. The strategy to base the items on expert rating was chosen to facilitate a discussion about the included items and to adjust the inventory based on patients’ suggestions and recommendations. The items are arranged into different subgroups: pain, state of health , and somatic parameters. To cover the whole perioperative setting, the PHI consists of an entry version, which is filled out preoperatively, and a progress version, which is filled out postoperatively. Hence, the version of the inventory indicates the occasion the patient receives the inventory. However, all patients always receive both versions.The conceptual structure consists of different subsections: pain, state of health , and somatic parameters.For pre- and postoperative pain, the specification of pain perception, including intensity, location, duration, and frequency, is considered to be particularly relevant . For thiTo assess the state of health , relevant items were formulated with the expert panel by considering commonly used tools. Generally, most questionnaires pertaining to the postoperative emotional state deal with anxiety and depression . MeasureSomatic parameters are an important aspect for postoperative recovery for different surgeries ,48,49,50To capture changes in the perioperative setting, it was planned to design an inventory that would be used preoperatively to record the patient’s preoperative state, and also postoperatively to facilitate patient monitoring. The aim is to enable the application of the inventory based on requirements and needs of the hospital ward, so that the inventory could be applied daily postoperatively or on certain days postoperatively.To validate the corresponding items, the PHI was supplemented with the Pain Perception Scale, Hospital Anxiety and Depression Scale, German Version , SensitiThe second edition was again tested at the German University Medical Center Lübeck on 111 patients  who have undergone surgery. Special attention was again paid to truly include the patients’ perspectives. Therefore, patients were encouraged to suggest relevant items and raise concerns or write comments. As in the first edition, patients received additional questions to raise concerns and were asked in a personal interview about the individual items and if they missed relevant items. The results showed that the patients were content with the included subsections and items. They confirmed that their recovery criteria were covered in the PHI. On the basis of the comments made by the patients and the results obtained from the external observation, the PHI was adjusted and finalized, followed by a further validation step see . One greBased on the results from the second preliminary study, a finalized version was created. The items of the finalized inventory were structured as follows . The invTo validate the PHI, it was tested at the Schoen Clinic Hamburg Eilbek, a German hospital clinic.Subjects were considered eligible for participation if they were 18 years of age or older and if they had undergone total knee replacement (TKR) as a result of knee osteoarthritis. Those who were cognitively impaired, had insufficient command of the German language, suffered from any mental disorders (according to ICD-10) which require psychiatric medication, consumed any consciousness-impairing substances , or suffered from any pain requiring special causative medical treatment  were excluded. However, due to the circumstance that depression and pain are co-prevalent and the population should not be unnecessarily limited, patients with the diagnosis F45.41  were not excluded. All patients participated voluntarily and provided written consent.For recruitment, the patients were first screened for eligibility and then received comprehensive information about the study objectives. Those who agreed to participate and provided written consent were asked to fill in a battery of questionnaires. The first part (entry version) of the PHI was handed to the participants one day prior to the surgery, and the second part (progress version) was handed to them five days after the surgery. All the participants were asked to report their age, gender, marital status, and employment status. For the purpose of validation, von Korff et al.’s questionnaire for grading the severity of pain  was asseFirst, representativeness regarding demographic characteristics of the sample was determined. Second, acceptance was assessed by evaluating the answering behavior and examining the missing values. Third, the distribution of values was analyzed using descriptive statistics. Next, sensitivity to changes was analyzed using univariate analyses of variance (ANOVAs) for continuous variables and chi-square test for categorical variables. Validity was analyzed using Pearson’s correlation, and the dimension of emotional state was evaluated using principal component analysis (PCA). For the PCA, Varimax rotation and Kaiser normalization were applied. Missing data were deleted list-wise to avoid data distortions. Extraction and retention of factors were based on a scree plot and an eigenvalue greater than 1.0 ,62. The η2 was calculated as an indicator of the effect size. The cutoffs of partial η2 values of 0.01, 0.06, and 0.14 were interpreted as small, medium, and large effects, respectively [All analyses were performed using IBM SPSS Statistics version 25.0 . The significance level for all tests was set at α = 0.05 (two-tailed). For correlations, cutoff values were applied to indicate the strength and direction of correlation. Correlations were interpreted using Cohen’s benchmark and categorized as small (|r| = 0.10), medium (|r| = 0.30), or large (|r| = 0.50) . For ANOectively . The appectively .A total of 135 patients who have undergone TKR at the Center for Orthopedics and Trauma Surgery in Schoen Clinic Hamburg Eilbek, Germany, from October 2015 to March 2019, agreed to participate in this study. Among these, 132 filled in at least one version of the inventory and were, therefore, included in the analysis. These participants are considered representative of those who have undergone TKR from among the German population in terms of age, gender, marital status, and employment status .Overall, the results showed that the inventory was widely well accepted. Not many patients made use of the possibility to comment on the inventory, but declared that they felt well represented. Preoperatively, 91% of the patients responded to the item regarding prominent pain. Moreover, all of those who indicated that they are experiencing pain indicated the painful area preoperatively, and 93% provided information about the painful area postoperatively. Overall, 91% of the patients provided information about the painful area, and 90–92% responded to items pertaining to the emotional state. Information regarding the general state of health was provided by 92% of the patients preoperatively and 