The aim of the study was to examine the effectiveness of an intensive inpatient three-week multimodal therapy. We focused especially on the impact on the multimodal therapy outcome of the pre-admission number of treatment types patients had received and of medical specialist groups patients had consulted.155 patients with chronic low back pain and indication for multimodal therapy were evaluated with respect to pain intensity, depression, anxiety, well-being, and pre-admission health care utilization. In our controlled clinical trial we compared N = 66 patients on the waiting list with N = 89 patients who received immediate treatment. The waiting list patients likewise attended multimodal therapy after the waiting period. Longitudinal post-treatment data for both were collected at three- and twelve-month follow-ups. The impact of pre-admission health care utilization on multimodal therapy outcome (post) was analysed by structural equation model.Compared to the control group, multimodal therapy patients’ pain intensity and psychological variables were significantly reduced. Longitudinal effects with respect to pre-measures were significant at three-month follow-up for pain intensity (ES = -0.48), well-being (ES = 0.78), anxiety (ES = -0.33), and depression (ES = -0.30). Effect sizes at twelve-month follow-up were small for anxiety (ES = -0.22), and moderate for general well-being (ES = 0.61). Structural equation model revealed that a higher number of pre-admission treatment types was associated with poorer post-treatment outcomes in pain intensity, well-being, and depression.Multimodal therapy proved to be effective with regard to improvements in pain intensity, depression, anxiety, and well-being. The association between treatment effect and number of pre-admission pain treatment types suggests that patients would benefit more from attending multimodal therapy in an earlier stage of health care. Access to outpatient medical services is almost barrier-free in the German health system, that is, without any “gate-keeping-system.” This includes consultations with most medical specialists . In orthThe treatment algorithm for managing low back pain first recommends:consultation in a multimodal setting for an interdisciplinary assessment after 8–12 weeks of pain,and/or4–6 weeks out of work due to low back pain,and/orsignificant indication of a risk of chronicity , 7.In reality, patients in multimodal therapy report suffering from low back pain for many years and reveal a long history of consultations and various treatments. Most of these patients already report seriously reduced physical and emotional functioning due to low back pain , 9.Existing studies revealed several predictors of reduced pain intensity in patients with chronic low back pain following multimodal Therapy (MMT) , 11. PreThe present study aims to evaluate an intensive, three-week inpatient MMT for patients with chronic low back pain, focusing on the impact that the amount of healthcare utilization has on the outcome of MMT. The aims and hypotheses are:Evaluating the effectiveness of MMT: Compared to waiting group, patients receiving MMT were expected to improve significantly from pre- to post-treatment.Prospective evaluation at three- and twelve-month follow-ups: We hypothesized that patients would improve significantly in pain-related and psychological variables following MMT. We expected those improvements to decrease by three- and twelve-month follow-up intervals.Impact of healthcare utilization on MMT outcome: We hypothesized that the amount of pre-admission healthcare utilization would predict responses to MMT. We expected that more utilization leads to less improvement.Prior to the investigation, all participants gave written informed consent. The study was approved by the local ethics committee .0), the beginning of MMT (t1), the end of MMT (t2), and three (t3) and twelve months (t4) to follow up. Analyses for the first hypothesis were based on a pre-post-two-group design. The control group  was compared with immediately-treated patients . The outcome measures were assessed at the end of the waiting period (t1) for the waiting group and at the end of MMT (t2) for the group receiving treatment immediately. As the pre-test we used t0 (control group) resp. t1 (intervention group). The analysis for the second hypothesis was based on a one-group longitudinal design. Accordingly, all time points were considered and all patients  were included in the statistical analysis.Assessments were conducted at the beginning of the waiting time (t1 (pre-MMT-treatment) and t2 (post-MMT-treatment) of all patients (N = 155) were considered. Pre-admission healthcare utilization, pre-treatment pain intensity, depression, anxiety, and well-being served as predictors for post-treatment pain intensity, depression, anxiety, and well-being.To analyze the impact of healthcare utilization on MMT outcome (third hypothesis) the intervals tParticipants were recruited in a regular, naturalistic, German pain management setting. Criteria for participation were: (1) chronic (duration >3 months) low back pain as predominant pain condition, (2) indication for attending MMT, (3) sufficient understanding of the German language, and (4) aged between 18 and 70 years. Indication criteria for MMT were based on the German guidelines for managing non-specific low back pain. During a three-day inpatient pre-treatment multi-disciplinary pain assessment the indication was verified by an interdisciplinary team .within the study period (2008 to 2011); 182 patients proved to be eligible for MMT. Twenty-seven patients