Significant correlations were found between helpfulness ratings and sociodemographic data indicating that perceived treatment helpfulness was influenced by patient-related factors. Importantly, the degree of pain-related improvements was affected by the patients’ perceived treatment helpfulness. In conclusion, patients’ perceived treatment helpfulness differs significantly between treatment modalities and corresponds to treatment outcome.Multidisciplinary pain management programs (MPMP) for patients suffering from chronic back pain include a variety of treatment modalities. The patients’ perceived helpfulness of these treatment modalities remains unclear. The aims of this prospective observational cohort study were to assess (i) the patients’ perceived helpfulness of different treatment modalities, (ii) the influence of sociodemographic characteristics on the patient’s perspective and (iii) whether treatment outcomes are affected by helpfulness ratings. Treatment modalities of this three-week MPMP consisted of individual physiotherapy, group-based physiotherapy, relaxation therapy, aquatic therapy, back education, medical training therapy, biofeedback, psychological pain therapy and music therapy. The study comprised 395 patients. The main outcome was the patients’ perceived treatment helpfulness at the end of the program measured by a self-reported questionnaire ranging from 1  to 6 (extremely helpful). Secondary outcomes were treatment effects on pain, pain related disability, functional ability and level of depressive symptoms measured by self-reported questionnaires . A total of 276 patients  were available for overall analysis. Multivariate-analysis-of-variance- (MANOVA-) related results revealed that perceived treatment helpfulness (range 1–6) differed significantly between treatment modalities: individual physiotherapy (M = 5.00), group-based physiotherapy (M = 4.87), relaxation therapy (M = 4.6), aquatic therapy (M = 4.54), back education (M = 4.43), medical training therapy (M = 3.38), biofeedback (M = 3.31), psychological pain therapy (M = 3.15), music therapy (M = 3.02). Pain, pain related disability and levels of depressive symptoms significantly improved after the program ( As early as 30 years ago, the Swedish orthopedic surgeon Dr. Alf Nachemson described education, exercise and encouragement as the three essential pillars of non-surgical treatment for localized back pain . Indeed,To achieve these goals a prospective, observational cohort study was performed. The study was part of clinical care and conducted in accordance with the local ethics committee of the Medical Faculty of the University of Heidelberg and the Declaration of Helsinki and was approved by the institutional review board (257/2002).A total of 395 patients with chronic non-specific localized musculoskeletal back pain completed a three-week MPMP as described below. All patients were referred to our clinic for biopsychosocial pain management due to failure of conventional treatment approaches including standard care and non-multidisciplinary interventions. Participating in the MPMP was part of clinical care. Prior to program and study enrolment, all patients were examined by an experienced physician of the pain department and eligible patients provided written informed consent. Data were obtained using paper-and-pencil self-administered questionnaires without assistance of study personnel at the beginning  and at the end of the program . From the 395 patients that had agreed to voluntarily provide self-reported data during clinical care, 331 fully completed all questionnaires at the beginning of the program. At the end of the program, 276 patients were available who had filled in the questionnaires completely at both T0 and T1.Patients between 18 and 65 years suffering from chronic non-specific and localized back pain (>6 weeks) were included. Moreover, physical abilities allowing for daily exercises  and adequate knowledge of the German language were required to participate in this study. If necessary, physical capacity was evaluated by a cardiologist in outpatient care prior to enrollment.Patients with specific back pain including pain following fractures, cancer, systemic inflammatory diseases or infections  as well as rheumatic diseases and severe degenerative alterations were excluded. Structural changes of the spine with acute clinical symptoms such as spinal stenosis or spondylolisthesis resulting in spinal claudication as well as disc herniation causing corresponding radicular pain also led to exclusion of this study. Furthermore, patients with multiple pain locations  and serious medical conditions  were not included. Ongoing litigation or receiving worker’s compensation benefits related to their pain were also considered exclusion criteria.The pain management program was an outpatient program offered at the multidisciplinary pain center of the Clinic for Orthopedics and Trauma Surgery at Heidelberg University Hospital. It consisted of three weeks of multidisciplinary treatment five days per week, five hours per day, resulting in a total of 75 treatment hours. During the multidisciplinary treatment (5 h/d) patients stayed at the pain center and were released to their private accommodation after completing their daily schedule. Treatment costs were covered by internal university funding. Integrating physical exercises, patient education and psychosocial interventions the multidisciplinary program addressed the biological, social and psychological factors of pain. By promoting physical activity and reconditioning, reducing maladaptive cognitions and improving emotional functioning as well as by building/improving coping strategies, the program aimed at restoring physical and psychosocial functioning to decrease the impact of pain on daily activities. In general, the entire multidisciplinary team used a cognitive-behavioral and psychodynamic approach to establish and increase the patients’ understanding of the nature of pain. Team meetings were held once per week to evaluate the patients’ progress and to discuss how to proceed with individual psychosocial conflicts. Treatments were delivered in groups (max. 12 patients) as well as in individual sessions (one-on-one) and are described in detail below.At study entry, a comprehensive physical examination was performed by the supervising physiotherapist to assess the patients’ individual physical performance including muscle strength, flexibility and endurance. Based on physical abilities individual therapeutic goals were defined in agreement with the patient and addressed in individually- and group-delivered physiotherapy sessions. An operant behavioral approach was chosen to encourage functional improvements. Group sessions included aerobic and resistance exercises. In particular, the patients participated in daily sessions of Nordic walking (1 h), core stability and stretching exercises (1 h) and in indoor/outdoor sports sessions with the opportunity for recreational activities . Individual physiotherapy sessions (2 × 30 min/week) addressed the patients’ musculoskeletal discomfort by using patient-tailored stretching, strengthening and relaxation techniques supervised by a professional physiotherapist with experience in the treatment of CBP.Daily sessions (45 min of aquatic therapy with subsequent voluntary swimming (15 min) in a heated therapy pool were part of the program. Under the supervision of a qualified aquatic therapist, the patients performed active aquatic exercises including water aerobics and aqua running to improve physical functioning.To increase muscular strength and endurance, the patients performed device-assisted exercises  in the hospital’s gym. Following a detailed initial instruction for appropriate use of the medical training devices and individual adjustment recommendations by a specialized physiotherapist, patients trained autonomously. At all times, the physiotherapist in charge was present to give assistance when necessary.To improve body awareness and develop strategies of tension management, electromyogram-based biofeedback training was performed once a week for 45 min. Muscle tension was assessed at the neck and lower back with surface electrodes measuring muscle activity. Acoustic and visual feedback was provided and relaxation techniques to reduce muscle tension were applied. The relationship between muscle tension, stress and pain was explained and patients were asked to practice the instructed relaxation techniques at home. Moreover, we encouraged the patients to develop their own strategies to reduce tension.Besides patient education on basic spine anatomy and function, back education (2 h/week) included exercises to increase strength and endurance of essential core stability muscles such as the transversus abdominis, multifidus and pelvic floor.Group relaxation sessions took place twice a week for one hour each. Relaxation therapy included Jacobson’s progressive muscle relaxation and autogenic training and was conducted by a qualified psychologist.Patients participated in group music therapy once a week for one hour. Supervised by an approved music therapist, active music therapy was performed using instruments and voices.Psychological pain therapy consisted of group and individually-delivered interventions. Important elements of group sessions (1.5 h/week) were psychoeducational training including behavioral therapeutic techniques, problem solving strategies and stress management. One-on-one psychological sessions (1 h/week) aimed at identifying and