94% postoperatively. Furthermore, postoperatively, the patients were asked about their somatic parameters, including their diets and mobility, and whether they were satisfied with them. In total, 86% of the patients responded to items pertaining to somatic parameters, and 87% indicated whether they were satisfied with the diet they received or whether they would have tolerated more or less. In addition, 94% of the patients provided information regarding their mobility, and 93% indicated whether they were satisfied with their amount of mobility or whether they could have moved more or less.In total, 72 patients (55%) stated that they had no other pain besides the preoperative knee pain, whereas 22 patients (17%) pointed out more than one painful area preoperatively besides knee pain. Postoperatively, 87 patients (66%) denied additional pain, 25 patients (19%) reported one additional painful area, and 11 patients (8%) reported several additional painful areas. As all the patients indicated that they were experiencing knee pain related to the upcoming surgery, the additional painful areas were further analyzed. In total, 36 patients (32%) experienced pain in one additional area pre- and postoperatively, 17 patients (15%) experienced additional pain preoperatively but not postoperatively, seven patients (6%) experienced no additional pain preoperatively but some pain postoperatively, and 51 patients (46%) experienced no additional pain either pre- or postoperatively.2(1) = 36.41, p < 0.001, φ = 0.57. Both pre- and postoperatively, the most prominent painful areas besides the knee were the back, shoulders, arms, and legs. In total, 27 patients experienced back pain preoperatively and 15 patients experienced the same pain postoperatively. Moreover, 19 patients experienced shoulder and arm pain preoperatively and 10 patients experienced the same pain postoperatively. Finally, 18 patients experienced leg pain preoperatively and 10 patients experienced the same pain postoperatively.Patients who reported additional pain besides knee pain preoperatively were more than those who reported the same postoperatively: χIQR = 3–5), whereas the maximum pain was NRS = 8 (IQR = 8–9). The median average postoperative score was found to be NRS = 1.97 (IQR = 2–3). All patients reported experiencing knee pain several times a day. In total, 74% of them stated that they have been experiencing knee pain several times a day for more than a year, 15% have been experiencing knee pain for more than 6 months, 8% have been experiencing knee pain for 3–6 months, and only 1% has been experiencing knee pain for less than 3 months.The median of the average preoperative knee pain score was found to be NRS = 4 (interquartile range = p < 0.001), indicating that the correlations between items were sufficiently large to perform a PCA. Only factors with eigenvalues of ≥1.0 were considered [The PCA revealed particular factor loadings, and the KMO measure of sampling adequacy was found to be 0.81, representing a relatively favorable factor analysis. Moreover, Bartlett’s test of sphericity was found to be significant .The item pertaining to pain was found to correlate significantly with that in von Korff et al.’s questionnaire , anxiety , tiredness , numbness/dizziness , weakness , and irritation , as well as the general mood . Similarly, obstructive self-instructions were found to exhibit moderately to strongly significant correlations postoperatively with feelings of sadness , anxiety , tiredness , numbness/dizziness , weakness , and irritation . Moreover, “sad” was found to correlate with depression from PHQ-4 preoperatively  and postoperatively , whereas “anxious” was found to correlate with general anxiety from PHQ-4 preoperatively  and postoperatively .The emotional state was found to correlate significantly with pain-related obstructive self-instructions derived from FSS . In particular, obstructive self-instructions  were found to exhibit moderately to strongly significant correlations preoperatively with feelings of sadness  of health, and the form of exercise was found to correlate significantly with the observer rating  of exercise.The general state of health was found to correlate significantly with the observer rating  and are also more emotionally stable. This is in line with previous research findings, which have indicated that an upcoming surgery entails psychological stress for patients preoperatively ,73 but tBesides its primary aim of developing an inventory for assessing patient-relevant outcomes to evaluate the quality of recovery, the present study provides an inventory that helps assess whether an additional intervention related to pain treatment, emotional support, or changes in mobilization or diet is necessary and should be introduced. This is considered highly relevant because of the known lack of adequate postoperative pain treatment . The difGiven the chosen target group, the average age in this study was relatively high (68 years). The age is a limiting factor because the results cannot without further studies be generalized to all age groups. However, for the investigated patient group, the age is representative. Moreover, for the purpose of the final validation, only patients who underwent TKR were considered, whereas for previous validation general surgery patients were considered. Furthermore, anesthesia-relevant effects are not included in the inventory, but might also be relevant for further treatment. One limitation of the inventory is that only the average pain is asked, but is not differentiated between pain at rest and pain at movement. Therefore, for a more detailed assessment, in the most recent edition of the inventory items concerning pain at rest and pain at movement were added.https://clinicaltrials.gov/ct2/show/NCT04528537?term=quality+of+recovery&cond=quality+of+recovery&draw=2&rank=3, accessed on 29 March 2021).To generalize the results to other types of surgery, the PHI should be implemented for different types of surgery and age groups and the results should be confirmed using confirmatory factor analysis. Including the results obtained with other types of surgery can help establish and accurately evaluate the differences between the types of surgery and quality standards. Another planned research step is to merge the PHI with a questionnaire which focuses primarily on negative clinical effects of the anesthesia . A study is currently ongoing on this instrument (Fischer, M., Zöllner, C. The PHI is a general tool that focuses on a detailed evaluation of pain and the state of health within the perioperative setting. It allows the assessment of the quality of recovery and helps guide immediate adequate interdisciplinary postoperative pain treatment. Therefore, it is recommended to apply the PHI in the perioperative setting because it is easy to understand, is well accepted, maps changes in the perioperative setting, and includes patient-relevant parameters.