refused to sign the informed consent and were excluded. Finally, 155 patients were included in the study. Of these, sixty-six patients had a waiting period (waiting group) of at least three months prior to MMT. Patients waited for different reasons . Treatment as usual was carried out during the waiting period. Eighty-nine patients were treated immediately with MMT. N = 330 patients with chronic low back pain attended the pain center The Central Hospital in Bad Berka, Germany provides inpatient pre-treatment multi-disciplinary pain assessment (three days) and, if indicated, an intensive, three-week inpatient MMT. The main aim of the MMT was to improve functional capacity, reduce pain intensity, improve emotional functioning and well-being, and increase the patients’ knowledge of bio-psycho-social pain mechanisms and pain-related coping-strategies.An interdisciplinary therapeutic team  performed an individually-adjusted treatment within a standard schedule . Regular team meetings for the evaluation of individual treatment progress were carried out. Medical treatment consisted of modification of analgesic medication and also frequently withdrawal of medication in case of lack of effectiveness or an increasing burden of side effects. Behavioral management included education , biofeedback and cognitive-behavioral therapy  offered by psychologists. Furthermore, patients received physiotherapy  and active training sessions  offered by trained physiotherapists.All patients of the MMT group underwent pre-treatment multidisciplinary pain assessment. This included physical examination, functional testing, and further investigations to exclude red flags . Moreover psychological-, psychosomatic- or psychiatric diagnostic factors have been evaluated. The assessment team consisted of physicians , psychologists/psychotherapists, pain nurses, and physiotherapists. Based on the medical and psychological findings, an individualized treatment was recommended by the assessment team.The primary outcome was pain intensity . Secondary outcomes were depression, anxiety and well-being .German Pain Questionnaire of the German Section of the IASP (DSF: )et al. (2006) reported much lower rates for Germany. Among the European countries, Germany and Norway showed the fewest number of pain management specialist consultations, with 10% and 8% respectively. Italy and France were in the top positions with 42% and 40%, respectively, which represents chronic pain patients with at least one consultation [With regard to pre-admission healthcare utilization we found that the number of patients who had consultations with pain management specialists was 34.2% in the sample. Breivik ultation . The eleThe treatment that patients received before attending the pain center predominantly consisted of medication, physiotherapy, massage, and local injections. These are almost exclusively passive procedures, which overall are not recommended by the current guidelines for the management of low back pain . MassagAt last associations between the effectiveness of MMT and pre-admission healthcare utilization were examined. Results of the structural equation model indicate that, with an increasing number of different types of treatments received before MMT, a more negative treatment outcome has to be expected in pain intensity, general well-being, and depression after therapy. This corresponds with findings of previous researchers , 12. ThiIt could be considered whether patients with an elevated use of different treatment types might have higher scores in pain-related and psychological factors already prior to treatment. For our analyses this assumption does not hold because we statistically-controlled for baseline pain-related and psychological factors. Furthermore the generalizability is limited by the fact that we considered baseline measures only. It is still possible that these patients will have worse pain conditions in earlier stages of their treatment history. On the other hand, patients with elevated numbers of treatment types might generally have less benefit from pain treatments, including MMT. This leads to the suggestion that patients would benefit more from attending MMT in an earlier stage of healthcare utilization.Several limitations must be noted. The generalizability of the results is potentially limited. The sample consisted of consecutively-included patients from only one pain clinic.Due to the waiting setting , there was no real control group for the whole study period. Therefore no comparison with other treatments or pain conditions was possible. The waiting subgroup was a naturally formed group, and no randomization could be applied. But we found no differences with regard to pre-test values between waiting group and intervention group. Additionally, selection effects were handled by controlling pre-treatment measures in the statistical model and computation of adjusted means. A further limitation refers to the assessment of pain disability which is an important outcome measure in therapy with pain conditions . UnfortThe treatment effects of the MMT suggest that patients with chronic low back pain benefit from the intensive three-week inpatient MMT. This underlines the importance of treating low back pain with relation to physical as well as psychological aspects. The association between treatment effect and number of different pre-admission pain treatment types suggests that patients would benefit more from attending MMT in an earlier stage of healthcare utilization, thus avoiding elevated use of multiple treatment types.S1 Data(SAV)Click here for additional data file.