addressing the patient’s individual psychosocial factors and emotional conflicts contributing to the development and persistence of CBP.To ensure adequate medical supervision, appointments with the attending physicians  were scheduled twice a week for one hour. Besides physical examinations at study entry and at end of the program the physicians monitored drug usage and managed potential medical issues occurring during the three weeks of treatment. In general, patients were encouraged to reduce/withdraw their pain medication under medical supervision. None of the patients needed intravenous or intramuscular analgesics either at study entry or during the program. When necessary, non-opioid analgesics, including nonsteroidal anti-inflammatory drugs, Metamizole or Acetaminophen, were prescribed. Patients using oral Opioids at study entry were encouraged to reduce the opioid intake under medical supervision. Additional opioids were not prescribed.After completing the program, patients were discharged without further interventions by the pain department. They were allowed to contact the referring physician but were advised to independently cope with future pain episodes applying the acquired knowledge and techniques without seeking immediate medical attention. Health care utilization following the end of the program was not monitored.Sociodemographic data were recorded prior to the program (T0) using the self-reported standardized questionnaire of the German Pain Society  and inclTo explore which treatments of the MPMP  are perceived as helpful patients assessed the different treatments regarding pain improvement using a self-reported questionnaire at the end (T1) of the program. They evaluated how helpful respective treatments have been in reducing their pain on a scale from 1 to 6 . Treatments were considered helpful when rated ≥ 4 (= moderately helpful).To detect treatment effects after three weeks, analgesic intake, pain intensities , pain-induced disability (Pain Disability Index = PDI), functional capacity  as well as depression and depressive disorder  were monitored throughout the study at both T0 and T1.Pain intensity was rated on an 11-point numeric rating scale (NRS 0–10) with terms describing pain severity extremes . Patients rated their current as well as average, worst and least pain within the last week. In current literature, the self-reported NRS is considered a reliable measure to assess pain intensities whereas a 1.5 to 2-point minimum detectable change (MDC) seems to be necessary for clinical meaningfulness ,21,22,23α was 0.85, and for factor 2, Cronbach’s α was 0.70 [The German version of the Pain Disability Index (PDI) was used to measure pain-related disability ,25,26. Twas 0.70  The miniwas 0.70 . Therefowas 0.70 .Back function was assessed using the Hannover Functional Ability Questionnaire for measuring back-pain-related functional status (FFbH-R) . The FFbα), and the one-week, two-week and three-month test-retest reliability were good . Factorial, discriminant and convergent validity has been evaluated in a variety of studies  [To evaluate the current level of depressive symptoms, the German equivalent of the Center for Epidemiologic Studies Depression Scale (ADS-L)  was appl points) .® Statistics 24.0  for Microsoft® Windows V.10  with a significance level of 5% (α = 0.05) and a confidence interval (CI) set to 95%. Only data from patients completing the questionnaires at both T0 and T1 were used. As a first step, an explorative data analysis for all variables was carried out. Normal distributions for subsequent correlation analyses and t-tests were assessed by the Kolmogorov–Smirnov and the Shapiro–Wilk test. The homogeneity of variance according to MANOVA-related calculations was verified by the Levenne test.All analyses were performed using IBM SPSSt-tests or non-parametric Wilcoxon signed rank tests were used to detect significant changes in NRS, FFbH-R, PDI and ADS-L after completing the program. For variables that significantly decreased or increased, differences between T0 and T1 were calculated as delta values (Δ) in the second step. Except for Δ FFbH-R (as change in percent), a positive assignment for improvements was achieved by subtracting T1 from T0 values . Finally, using the delta values as dependent variables, one-way MANOVA with Bonferroni adjustments was conducted. If the homogeneity of variance was violated, Kruskal–Wallis tests were used instead. CIs and effect sizes  are provided by MANOVA-related calculations. As presented in 2 was calculated using an online tool [The average perceived helpfulness of different treatments was calculated and expressed as mean ± SD. Furthermore, Pearson’s r or its non-parametric counterpart Spearman’s rho were applied to assess whether perceived treatment helpfulness is influenced by sociodemographic characteristics at study entry. In addition, all helpfulness variables were dichotomized (not helpful/helpful) using a cut-off ≥ 4 (moderately helpful). To assess if potential relationships exist between the patients’ perceived helpfulness and analgesic intake, pain intensities (NRS), functional ability (FFbH-R), pain-related disability (PDI) and manifestation of depressive symptoms (ADS-L) the following three steps were carried out. At first, either paired ine tool  based onine tool  and Fritine tool .A total of 276 patients completed the questionnaires at both T0 and T1. The sociodemographic characteristics of this study population are presented in Prior to treatment, mean pain intensity within the last week was rated 5.2 (5.24 ± 2.08), whereas worst and least pain was evaluated 7  and 2.8 (2.77 ± 1.93) on the NRS, respectively. On average, current pain at T0 was rated 4.4 (4.41 ± 2.42). Occasional use of analgesics was stated by 32% of the patients, whereas 14% and 23% reported analgesic intake on a regular basis and daily, respectively. Mean functional capacity (FFbH-R) at T0 was 75% (74.54 ± 16.89) which represents moderately reduced functional capacity (range 79–70). Normal functional ability was presented by 41% of the patients (range 100–80%) and nearly a quarter of the study population (23.6%) showed clinically relevant decreases in functional ability (range 59–0%). Mean pain-related disability (PDI) was 27% (26.7 ± 12.27) and clinically relevant disabilities were observed for 36% of this study population . For the ADS-L, clinically relevant depressive symptoms (ADS-L score ≥ 18) were present in 47% of the participants with 19% suffering from depression (ADS-L score > 27). The mean ADS-L score was 19.43 ± 9.53. Detailed information about pain-related characteristics are outlined in n = 208) of the patients completing the program rated the MPMP in general as helpful. Mean perceived helpfulness was 4.39 ± 1.23.As presented in n = 241, 87.3%) and individual physiotherapy as being helpful . On average, both group- and individual-based physiotherapy were perceived as very helpful . Importantly, almost half of the patients  reported that individually-delivered physiotherapy was extremely helpful to alleviate CBP. Similarly, a high percentage of patients  also rated group-based physiotherapy as extremely helpful. Following physiotherapy, most of the patients considered relaxation therapy , aquatic therapy  and back education  as beneficial. The mean perceived helpfulness of relaxation therapy (4.6 ± 1.27), aquatic therapy (4.54 ± 1.37) and back education (4.43 ± 1.3) was moderately or very helpful. In contrast, the mean helpfulness of medical training therapy (3.38 ± 1.51), biofeedback (3.31 ± 1.48), psychological pain therapy (3.15 ± 1.42) and music therapy (3.02 ± 1.47) ranged between slightly and moderately helpful. Less than two-thirds of the patients consider medical training therapy , biofeedback , psychological pain therapy  or music therapy  to be beneficial in reducing CBP.Among the different treatments, the vast majority of patients considered group-based physiotherapy  for individually-delivered physiotherapy to 3.02 (±1.47) for music therapy . In factPain location did not influence the perceived helpfulness of different treatments. Neither patients with lower or upper back pain nor participants suffering from both showed differences in their perspective on treatments helping to alleviate CBP. Similarly, smoking status was not correlated with the patients’ perceived helpfulness.s = −0.158; p = 0.009) indicating higher helpfulness ratings for patients with a lower level of chronicity. Furthermore, a weak correlation was found between chronicity status and back education treatment  suggesting that patients with higher stages of chronic pain might favor back education training.Significant but generally weak correlations with small effect sizes (Spearman’s rho) were found between several treatments and sociodemographic/pain-related characteristics . A recips = 0.147; p = 0.015) indicating that older patients tend to consider psychological interventions as more helpful. In contrast, the older the patient the less helpful device-assisted strength training  was perceived .A significant correlation was also observed between age and psychological pain therapy , psychological pain therapy  and music therapy . This suggests that the higher the education, the more likely patients were to perceive medical training therapy as helpful. The lower the education, the more likely patients were to perceive psychological and music therapies as helpful.Moreover, there were weak but significant correlations between the level of education and the perceived helpfulness