The present study aimed at investigating whether chronic pain patients are impaired in Theory of Mind (ToM), or Emotional Awareness.Thirty inpatients suffering from chronic somatoform pain, as well as thirty healthy controls matched for age, sex, and education were recruited. ToM abilities were measured using the Frith-Happé animation task, in which participants interpret video-clips depicting moving geometric forms that mimic social interactions. The responses given were scored for appropriateness and the degree of inferred intentionality according to established protocols. Emotional awareness was measured using the Levels of Emotional Awareness Scale (LEAS), for which participants provide written descriptions of feelings in imaginary emotional situations. Standardized scoring was performed to capture the number and quality of emotional terms used.Responses lengths were similar in both groups and for both tasks. Patients attained significantly lower intentionality but not appropriateness scores when interpreting ToM interactions. No significant group differences were found when interpreting goal directed interactions. Emotional awareness scores were significantly lower in patients compared to healthy controls.Our results suggest that chronic pain patients are impaired in mentalizing and emotional awareness. Future studies are needed to determine whether these ToM and emotional awareness deficits contribute to the etiology of somatoform pain and whether addressing these deficits in therapeutic interventions can improve polymodal pain therapy. Theory of Mind (ToM), or mentalizing, is the ability to infer on mental states, such as intentions, beliefs, or emotions in others . Two stuThe ability of patients with somatoform disorder to label and represent emotions has been investigated for several decades: A wealth of literature indicates that somatoform disorders are associated with alexithymia, the inability to identify and label emotions . HoweverThe aim of the present study was to follow up these interesting findings and to extend the existing knowledge by focusing on chronic somatoform pain, the most prevalent sub-form of somatization disorder . ChronicThe present study was approved by the ethics committee of the University of Regensburg  and conforms to the Declaration of Helsinki . WrittenThirty inpatients of the Clinic for Psychiatry and Psychotherapy at the University of Regensburg were recruited. Main inclusion criterion was the diagnosis “Pain Disorder associated with Psychological Factors” according to DSM-IV Code 307.80. An experienced physician performed the diagnosis and the evaluation of exclusion criteria, using the Structured Clinical Interview for DSM-IV (Axis I) .Thirty healthy controls were recruited successively and matched for sex, age, and education. Exclusion criteria for both groups were: major internal or neurological disorders, organic and inflammatory pain disorders, schizophrenia, major depression, current use of sedative medication, and insufficient German language skills. Exclusion criteria were evaluated in a structured interview. For the control groups the short-version of the Structured Clinical Interview for DSM-IV (Axis I) was used for screening, in order to exclude any mental disorders .The Frith-Happé-Animation task (FHAT) is a performance measure of ToM, based on animated video-clips of 34 to 45 seconds, in which two triangles exhibit the movement patterns of living beings . HealthyThe FHAT comprises four video-clips, in which two triangles display interactions suggesting „Surprising“, „Coaxing“, „Mocking“, and „Seducing”behavior—all of which require ToM for correct interpretation (ToM-condition) . As a cotype of cognitive processing which undergoes five levels of structural transformation along a cognitive-developmental sequence derived from an integration of theories of Piaget and Werner. The five levels of structural transformation are awareness of 1) bodily sensations, 2) the body in action, 3) individual feelings, 4) blends of feelings, and 5) blends of blends of feelings.” [The Levels of Emotional Awareness Scale (LEAS) is a performance test , which celings.” . Put simelings.” .Symptoms in the patient group were characterized using the German Pain Questionnaire  . The GPQAfter study inclusion, each participant was administered one of the two LEAS half-forms  at random. Each half-form comprises ten of the twenty LEAS items . ParticiResponses from both the LEAS and the FHAT were transcribed to written electronic form. The LEAS was scored according to the instructions and glossary for the German manual . FHAT-transcripts were scored on the “intentionality” and the “appropriateness” scale, according to .Two investigators scored both the LEAS and the FHAT, independently: one (A.H.) had performed data acquisition and was not blinded in respect to the study group, whereas the other (M.Z.) was blinded to grouping conditions. Analyses