of medical training therapy  and psychological pain therapies  as more helpful than did those with lower BMI scores.Patients with higher BMI scores rated aquatic  when compared to patients who worked out on a regular basis.In addition, the lack of regular sporting activity prior to the program correlates with increasing helpfulness ratings for medical training therapy. Thus, patients who did not participate in regular sports activities before study entry seem to perceive medical training therapy as being helpful to reduce CBP . Similarly, worst, least and current pain significantly improved from 6.97 ± 2.13 to 5.8 ± 2.35 , 2.77 ± 1.93 to 1.95 ± 1.85  and from 4.41 ± 2.42 to 3.07 ± 2.37 , respectively. Besides pain intensities, a 10% decrease from baseline was observed for the PDI score  and the mean ADS-L score dropped significantly from 19.43 ± 9.53 to 9.77 ± 8.27 . Treatment-induced changes in average pain intensity, pain induced disability (PDI) and depressive symptoms (ADS-L) were clinically meaningful, demonstrating the efficacy of the program. Interestingly, despite these improvements in pain-related complaints functional ability (FFbH-R) significantly decreased with a medium sized effect from 74.54% ± 16.89 to 71.49% ± 15.07  during the study. Analgesic intake was not influenced by the program.Except for the FFbH-R, large effect sizes for changes in pain-related outcome parameters were observed. Mean pain intensity decreased from 5.24 ± 2.08 at study entry to 3.80 ± 2.02  and analyzed in relation to changes in pain-related treatment outcome. Accordingly, p < 0.001, CI = −1.431 to −0.386; Δ pain worst p < 0.001, CI = −1.808 to −0.674; Δ pain least p = 0.003, CI = −0.995 to −0.095; Δ pain current p= 0.004, CI = −1.461 to −0.262). Thus, the patients’ perspective on the helpfulness of different treatments significantly corresponds to the degree of pain improvement. Furthermore, perceiving the program as helpful was associated with reduced levels of pain-related disability . Calculated effect sizes ranged from small (η2 < 0.06) to medium (Δ pain average η2 = 0.060 and Δ pain worstη2 = 0.067).Patients reporting that the MPMP in general helped to reduce back pain indeed showed significant decreases in Δ pain values during this study compared to those considering the program as not being helpful . Thus, participants experiencing individual physiotherapy as helpful did not show a greater degree of improvements in pain-related parameters when compared to patients that did not consider individual physiotherapy as being helpful to reduce CBP. Strikingly, on average, individual physiotherapy was rated as very helpful and ranked highest among the treatments.p < 0.001, CI = −2.084 to −0.744; Δ pain worst p < 0.001, CI = −2.146 to −0.666; Δ pain least p = 0.01, CI = −1.295 to −0.131; Δ pain current p = 0.006, CI = −1.854 to −0.300; Δ PDI p < 0.001, CI = −10.111 to −3.331). All measured effect sizes were small except of Δ pain average with a medium effect size of η2 = 0.069.In contrast to individually-delivered physiotherapy, patients considering group-based physiotherapy as helpful in decreasing CBP showed significantly higher degrees of improvement in pain intensities and disability than patients rating group-based physiotherapy as not helpful .After completion of the program a significantly greater degree of reduction in pain intensities with small effect sizes was observed for patients rating relaxation therapy as helpful in contrast to patients that consider relaxation therapy not helpful , when compared to the 22.1% of the study population that rated aquatic therapy as not helpful. The effect size for this association was small.Patients reporting aquatic therapy to be beneficial in reducing pain showed a higher degree of improvement in pain worst only . MANOVA revealed only small effect sizes.The degree of improvements in pain intensities was significantly greater in patients perceiving back education as helpful treatment when compared to the 25% of the study population that rated back education as not helpful . Again, effect sizes were small.For patients evaluating medical training therapy as helpful the degree of average and worst pain reduction as well as the decrease of PDI was significantly higher than for the 46.7% of the study population experiencing medical training therapy as not helpful .Significant associations with small effect sizes were found between the perceived helpfulness of biofeedback and changes in pain-related outcome parameters. Rating biofeedback as helpful was related to a higher degree of improvements in pain intensities and the PDI when compared to patients reporting that biofeedback did not help to reduce CBP .With small effect sizes, improvements of worst pain intensity were significantly greater in patients considering psychological pain therapy as being helpful to ameliorate CBP when compared to participants perceiving this treatment modality as not helpful .Importantly, patients’ perspective on the helpfulness of different treatment modalities also corresponds to changes in the FFbH-R with small effect sizes. However, MANOVA-pairwise comparisons revealed that rating treatments as helpful was significantly associated with a higher degree of impairment in pain-related functional ability. Thus, considering the following treatments as not helpful corresponds to a significantly lesser decrease in back function  considered the program as being helpful. However, focusing on specific treatment components revealed substantial differences in the perceived helpfulness. From the patients’ perspective, physiotherapy—both individually- and group-delivered—was reported to be very helpful. In contrast, psychological pain therapy and music therapy were only perceived as slightly helpful. At first this might suggest that physical treatments are perceived more effective by patients than psychological treatment approaches. However, CBP patients perceive relaxation therapy and back education  more helpful than medical training therapy. Moreover, no difference in the perceived helpfulness was observed between group-delivered physiotherapy and relaxation therapy. Previously, it was reported that patient satisfaction assessed by the treatment helpfulness questionnaire  might beTo assess whether these differences in perceived helpfulness are associated with certain patient-related characteristics, correlation analyses were performed. Several significant correlations between sociodemographic characteristics and helpfulness ratings of different treatments were identified. However, correlations were consistently weak . This indicates that individual responses to different treatment modalities are difficult to predict using sociodemographic characteristics of this study population. Similar results were reported previously . Yet, soInterestingly, back function decreased during the study, although all pain-related outcome measures improved with large effect sizes. Treatment-induced changes in average pain intensity, pain induced disability (PDI) and depressive symptoms (ADS-L) were clinically meaningful, demonstrating the efficacy of the program. In line with the treatment-induced improvements in pain characteristics, the MPMP in general was considered helpful in alleviating back pain. It remains unclear why the self-assessed functional capacity decreased. Mean functional ability was already moderately reduced at study entry. Potentially, due to the intensive program the patients reached their physical limits resulting in temporarily lower back function ratings. In fact, most adverse events of physical exercise in patients suffering from chronic pain are increased muscle pain and soreness which subside after a few weeks of the intervention as revealed by a systematic review . MoreoveLong-term results of the relation between treatment helpfulness ratings and pain-related characteristics beyond the study are not available since the patients’ perceived helpfulness was not assessed in follow-up visits. Thus, changes in the patients’ perspective on helpful treatments after completing the program need to be addressed in future studies. Analyzing the association between long-term treatment effects and perceived helpfulness could reveal clinically relevant treatment modalities impacting the patients’ pain behavior.n = 276) was available for overall analyses. Nevertheless, breaking down the integrative effect of multimodal treatments by assessing the perceived helpfulness of single treatment modalities and associations with patient-related characteristics might underestimate the overall efficacy of the MPMP. Furthermore, our results don’t include implicit treatment effects. Although perceived as activation of the body, physical treatment approaches implicitly impact pain behavior on a psychological level. Vice versa, explicitly perceived as not helpful, the implicit effect of psychological treatments is unknown and remains to be determined.Due to the amount of sociodemographic and pain-related parameters as well as the helpfulness ratings assessed in this study , approximately 70% of the study population completed all questions at both T0 and T1 and a decent number of participants (In conclusion, the patients’ perceived treatment helpfulness differs significantly between treatment modalities of multidisciplinary pain management programs and corresponds to the outcome of pain-related characteristics. However, factors determining the patients’ perspective on the helpfulness of different treatments remain unclear in this study population.


In contrast, in the DDRAM group, though leg pain score improved , there was no improvement at 6 weeks or 6 months in low back pain , physical health  or mental health . Conclusions: In our setting, the DRAM is a useful screening tool, and it has allowed the creation of a program between psychiatry and spine surgery.The Distress Risk Assessment Method (DRAM) was presented by Main, Wood and Hillis in 1992 as a simple means of assessing the risk of failure due to psychosocial factors in spine surgery. To our knowledge, it has not been used in our setting. The aim of this study was to analyse the usefulness of the Spanish translation of this instrument to predict poor outcomes. Methods: A prospective blind study was conducted including 65 patients undergoing spine surgery. We created two groups of patients based on DRAM score: not distressed (NDRAM) or distressed (DDRAM). A visual analogue scale for pain and the 12-Item Short Form Health Survey (SF-12) were used at baseline, 6 weeks and 6 months. Results: 24 patients were classified as DDRAM and 38 as NDRAM, with 3 patients not completing the questionnaires. The analysis found no significant differences in the demographic or clinical variables at baseline. At 6 weeks and 6 months, the NDRAM group showed improvements in low back pain ( Back pain is a highly prevalent condition, with estimates suggesting that at least 84% of people suffer from this type of pain at some point in their life . There iIt has long been known that patients with psychological comorbidity often have disability related to chronic back pain ,4,5. SevRecent years have seen a growing interest in measuring the perspective of patients in the evaluation of disease and the benefits of treatment. In particular, measures of health-related quality of life are becoming recognised as key tools for assessing the safety and effectiveness of surgery ,15. The p < 0.05) in leg and back pain and in disability and quality of life. In line with this, patients with higher somatization scores (MSPQ > 12) were significantly less likely to experience clinically relevant improvement (p < 0.05) in leg and back pain, as well as disability and quality of life.The Distress Risk Assessment Method (DRAM) was proposed by Main et al. in 1992  and it iThe study of Licciardone et al.  indicateThis prospective blinded study was approved by the Ethics Committee for Clinical Research of León (11 July 2016 Reference: 1668). The study population was composed of consecutive patients on the waiting list for elective spine surgery in the Spine Unit at the Hospital of León between August 2016 and February 2017. To be eligible for inclusion, patients had to be at least 18 years old. Exclusion criteria were inability to understand or complete the questionnaires by themselves. All patients were informed about the study and provided written informed consent. We have selected DRAM among the available tools because it was specifically designed for spine surgery, is self-applied and has extensive experience of use in other countries. The surgeons that indicated the procedure remained blind to DRAM scores throughout the study and no changes were done in the usual clinical intervention. Patients were assessed at baseline, 6 weeks and 6 months after surgery using a visual analogue scale (VAS) for pain and the SF-12.Two groups of patients were created based on DRAM score: Group 1: Not distressed  and Group 2: distressed  .In addition to the DRAM score, we assessed the presence of other clinical conditions including adjacent vertebral fracture, adjacent segment disease, implant rupture, pseudarthrosis and other complications .Postoperative results were considered poor if patients met any of the following criteria in the first year after surgery: further surgery as a consequence of a complication, referral for new surgery, death for any cause or a new admission for any reason in the Spine Unit, and/or hospital stay of longer than 20 days in case of fusion of three levels or more and 10 days in cases of fusion of two levels.Further, the following were recorded: any comorbidities, including anxiety or depressive disorders, asthma, autoimmune diseases, diabetes, fibromyalgia, hypercholesterolemia, hypertriglyceridemia, hypertension, kidney failure, osteoporosis, severe mental disorders and thyroid disease, and whether patients were a smoker or problem drinker. All this information was obtained from medical records. ® for Windows database was created for the study and the statistical analysis was performed with IBM SPSS Statistics for Windows, version 23 . In order to know if both groups had a normal distribution of main study variables  score, leg pain VAS score, SF-12 physical health score and SF-12 mental health score) at baseline, we performed a Kolmogorov-Smirnov test. We also performed two paired Student’s t-tests (baseline–six weeks and baseline–six months) to compare result variables in the follow-up. We also compared also categorical sociodemographic and clinical variables at baseline in order to know if exists any condition that is differently distributed between the two groups. p values < 0.05 were considered significant. An Excel2p = 0.059), asthma (chi2p = 0.205), diabetes (chi2p = 0.776), hypercholesterolemia (chi2p = 0.632), hypertriglyceridemia (chi2p = 0.815), hypertension (chi2p = 0.679), kidney failure (chi2p = 1), osteoporosis (chi2p = 1), severe mental disorders (chi2p = 0.702), spine surgery (chi2p = 0.717), or thyroid disease (chi2p = 0.059), or who were a current smoker (chi2p = 0.535), ex-smoker (chi2p = 0.958), or problem drinker (chi2p = 0.205). We did, however, detect significant differences between the two groups in the percentage of patients with a history of autoimmune diseases (chi2p = 0.025) and fibromyalgia (chi2p = 0.025), in both cases the percentage being higher in the DDRAM group.Initially, 65 patients were included in the study, but 3 did not complete the questionnaires correctly. Finally, 38 patients (58.5%) were classified into the NDRAM group and 24 (36.9%) into the DDRAM group. Baseline characteristics were similar in the two groups. Of the 65 patients, 33 were men (50.77%) and 32 were women (49.23%). They had a mean age of 55.56 years (range: 32–80 years), mean height of 1.64 meters (±0.09) and mean weight of 75.91 kilograms (±13.51). p = 0.796 and p = 0.311 respectively). On the other hand, the leg pain VAS score and SF-12 Mental Health Composite score (MCS) differed significantly between the groups (leg pain score = 7.53 (±2.09) and SF-12 MCS = 38.43 (± 10.87) in the NDRAM group vs. leg pain score = 8.54 (±1.35) and SF-12 MCS = 27.63 (±9.71) in the DDRAM group; p = 0.039 and p < 0.001, respectively).At baseline, the main study variables, namely, the low back pain VAS score and SF-12 Physical Health Composite score (PCS) (mean ± standard deviation) were similar in the two groups (low back pain score = 7.87 (±1.88) and SF-12 PCS = 24.11 (±4.91) in the NDRAM group vs low back pain score = 8.00 (±2.04) and SF-12 PCS = 25.37 (±4.28) in the DDRAM group; p = 0.108) or 6 months (p = 0.287), but in the NDRAM group, we found significant changes at both 6 weeks (p < 0.001) and 6 months (p = 0.005) (p < 0.001 and p = 0.002 for the DDRAM group and p < 0.001 and p = 0.017 for the NDRAM group)  . In the M group) .p = 0.620) or 6 months (p = 0.263), while the NDRAM group showed significant improvements at 6 weeks (p = 0.031) and 6 months (p = 0.003). Considering the SF-12 MCS (p = 0.185) or 6 months (p = 0.329), and scores had not improved significantly in the NDRAM group by 6 weeks (p = 0.137) but the improvement was significant at 6 months (p = 0.003)  .2p = 0.120). Only one patient underwent reoperation; the procedure was indicated for infection, which resolved after this treatment.The rates of clinical complications did not differ significantly between the groups  did improve, although baseline scores indicated that they had significantly greater perception of pain. In our view, back pain is a clinically more diffuse condition, which is influenced to varying extent by a wide range of factors, that is, such pain may derive from a vertebral fracture but also from muscle contracture, osteoarthritis, anxiety, etc. In contrast, radicular pain is almost exclusively attributable to stenosis causing compression of a nerve root. At baseline, the DDRAM group reported more pain and this could be related to a perceived increase in unpleasant sensations related to changes in mood.Regarding health-related quality of life, the NDRAM group showed considerable improvements, including in mental health, that could be attributed to the impact of somatic disturbance on mood and overall functioning of the patient, this being consistent with the late improvement observed. Patients must readapt themselves to improved performance, something which might not occur on a timescale of 6 weeks but be observable by 6 months. Nonetheless, the DDRAM group showed no improvement in quality-of-life parameters, with physical health or mental health, at any time point. Given this, we believe that spine surgery should not be indicated in this group of patients if the goal is to improve these parameters.The percentage of patients classified as distressed using the DRAM was notably high. In view of the results, we consider that it is essential to adopt a multidisciplinary approach to spine problems, involving collaboration between different specialists, because the presence of a somatic condition does not exclude psychiatric problems and vice versa. In order to indicate surgical procedures, we must take psychosocial factors into account because they may cause the procedure to fail . The DRAIn our study, 38% of patients in whom surgery was indicated were classified as distressed using the DRAM and did not experience significant improvements in back pain postoperatively. At baseline, leg pain scores in distressed patients were significantly higher than in non-distressed patients, but both groups reported that leg pain improved after surgery. Neither physical nor mental health improved over the follow-up in patients classified as distressed, while both improved in other patients, although improvements in mental health appeared later. In our setting, the use of the DRAM scoring has allowed the creation of a collaborative program between the psychosomatic and spinal surgery services . The DRA