and conclusions were based on the blinded rater’s score.The within-subject scores for all GD and all ToM video-clips were pooled before further analysis. Mann-Whitney-U tests were used to determine potential group differences in all variables. Pearson’s correlation coefficient was used to as a measure of inter-rater reliability for both the LEAS and the FHAT. Word-counts for FHAT and LEAS responses were compared between groups and correlated with FHAT and LEAS scores to screen for potential motivational confounds.Associations between LEAS, FHAT, TAS-26, BDI-II, current pain severity, and quality of life (SF-12), were tested using the non-parametric correlation coefficient Kendall’s tau-b. Means are reported ± SD if not stated otherwise. SPSS 21.0.0.0 for Mac was used for analysis.All data are available in comma-separated format as The FHAT scores obtained by the blinded and the un-blinded investigator were strongly correlated for intentionality (r = .82) and for appropriateness scores (r = .86), denoting an acceptable inter-rater reliability. Intentionality scores were found to be significantly lower in patients, compared to controls in the ToM-, but not the GD-condition . No signThe LEAS scores obtained by the blinded and the un-blinded investigator were highly correlated (r = .93), denoting a good inter-rater reliability. Patients had a significantly lower score on all LEAS sub-scales compared to controls; effect sizes were moderate . LEAS toTAS-26 and BDI-II results indicate, that patients rated themselves as more alexithymic and depressed than controls . PatientCorrelation analyses were used to explore the relationships between LEAS, FHAT, TAS-26, BDI-II, and clinical parameters within the patient group see: . QualityThe present results show that chronic somatoform pain patients make significantly fewer references to mental states when describing social interactions involving ToM. In contrast, patients did not differ significantly from controls when describing goal directed (i.e. non-ToM) interactions  and clinical parameters  yielded mixed results. Quality of life in patients was found to be correlated with FHAT intentionality score see: , indicatNo significant associations between chronic pain-severity and any other measure were found, including quality of life. Finally, both BDI-depression and TAS-alexithymia showed a significant negative association with quality of life, which adds evidence to the notion that psychopathological rather than somatic processes may play the central role in somatoform pain.Taken together, these results indicate that ToM abilities might be relevant determinants of quality of life in somatoform pain and a worthy target for future studies. Quasi-experimental studies in which mentalizing skills are trained are necessary to determine whether these findings can be utilized clinically.The present patient sample showed several characteristics typical for somatoform pain see: . All patThe cross-sectional design and particularities of our samples are the main limitation of our present study. No causal inferences should be drawn from cross-sectional studies: The observed impairments in emotional introspection may affect the etiology and maintenance of somatoform pain, or—to the contrary—be a consequence of ongoing pain. Further, systematic group differences may explain the observed results. For example, the observed mentalizing and emotional awareness deficits may be explained by the fact that literally all patients were receiving analgesic and/or psychotropic medication at the time of testing. Accordingly, we cannot rule out that the observed introspection deficits in somatoform pain patients are side-effects of analgesic and/or psychotropic medication .Of note, we found that LEAS and FHAT scores correlated significantly with the length of participants’ responses. These correlations indicate that participants’ motivation and/or individual differences in verbal and literal expression capabilities are confounding factors for both testing instruments. Future studies with representative sample-sizes and adequate control-measures are needed to exclude that these confounds jeopardize the validity of the LEAS and the FHAT. However, the risk for confound by these factors is low for the present study, since both groups reached a similar word count on both scales.The present study provides evidence for deficits in mentalizing abilities and emotional awareness in chronic somatoform pain. Longitudinal studies are needed to determine whether these deficits play a causal or maintaining role in the etiology of the disease, or whether these deficits are epiphenomena related to ongoing pain and/or medication. Controlled trials are needed to examine whether therapeutic interventions tailored to improve patient’s introspection deficits provide additional therapeutic benefits when included in multimodal pain therapy.S1 File(CSV)Click here for additional data file.