Overall, 45 patients (90.0%) needed additional administration of non-opioid analgesics during postinterventional observation. Remifentanil and combined midazolam, piritramide, and S-ketamine obtained adequate analgesic effects during PTBD. After the intervention, medications with antiemetics and long-acting analgesics were more frequently administered in patients treated with remifentanil .Procedural sedation and analgesia (PSA) is important during painful dilatation and stenting in patients undergoing percutaneous trans-hepatic biliary drainage (PTBD). A prospective, nonblinded randomized clinical trial was performed comparing different analgesic regimens with regard to the patient’s comfort. Patients were randomly assigned to two treatment groups in a parallel study, receiving either remifentanil or combined midazolam, piritramide, and S-ketamine. The primary study endpoint was pain intensity before, during, and after the intervention using the numerical rating scale . The secondary study endpoint was the satisfaction of the interventional radiologist. Fifty patients underwent PTBD of whom 19 (38.0%) underwent additional stenting. During intervention, the two groups did not differ significantly. After the intervention, the need for auxiliary opioids was higher (12.5% vs 7.7%;  In patiThe synergistic effects of sedative and analgesic agents in procedural sedation and analgesia (PSA) allow low-dose administration of analgesics with fewer side effects . PSA ind22.1A prospective, non-blinded, randomized, controlled clinical trial for comparison of two different analgesic regimens was conducted from August 3, 2006, to June 20, 2008. In a parallel study, we compared conventional analgesic and sedative drugs commonly used in radiological interventions in an allocation ratio of 1:1. The study was approved by the local ethics committee (UN 2667_LEK No. 243/2.2.7) and registered (EudraCT No. 2006-003285-34).2.2All patients consecutively enrolled in the Department of Radiology, Innsbruck University Hospital, Austria, for planned PTBD and optional biliary stenting were screened for eligibility.>18 years, pre-interventional fasting >6 h, no premedication, elective procedure, American Society of Anesthesiologists (ASA) class 1–3, and written informed consent to procedure and sedation.Inclusion criteria were as follows: age Exclusion criteria were as follows: age <18 years, pre-interventional fasting <6 h, chronic analgesic treatment, emergency, ASA class 4 or 5, known allergy against PSA medication, pregnancy, or lactation period, and lack of written informed consent to procedure and sedation. Written informed consent regarding the procedure and randomized mode of sedation was obtained from all patients before intervention.2.3®; GlaxoSmithKline Pharma GmbH), midazolam , piritramide , and S-ketamine . Further medications included metamizole , diclofenac , and paracetamol .The intervention was performed in a group of four people including a specialist in anesthesiology and a specialist in radiology, both with long-standing experience in working in outsourced radiology intervention rooms. Assistance was provided by one anesthesia nursing and one radiology technician. Interventions were performed during the daytime usually lasting between 1 and 2 h. Repeated follow-up interventions were not included in this evaluation . Analges2.3.1®; Fresenius Agilia GmbH) for 5 min, dose adjustment according to organ function and anticipated pain was performed with a maximum dose of 0.25 μg/kgBW/min. Perfusion was stopped approximately 5 min before the anticipated end of the intervention.After a loading dose of remifentanil (0.1 μg/kgBW/min) administered by an infusion pump (Injectomat2.3.2Midazolam (0.02 mg/kgBW) and piritramide (0.15 mg/kgBW) were administered sequentially. S-ketamine (0.2 mg/kgBW) was administered immediately before the dilatation of the stenosis. During the postoperative observation, either piritramide, in case of strong pain, or nonopioid analgesics such as metamizole, diclofenac, or paracetamol were administered.2.3.3®, Gebro Pharma). Initial puncture of the bile duct using a 22G needle was performed under sonographic guidance and verified by an injection of contrast medium and radiological control. With a guiding wire technique, a 5F catheter was placed. After dilatation of the stenosis, the catheter was either replaced by a 6F or 7F catheter  to allow adequate drainage of bile fluid or a self-expandable metallic stent was inserted and dilated with a balloon catheter to keep the bile duct open.PTBD and biliary stenting followed a standardized protocol using a guidewire technique . Patient2.3.4Anesthesiological monitoring consisted of noninvasive blood pressure, peripheral arterial oxygen saturation, respiratory rate measurement by end-tidal capnography, and transthoracic impedance during the intervention continuously recorded with ECG in all patients. Vital signs were recorded at 5-min intervals; sedation levels were continuously monitored by anesthesiologists. Peripheral venous access was established and kept open by crystalloid infusion. Prior to intervention, all patients got either 75 mg diclofenac or, in case of gastric or renal complaints, 1 g metamizole. During the procedure, all patients received oxygen (2–5 L/min) through a face mask. For comparability, pain intensity was recorded at certain intervals, before the intervention, during local anesthesia, during dilatation, immediately after the intervention and 2 h later at the recovery room.Procedure-related complications and side effects of medications were recorded during and after the intervention. Complication assessment focused on respiratory parameters , hemodynamic parameters (blood pressure and heart rate), and frequency of postoperative nausea and vomiting (PONV) . Hypoten2.4The primary study endpoint was pain intensity before, during, and after the intervention.Pain intensity was recorded as a psychometric response using the numerical rating scale (NRS) with categories 1–3 mild pain, 4–6 moderate pain, and 7 or greater severe pain .Secondary endpoints included complications and radiologist’s satisfaction with PSA. The radiologist’s satisfaction with PSA was categorized as 1 excellent, 2 moderate, and 3 fair.2.5Power analysis revealed >80% significance with a sample size of 50 and anticipated differences in VAS score exceeding 2 ± 2 points.2.6Patients were randomly assigned to two treatment groups by random generators  18]..18].The radiologist assigned patients to interventions. The anesthetist generated the random allocation sequence and enrolled the patients the day before the operation. Neither the radiologist nor the investigating anesthetist was blinded to interventions.2.7p-value of <0.05 was deemed significant.The null-hypothesis (Ho: μ-Diff = 0) did not expect differences between the two groups, while the alternative hypothesis (H1: μ-Diff <> 0) did. The Kolmogorov–Smirnov test was used for the assessment of normal distribution. Statistical methods used to compare groups for primary and secondary outcomes included variance analysis for repeated measurements were carried out. A 3+ 15.1 years; range 27–89 years) scheduled for PTBD were enrolled in this prospective study , biliary stone disease , and benign biliary stricture . Trans-hepatic punctures were performed under sonographic and fluoroscopic guidance. The majority of patients were ASA grade III  than in patients with PSA. Overall, 45 patients (90.0%) needed additional administration of non-opioid analgesics such as metamizole, diclofenac, or paracetamol during postoperative observation (Mild pain was experienced by 25 patients (50.0%) while 17 patients (34.0%) experienced moderate pain during the intervention . Postopeervation .3.2p = 0.007) than in patients with PSA (There were no major procedure-related complications. Bradycardia was observed in ten patients (20.0%). Marked hypotension and significant respiratory depression did not occur. None of the patients experienced postoperative shivering. PONV during or immediately after the procedure was more common in the remifentanil group (33.4% vs 3.8%; with PSA . This wa3.3The radiologist reported excellent satisfaction with both anesthesia regimens – remifentanil and PSA – in 49 of 50 patients . In one 4Both regimens provided adequate analgesic effects during the intervention. Adequate postprocedure analgesia contributes substantially to patient’s comfort, and parenteral opioids remain the mainstay of pharmacologic treatment of acute pain. As maximum pain during PTBD is expected at the end of the procedure, strong analgesics with a short half-life are the preferred drugs. This favors remifentanil, a potent analgesic characterized by rapid onset and offset with a terminal half-life of 10–20 min. Context-sensitive half-life time is approximately 4 min after the infusion is stopped ,7. RemifIt is difficult to predict the likelihood of developing nausea and vomiting in patients suffering from bile duct diseases. Furthermore, bag-mask ventilation in patients with bile duct diseases may carry a certain risk of vomiting and aspiration. In our study, PONV was observed more frequently with remifentanil, when administered during general anesthesia. PONV from remifentanil when administered during general anesthesia is not frequently observed . HoweverFurthermore, in patients who are not intubated, remifentanil produces respiratory depression in a dose-dependent manner, and accidental overdose of the drug can cause severe respiratory depression and respiratory arrest . As titr2 monitoring provides noninvasive monitoring of ventilation rate and can enable early recognition of altered respiration patterns. Beyond that, assessment of accurate CO2 levels could help to detect hypercarbic patients before the presentation of hypertension, tachycardia, dysrhythmias, and acidosis.Administration of antagonists for opioids and benzodiazepine was not needed during our study. Anyway, the reversal of severe respiratory depression and muscle rigidity from opioids by the specific antidote is not ideal as this can lead to acute pain and sympathetic hyperactivity requiring intense pain control thereafter. Another disadvantage of remifentanil is depressed respiratory response to hypoxia with the insufficient stimulus to trigger breathing  – altereThe desirable characteristics of PSA medications include rapid onset of action, short duration of drug effect, rapid recovery time, reversibility with the antidote, reduction of patient anxiety, preservation of patient abilities, and few adverse effects on cardiovascular and respiratory functions. Multimodal analgesia defines the combined administration of opioids and nonopioids to take full advantage of the analgesic effects of each component while minimizing potential side effects. Combined administration of sedating, analgesic, and dissociative medications as used in this study, namely midazolam, piritramide, and S-ketamine, provided adequate analgesia. We are aware that accurate assessment of pain intensity using the NRS is less reliable in sedated patients. Furthermore, interventions might have been more painful in 19 patients who underwent additional stenting.Complications were rarely observed during our study. Marked hypotension related to myocardial depression or preexisting myocardial dysfunction or hypovolemia and blunting of the sympathetic nervous system response was not observed. Inadequate sedation and analgesia were observed in one patient in the remifentanil group during the intervention. The agitation and uncontrollable motion of the patient during the intervention are disagreeable and may even cause the failure of the procedure. Remifentanil is highly cost-effective and comparable to PSA, but when patients need overnight observation in the hospital, costs multiply very quickly.In conclusion, both regimens, remifentanil and PSA with combined midazolam, piritramide, and S-ketamine proved to be effective in providing adequate analgesic effects during PTBD. Patients treated with remifentanil more frequently needed antiemetic medication and additional long-acting analgesic medications after the intervention.