Back pain is one of the most common health problems for which physicians are consulted, and it can considerably decrease the quality of life of patients during a great part of their lives.Our study was designed for assessing the improvement in the quality of life of patients undergoing lumbar discectomy for chronic low back pain.We included 148 patients with chronic low back pain in the analytic observational study. Using the 36-Item Short-Form Health Survey (SF-36), we evaluated the quality of life before and 6 and 12 months after lumbar discectomy.Physical and mental health scores of patients significantly improved after 6 and 12 months of lumbar discectomy. The mean improvement in physical health scores was significantly higher in female patients than in male patients. However, the improvement in mental health scores was not significantly difference between the 2 sexes and the educational and body mass index (BMI) groups.Lumbar discectomy improves both the physical and mental health subscale of the quality of life in patients with chronic disc herniation. Low back pain caused by acute disc herniation is a common disorder among patients in the age group of 20–40 years . Back paNowadays, researchers in Iran are focusing on the psychological aspects of therapeutic methods. To this end, we designed our study for assessing the improvement in quality of life of patients who underwent lumbar discectomy for chronic low back pain.This study was an analytic observational study that was performed by using the cross-sectional method. It was approved by the Baqiyatallah Medical University Ethical Board and was fully supported and funded by Baqiyatallah Medical University.Study samples included 148 patients with chronic low back pain (reported 3 months after disease onset). These patients had been referred to the neurosurgery ward of Baqiyatallah Hospital from January 2009 to May 2010. In this study, we considered variables such as age, sex, educational level, job, height, and weight. Moreover, we collected data on history of abortion, leg pain, back pain, smoking, trauma, pregnancy (including number of pregnancies), driving, sitting for long periods, and lifting heavy objects. Using this data, we evaluated the quality of life of patients before and 6 and 12 months after lumbar discectomy.We considered the quality of life after laminectomy as the outcome measure in our study. This outcome, i. e. , the patients’ HRQOL, was assessed by using the SF-36 questionnaire, which consists of 36 questions. Not only does this tool yield a total score but it also produces the 2 subscales of physical health (0–100) and mental health (0–100) A higher score suggests a better HRQOL. SF-36 has been previously validated in Iran  and has All data were entered into the computer via the Statistical Package for Social Science (SPSS) software version 14. 0 . The aim of our study was to evaluate the quality of life in patients with chronic low back pain. Paired sample t-test was used for evaluating the quality of life before and after lumbar discectomy. One sample t-test was used for comparing the improvement in mental and physical health scores  and the lowest improvement in mental and physical health scores  before and after lumbar discectomy. The mean improvement in mental and physical health scores was compared by using an independent sample t-test before and 6 and 12 months after lumbar discectomy on the basis of the patients’ sex, educational level (under diploma or higher), and body mass index (BMI) (under 25 and above that). Two-tailed significance level of 0. 05 was used to detect differences between variables.Generally, researchers have focused on the psychological aspect of therapeutic methods and have evaluated them using some variables such as the quality of life. We designed our study for assessing the improvement in quality of life of patients who underwent lumbar discectomy for chronic low back pain. 70 men (46. 6%) and 78 (53. 4%) women were included in our study. Of these patients, 56 (38. 1%) had military jobs, and 77 (53. 4%) had a diploma or higher educational level. Mean age of the patients was 44. 33 ± 11. 53 years. Mean height and weight were 165. 52 ± 11. 17 cm and 75. 21 ± 11. 47 kg, respectively. Mean BMI was 27. 62 ± 4. 39. The mean overall duration of pain between diagnosis and surgery was 34. 61 ± 54. 60 days, and mean duration of pain before diagnosis was 57. 07 ± 68. 50 days . An evaluation of the history of patients showed that 106 patients (72. 1%) had a history of lifting heavy objects, 101 (68. 7%) of sitting for long periods, 59 (40. 1%) of driving, 20 (13. 6%) of smoking, 75 (51%) of pregnancy, and 22 (15%) of abortion . The evaluation of the physical health scores of patients with chronic low back pain showed that the physical health score of patients significantly improved from 47. 46 ± 5. 13 before lumbar discectomy to 53. 43 ± 5. 11 after 6 months (P = 0. 000) and to 56. 21 ± 5. 48 after 12 months (P = 0. 