Entrapment neuropathies are a heterogenous condition reflecting distinct underlying pathomechanisms. A contemporary assessment aimed at identifying potential mechanisms may help target management for these patients. Entrapment neuropathies such as carpal tunnel syndrome, radiculopathies, or radicular pain are the most common peripheral neuropathies and also the most common cause for neuropathic pain. Despite their high prevalence, they often remain challenging to diagnose and manage in a clinical setting. Summarising the evidence from both preclinical and clinical studies, this review provides an update on the aetiology and pathophysiology of entrapment neuropathies. Potential mechanisms are put in perspective with clinical findings. The contemporary assessment is discussed and diagnostic pitfalls highlighted. The evidence for the noninvasive and surgical management of common entrapment neuropathies is summarised and future areas of research are identified. The wide variety of pathomechanisms at play in entrapment neuropathy may account for patient heterogeneity.Contemporary clinical assessment involves a detailed history, clinical examination, and additional tests if required.Noninvasive management is the first-line treatment for patients with entrapment neuropathies.Future research is required to determine whether patient stratification can improve outcomes in patients with entrapment neuropathies.135 The second most common entrapment neuropathy is cubital tunnel syndrome.100 Another common condition is “sciatica,” with reported prevalence values ranging from 1.6% to 43%.76 The striking variation in prevalence has been attributed to the varying definitions of “sciatica.”76 Indeed, “sciatica” is an arcane term which, depending on its interpretation, may include somatic referred pain, radicular pain ,19 and radiculopathy .129 Here, we use “sciatica” as an umbrella term for all 3 conditions, but use the more accurate descriptions  when studies specifically defined their patient population.Entrapment neuropathies are caused by compression and/or irritation of peripheral nerves as they travel through narrow anatomical spaces. The most common entrapment neuropathy is carpal tunnel syndrome (CTS) with a lifetime risk of 10%, which increases to a staggering 84% in patients with diabetes.134 occupational or physical factors,115 and predisposing systemic diseases such as diabetes or hypothyroidism.118 Recently, genetic predisposition is emerging as one of the strongest risk factors for entrapment neuropathies.165 In addition to rare variants,158 genome-wide association studies have identified several genetic susceptibility loci for entrapment neuropathies.165 Intriguingly, many of the genes are related to connective tissue and extracellular matrix architecture. It currently remains unclear whether these genes increase vulnerability by altering the nerve itself  or the environment through which the nerve travels .165The aetiology of entrapment neuropathies remains largely unknown. They share several risk factors across conditions, such as increased body mass index,Over the past decade, significant advances have been made in our understanding of the pathophysiology of entrapment neuropathies and their assessment and management.This article summarises the current knowledge and highlights the challenges faced when diagnosing and managing patients with entrapment neuropathies.130 and others62 have therefore refined animal models that closely mimic human entrapment neuropathies. Below, we summarise the main pathomechanisms that are associated with nerve compression in preclinical and clinical studies  and may reduce or disappear with movement.Intraneural ischaemia is typical of mild entrapment neuropathies. Animal models demonstrate that extraneural pressures as low as 20 to 30 mm Hg disrupt intraneural venous circulation.170 with subsequent oedema formation. Clinically, the presence of oedema is apparent by an enlargement of the compressed nerves169 and increases in signal intensity on specialised magnetic resonance sequences.136 Persistent oedema may eventually lead to intraneural and extraneural fibrotic changes,92 which is a feature of both radiculopathies68 and entrapment neuropathies of distal nerve trunks.28 Extraneural fibrotic changes are thought to explain the reduced gliding of human compressed nerves that is apparent during limb movements.46Prolonged ischaemia is likely to induce a compromise of the blood nerve interface130 which are often characterised by nerve conduction slowing or block.95 Ischaemia in the absence of demyelination may, however, also contribute to nerve conduction changes.73Prolonged ischaemia and mechanical compromise may induce downstream effects such as demyelination and eventually axon degeneration. Focal demyelination is a hallmark of entrapment neuropathies,131 including both downregulation and upregulation of existing ion channels as well as expression of novel channels.85 Such changes have been implicated with spontaneous ectopic generation of action potentials,26 and may contribute to spontaneous electric shock-like pain or symptoms provoked upon Tinel testing.Together with demyelination, the architecture of nodes of Ranvier changes after nerve compression,92 and that small axons are relatively resistant to compression.36 Indeed, large myelinated Aβ-fibre-mediated numbness to light touch is common as is motor neuron dysfunction apparent by myotomal muscle weakness, atrophy, and reflex changes. Guidelines on the diagnosis of entrapment neuropathies such as CTS or cervical radiculopathy thus focus heavily on large fibre tests.20 Recent evidence, however, suggests that small nerve fibre function and structure are affected in entrapment neuropathies167 and may even precede large fibre changes.141 These findings suggest that (early) diagnosis of entrapment neuropathies should include tests for small fibre function.If nerve compression/irritation perseveres, axons may eventually degenerate. It is commonly believed that entrapment neuropathies predominantly affect the large myelinated fibres 133 Intriguingly though, the neuroinflammation does not remain restricted to the lesion site, but can be found in associated dorsal root ganglia after peripheral nerve compression130 or nerve root compromise.112 Animal models of radiculopathy also demonstrate an activation of glial cells in the dorsal horn of the spinal cord.140 A similar glial cell reaction has also been reported for severe distal nerve injuries involving substantial axonal damage,67 whereas compression injuries with only minimal axonal damage seem insufficient to induce overt spinal cord neuroinflammation.130 The presence of local and remote immune inflammation has now been confirmed in patients with lumbar radicular pain using combined positron emission tomography and magnetic resonance imaging (MRI)3 The presence of remote neuroinflammation could explain the often observed spread of symptoms beyond affected dermatomes or innervation territories in patients with entrapment neuropathies172 (see https://www.youtube.com/watch?v=BZYtAR4zUpg).There is a wealth of preclinical data confirming an important role of neuroinflammation in the generation and maintenance of neuropathic pain [for review, see 130 Such epineural inflammation may sensitise the nervi nervorum21 and induce spontaneous or evoked activity in nociceptive axons resulting in mechanical hypersensitivity despite the absence of frank axonal damage.40 Arguably, such extraneural mechanisms may explain why a subgroup of patients with entrapment neuropathies has pain with a predominant nociceptive rather than neuropathic character.Of note, mild experimental nerve compression can also induce an inflammatory reaction within the epineurium.76 and inflammation10 impair retrograde and anterograde axonal transport. Its blockage can result in increased nerve mechanosensitivity,39 presumably by the accumulation and insertion of ion channels at the lesion site , and may contribute to symptoms in patients with entrapment neuropathies.Peripheral nerve compression123 central sensitisation,80 and changes to cortical representations.150 Clinical hallmarks of central mechanisms including bilateral sensory deficits in unilateral painful entrapment neuropathies,142 widespread hypersensitivity,172 and impaired conditioned pain modulation138 have been described in patients with entrapment neuropathies. Furthermore, cortical changes have been reported including functional and structural changes of the somatosensory cortex in patients with CTS150 and changes in cortical morphometry in patients with lumbar radicular pain.87 Clinically, such cortical changes may manifest in an impairment in left/right judgement tasks such as found in patients with CTS.128Because the peripheral and central nervous system form a functional entity, injuries of peripheral nerves inevitably initiate central changes. Central changes after severe experimental nerve injury include, but are not limited to, central immune-inflammatory mechanisms,12 Patients with entrapment neuropathies have continued abnormal input from the peripheral nervous system (too much or too little), which may perpetuate central adaptations. The importance of peripheral drivers in entrapment neuropathies becomes clear from clinical observations of often immediate relief of focal and widespread symptoms after decompression surgery155 or local steroid injections.97It is subject of ongoing debate, whether central changes are dependent on peripheral drivers or can drive symptoms independently.96 In patients with “sciatica,” the role of psychosocial features as prognostic factors for conservative management has either not been studied11 or remains controversial.77 Undoubtingly though, entrapment neuropathies can have strong psychosocial consequences as apparent in lumbar radicular pain affecting many aspects of life, including psychological status.124 Future work is required to conclusively determine the role of psychosocial factors in the generation, maintenance, and resolution of symptoms in patients with entrapment neuropathies.Psychosocial factors often play a role as risk factors for the development or persistence of pain. To date, the psychosocial contributions to entrapment neuropathies have not been evaluated in detail. A recent systematic review suggests that there is only limited and inconsistent evidence for a positive association of psychosocial risk factors and CTS.48 In some patients, nerve entrapment may cause pain in the innervation territory of the affected nerve55; however, extradermatomal pain distribution is common .102 Therefore, clinicians should not rule out entrapment neuropathies in the absence of clearly defined dermatomal/peripheral symptom referral patterns. Nerve entrapment may or may not cause nerve fibre damage; it may affect large and/or small fibres, and the extent of sensory fibre damage may account for heterogeneity of symptoms, ie, sensory loss and/or enhanced pain sensitivity.131 The heterogeneity of pathomechanisms likely explains the identification of subgroups of patients with radicular pain142 with differing somatosensory profiles, based on quantitative sensory testing142 and neuropathic pain screening tools.94The diagnosis and management of these patients can be challenging due to the heterogeneity of pathomechanisms and varied clinical presentation. Interestingly, nerve compression may be asymptomatic, as documented by false positive nerve root compression seen on MRI.146 Various positive sensory symptoms and signs indicating gain of function have been reported, including paraesthesia, pain attacks, and evoked pain .94 Self-reported pain profiles differ between patients with distal (CTS) vs proximal (radiculopathy) entrapment neuropathies.146 Patients with radiculopathy show an increased pain attack severity and pressure, potentially reflecting distinct underlying pain mechanisms. Another feature of gain of function seen in patients with nerve-related pain is heightened nerve mechanosensitivity, which is characterised clinically by pain to mechanical provocation of neural structures  as the presence of heightened mechanosensitivity may guide physiotherapeutic management.127The core sign of nerve damage in entrapment neuropathies is loss of function due to reduced action potential conduction caused by the nerve lesion.19 Furthermore, only 30% of patients with cervical radiculopathy are classified as having neuropathic pain based on the painDETECT questionnaire.144 However, it has to be acknowledged that neuropathic screening tools were developed before the new definition of neuropathic pain and their validity may be in question.148Although entrapment neuropathies are considered the most common cause of neuropathic pain, not all patients have obvious signs of nerve damage. For instance, radicular pain from nerve root compression can exist as a discrete disorder without a nerve root lesion and associated loss of function, ie, radiculopathy.55 The level of “probable” neuropathic pain is suggested to be sufficient to initiate pharmacological treatment for neuropathic pain.55The Neuropathic Pain Special Interest Group of the International Association of the Study of Pain introduced a grading system to assist clinicians and researchers determining the certainty of neuropathic pain Fig. .55 The l44The application of the grading system may, however, be problematic in patients with entrapment neuropathies because (1) symptoms often spread beyond the affected dermatome or innervation territories of the affected nerve, (2) patients may have very subtle sensory loss that may not be identified with bedside sensory testing and/or patients may present with mainly gain of function, and (3) diagnostic tests may not be indicated  or may be negative (see imaging and nerve conduction studies below). It therefore often remains unclear whether patients with entrapment neuropathies should receive management according to the neuropathic pain guidelines.72 Importantly, clinicians are encouraged to evaluate the presence of differential diagnoses and serious pathologies (red flags) masquerading as entrapment neuropathies , social and economic factors (blue flags) as well as occupational factors (black flags) that may contribute to the presentation.es Table .56129The physical examination includes the assessment of both musculoskeletal and related neural tissue, as well as a detailed neurological bedside examination of sensory and motor function to ascertain the presence of a nerve lesion. Results of medical investigations may assist in the diagnostic work-up. For a detailed discussion on clinical assessment of entrapment neuropathies with a focus on spinally referred pain, please consult the study by Schmid and Tampin.146 Figure 173Motor function assessment comprises the examination of reflex responses and muscle strength testing. Sensory examination must include the assessment of large and small sensory fibres because both can be affected in patients with nerve entrapment.153Several provocation tests are designed to detect nerve mechanosensitivity such as the Tinel sign or Phalen test for CTS or the Spurling test for cervical radiculopathy. However, the measurement properties of these positional tests vary greatly between studies, indicating uncertainty in their diagnostic utility.59 Although the upper-limb analogue (upper-limb neurodynamic test)47 is less known in medicine, it is extensively applied in physiotherapy practice.108 These tests comprise passive joint movements that cause movement/elongation or tension on neural structures. An abnormal response to the tests is defined as at least partial reproduction of the patient's symptoms with positive structural differentiation.108 Structural differentiation uses movements at a site remote to the painful area to further load or unload neural structures, thus differentiating symptoms of neural origin from local musculoskeletal origin.64 For detailed description of nerve mechanosensitivity testing, we refer the readers to the studies by Butler,22 Schmid and Tampin,129 and Tampin.149The straight leg raise test has been widely used to assess heightened nerve mechanosensitivity in the lower limb.30 It should be noted that in the early stages of CTS, nerve conduction studies may be unable to detect nerve injury.131 MRI is commonly used for proximal entrapment neuropathies , but often results in false negatives or positives and the affected level identified on imaging and clinical examination often does not match.159 Ultrasonography is often preferred over MRI for distal entrapment neuropathies due to its cost-effectiveness, ease of access, and possibility of quick contralateral comparison. The screening for an enlarged nerve diameter might be useful in the diagnosis of CTS121 or cubital tunnel syndrome.27 In addition to being confirmatory tests, imaging and nerve conduction tests can be important for differential diagnosis and the exclusion of serious pathologies.Additional examinations such as MRI, ultrasound, or nerve conduction studies may help in the diagnostic workup. Although nerve conduction tests are particularly useful in the diagnosis of distal entrapment neuropathies , their value for more proximal neuropathies has not been fully established.111 A similar pattern presents in patients with “sciatica,” where the clinical course is generally considered favourable; however, at least one-third will develop persistent pain and disability lasting a year or more.164 Unfortunately, prognostic factors for pain persistence remain elusive11; the most comprehensive cohort study to date in “sciatica” showed only modest associations with poor outcome for shorter pain duration, belief that symptoms will not last long and overall impact of “sciatica.”77 Unexpectedly, the strongest predictive factor  was myotomal weakness, which was, however, associated with a good prognosis. Given the failure or only weak predictive ability of traditional prognostic factors , novel approaches must be considered.Due to the scarcity of evidence in less common entrapment neuropathies, we report findings from CTS and “sciatica” only. For ethical reasons, studying the natural history of entrapment neuropathies is challenging. In CTS patients who have not received treatment over an average of 2 years, ∼23% of patients deteriorated, ∼29% remained stable, and ∼48% showed symptom recovery.174Independent of the type of entrapment neuropathy, clinical guidelines suggest a course of conservative treatment before more invasive options are considered.51 There is currently limited evidence for a short-term benefit of splinting compared to no treatment.113 Splinting is recommended at night only.51 A Cochrane review reported that there is limited evidence for a beneficial effect of exercise and mobilisation in the management of patients with CTS.114 This was supported by another review suggesting that neural mobilisation did not improve clinical outcomes compared to other treatments.16 However, more recent randomised controlled trials suggest a benefit of more comprehensive hand therapy packages.84 Given the limited literature available for the effectiveness of therapeutic management of CTS, the decision to provide physiotherapy/occupational therapy management should be based on the clinicians' expertise and patients' preferences114 while following current treatment recommendations.51For mild to moderate CTS, therapy usually includes advice, splinting, electrophysiological agents as well as manual therapy and/or exercises.106 Based on studies with mostly high risk of bias and heterogeneity of physiotherapy interventions, we found inadequate evidence to make clinical recommendations on physiotherapy for patients with “sciatica.”41 Importantly, “sciatica” definitions in available studies varied significantly and the studied populations were heterogeneous making firm conclusions difficult. There is some indication that distinct subgroups of patients may react better to certain physiotherapy treatments. For instance, patients with heightened neural mechanosensitivity seem to benefit most from neural mobilisations compared to patients with radiculopathy or radicular pain.127 Large, well-designed trials are required to determine the most effective physiotherapy approach and whether treatment stratification may improve outcome.Physiotherapy is recommended as the first-line treatment for patients with “sciatica.”110 Local steroid injections seem to have a short-term benefit only, which exceeds the effect of orally taken steroids.97 Similar results are reported by several meta-analyses for patients with “sciatica,” suggesting that nonsteroidal anti-inflammatories,119 oral corticosteroids,116 Tumour necrosis factor blockers,162 opioids,116 and specific neuropathic pain medications  do not provide better symptom relief than placebo.116 Again, corticosteroid injections seem to provide a small benefit in the short but not long term.117Oral medications do not seem to be beneficial in patients with CTS, with nonsteroidal anti-inflammatories, diuretics, or vitamin B6 not being superior to placebo.This disappointing pharmacological efficacy in patients with entrapment neuropathies may in part be due to our limited understanding of the exact pathomechanisms. Importantly, the heterogeneity of patients within one diagnosis may mask potential beneficial effects of specific subgroups. Future work is required to determine whether stratification methods could be used to identify distinct populations that may benefit from specific pharmacological interventions.45 and surgery rates are predicted to double over the coming decade,17 posing a significant challenge to public health systems. The 2 surgical approaches used are endoscopic and open carpal tunnel release, with no strong evidence indicating one technique to be more superior.160 Although CTS surgery is usually successful, ∼25% of patients do not benefit.18 Potential complications include scar tenderness, persistent symptoms, neurovascular injury, wound complication, and reduced grip strength.98 Indications for surgical consultation include moderate-to-severe or deteriorating symptoms, daily symptoms, frequent night waking, persistent symptoms causing functional impairment, not responding to nonsurgical treatments (120), and patients' preference.152Carpal tunnel decompression is the most common upper-limb surgery89 Of note, ∼4% of patients are worse after surgery137 and reoperation rates of ∼12% within 4 years have been reported after discectomy.66 Factors associated with negative postoperative outcomes include intact annulus fibrosus, longer duration of sick-leave, worker's compensation, and greater severity of baseline symptoms.168 Two systematic reviews suggest that surgery may yield faster pain relief and perceived recovery than physiotherapy or physical activity for patients with “sciatica;” however, long-term outcomes are comparable.70 Given the nonsuperiority of surgery in the long-term and the significant risks and side effects, conservative management should remain the first-line treatment. However, surgery is indicated in the presence of severe or progressive neurological deficits or persistent symptoms that are unresponsive to conservative treatment.106 Future research is needed to better understand appropriate patient selection and timelines for surgery to improve outcomes and patient satisfaction.Lumbar microdiscectomy is the most common type of surgery performed to relieve nerve root irritation or compression due to a herniated disk. Pooled data of >13,000 patients undergoing surgery for “sciatica” demonstrated that although surgery is followed by a rapid decrease in pain and disability by 3 months, patients still experienced mild-to-moderate pain and disability 5 years after surgery.154 As such, individualised management will vary in patients with entrapment neuropathy and should target the predominant dimensions. For instance, tissue-specific interventions  may be indicated in patients with clear nociceptive, heightened neural mechanosensitivity or neuropathic components. By contrast, multidisciplinary systemic treatments  may be more suitable for patients with strong cognitive–emotional, contextual, and nociplastic drivers. Future research is required to further understand specific drivers at play in individual patients, their utility for predicting outcome and treatment stratification, and the effect of personalised treatment on outcomes before a truly evidence-based management of patients with entrapment neuropathies is possible.The somewhat disappointing evidence of pharmacological, physiotherapeutic and surgical management of entrapment neuropathies clearly highlights that a one-size-fits-all approach is not successful. Considering the distinct pathomechanisms and contributing factors, contemporary management should be personalised, considering the multidimensional profile of an individual patient  Oxford Biomedical Research Centre (BRC). Brigitte Tampin was supported by the Government of Western Australia, Department of Health, and Raine Medical Research Foundation. The views expressed are those of the authors and not necessarily those of the NHS, the NIHR or the Department of Health.


Despite advances in surgical techniques and pharmacology, postoperative pain remains a common problem after appendectomy, and its management continues to be suboptimal. The aim of this study was to evaluate the effect of evening primrose oil on the reduction of postoperative pain after appendectomy.In a double-blind, randomized, clinical trial, a total of 80 adults patients with acute appendicitis who were undergoing appendectomy at the Shahid Beheshti Emdad Hospital in Sabzevar, were included. Patients were randomly allocated into two equally sized groups (n = 40). In postoperative period and after recovering from the anesthesia, each of the intervention and control groups received one evening primrose (1000 mg) or placebo capsules every 30 min for 3 times, respectively. All patients in both groups were asked to rate the intensity of their pain on a 0–10 point Visual Analogue Scale (VAS) and also McGill pain questionnaire, before and 1 h after the last administration of the drug, postoperatively.In patients who received evening primrose, both VAS and McGill pain intensity scores significantly decreased after intervention, when compared prior to initiation of the intervention (p < 0.0001). While in the control group, changes of pain intensity scores were not significantly different before and after the intervention (p > 0.05).It seems that oral evening primrose can be used as a simple and safe potential adjunctive treatment for postoperative pain control after appendectomy. Postoperative pain is one of the most frequent complaints after surgery. Most people experience pain in postoperative periods, for various reasons. It has been shown that despite advances in surgical techniques and pharmacology, up to 75% of patients in surgical wards experience moderate to severe postoperative pain –4. InappMedicinal plants have been commonplace since ancient times, and today they are commonly used in various forms, including herbal plants or their extracts throughout the world –21. EvenTo the best of our knowledge, despite the promising anti-inflammatory and analgesic effect of evening primrose oil and potential benefit of using evening primrose oil as an adjuvant for postoperative pain management, no published study evaluated its efficacy on postoperative pain.Therefore, the aim of this study was to evaluate the effect of evening primrose on postoperative pain after appendectomy.In a double-blind randomized, clinical trial, a total of 80 patients who were undergoing appendectomy and hospitalized in Emdad Shahid Beheshti Hospital in Sabzevar, Iran, were evaluated from November 2016 to May 2017. After obtaining approval from the institutional ethics committee and written informed consent from the patients, those who meet the inclusion criteria were randomly allocated into two intervention and control groups (n = 40). Inclusion criteria were Class I or II of American Society of Anesthesiologists, aged 25–75 years and weight between 40 and 120 kg. Exclusion criteria were pregnancy or lactation, previous history of surgery in the last three years; known systemic or mental psychiatric disorders such as epilepsy or schizophrenia; drugs abuser and receiving more than 2 μg/kg of fentanyl during anesthesia Also, patients treated with steroids or non-steroidal anti-inflammatory drugs were excluded from the study.After surgery, in the presence of consciousness and gag reflex (mean time of 20 min), patients in intervention group received an evening primrose capsule  every 30 min for three times, and the control group received a placebo capsule every 30 min for three times as well. One hour after last administration of the drug, patients' pain intensity were evaluated using the visual analog scale (VAS) and McGill Pain Questionnaire. All patients in both groups received Midazolam (0.02 mg/kg) for premedication, fentanyl (2 μg/kg), sodium thiopental (55 μg/kg) and 1.5 μg/kg Aesculin and 0.5 μg/kg Atracurium for induction of anesthesia. In order to maintain anesthesia, 50% Nitrous oxide, 50% oxygen and isoflurane at 1.2 MAC concentrations were given to each patient. In recovery, 1 μg/kg Fentanyl was used to relieve pain. Therefore, all patients in both groups were the same for the drugs received during and after surgery. The patients and the researcher did not know the contents of the capsules (double-blind). The evening primrose capsule contained 1000 mg and placebo capsules contained 1000 mg wheat flour. Before administration of the drugs, an anesthesia nurse who was not aware of the patients' group, evaluated patients' pain intensity and then prescribed capsules as A and B (every 30 min for 3 times) to each group. One hour after the last administration of the drug, the nurse completed the questionnaire and a checklist again. All patients in intervention group were followed for any potential adverse effects of evening primrose oil such as headache, bloating, diarrhea or abdominal pain.The data were analyzed using SPSS 20 software and Student T-test and Chi-square software.This study was registered in the Iranian Registry of Clinical Trials Database (IRCT2017092533202N3).A total of 98 patients were screened during the study period. Of these, 14 patients did not meet the inclusion criteria and 4 patients declined to participate in the study .The two groups were similar and no significant difference was observed in terms of demographic characteristics and average age. In this study, the mean age of patients was 34 ± 2 years (minimum 21 and maximum 45 years). In terms of gender, 82.5% of the subjects were male and 17.5% were female .The results of the study showed that the two groups were not statistically significantly different in terms of pain intensity prior to initiation of the intervention. In the postoperative period, the pain intensity (using both VAS and McGill questionnaires) significantly decreased in patients who received evening primrose oil when compared prior to initiation of the intervention; while in the control group the changes of pain intensity after surgery was not statistically significant .No evening primrose oil-related adverse effects were observed in the study.To the best of our knowledge, this is the first study to evaluate the effects of evening primrose oil in managing acute postoperative pain. The results of this study showed that using evening primrose oil significantly reduces postoperative pain in patients undergoing appendectomy. It has been previously confirmed that evening primrose can be used to treat many diseases with chronic inflammation . For manAccording to the results of this study, it seems that oral evening primrose oil can be used as a simple and safe potential adjunctive treatment for postoperative pain control after appendectomy. However, further well designed study with larger sample size are warranted to evaluate and determine the efficacy and optimal dose of evening primrose oil for managing acute postoperative pain.