000) of lumbar discectomy , 2.The evaluation of the mental health scores of patients with chronic low back pain showed that the mental health score of patients significantly improved from 38. 16 ± 5. 45 before lumbar discectomy to 42. 54 ± 4. 10 after 6 months (P = 0. 000) and to 43. 48 ± 4. 40 after 12 months (P = 0. 000) of lumbar discectomy.Comparative analysis showed that the mean improvement in the physical health score 6 months  and 12 months  after lumbar discectomy was significantly higher than the lowest improvement in physical health score. Moreover, the mean improvement in the mental health score 6 months  and 12 months  after lumbar discectomy was significantly higher than the lowest improvement in mental health score.The mean improvement in the physical health score of female patients (10. 79 ± 7. 14) was significantly higher than that in male patients ; the improvement in mental health scores of female patients (6. 29 ± 7. 40) and male patients (4. 26 ± 6. 73) showed no significant difference (P = 0. 080).The mean improvement in physical health score showed no significant difference in the 2 educational groups . The mean improvement in mental health score in the under diploma group (5. 66 ± 7. 45) and higher than diploma group (5. 01 ± 6. 87) showed no significant difference (P = 0. 590).Mean of physical health score improvement hadn’t significant difference between two BMI groups (under 25 and above that). . Moreover, the mean improvement in mental health scores of the 2 BMI groups under 25 (6. 25 ± 7. 27) and above 25 (4. 92 ± 7. 07) were not significantly different (P = 0. 310).We included 148 patients in our study. The physical and mental health scores of patients 6 and 12 months after lumbar discectomy were significantly higher than those before lumbar discectomy. Mental health improvement in men and women was not significantly different. The mean improvement in physical and mental health scores showed no significant differences between the 2 educational and BMI groups. Lumbar disc herniation is the most common disease caused by spinal degenerative processes and accounts for 30–80% of the low back pain cases . The intFor the complete assessment of benefits of a surgical intervention, it is essential to provide evidence of the influence over the patient in terms of the health status and HRQOL , 18. TheOur study had some limitations. First, we assessed the quality of life scores by using the SF-36 questionnaires; other methods may show different results. Second, the study was restricted to the Iranian population. Third, this study was conducted at a single center, and hence, the external generalizability of our findings to other countries or centers is uncertain. Lumbar discectomy improves both the physical and mental health subscale of the quality of life in patients with chronic disc herniation.


Plantar fasciitis is the most common cause of heel pain in adults. A novel alternative medical instrument, the miniscalpel-needle (MSN), which is based on an acupuncture needle, has been recently developed in China. The objective of this study was to evaluate the effectiveness of the MSN release treatment versus that of traditional steroid injection for plantar fasciitis. Patients with plantar fasciitis were randomly assigned to 2 groups and followed up for 12 months, with 29 receiving MSN treatment and 25 receiving steroid injection treatment. The results showed that visual analog scale scores for morning pain, active pain, and overall heel pain all were decreased significantly in the MSN group from 1 to 12 months after treatment. In contrast, treatment with steroid injection showed a significant effect only at the 1-month follow-up but not at 6 or 12 months after treatment. Moreover, the MSN group achieved more rapid and sustained improvements than the steroid group throughout the duration of this study. No severe side effects were observed with MSN treatment. Our data suggest that the MSN release treatment is safe and has a significant benefit for plantar fasciitis compared to steroid injection. Plantar fasciitis commonly causes heel pain and affects approximately 10% of the general population . PlantarCurrent conventional treatments for plantar fasciitis include rest, nonsteroidal anti-inflammatory drugs (NSAIDs), physical therapy, stretch exercise, and steroid injection. Steroid injection is one of the most popular options used to treat this condition , 9; howeRecently, new alternative medical instruments based on an acupuncture needle have been developed in China –17. TheyThis randomized, controlled trial was approved by the ethical committee of the First Affiliated Hospital of the Guangzhou Medical University . Patients were recruited in the outpatient clinic of the First Affiliated Hospital of the Guangzhou Medical University from July 2010 to July 2011. All patients were diagnosed based on X-ray imaging results, and 43 out of 61 patients had calcaneal spurs.n = 31) and the steroid injection group (n = 30). Two patients in the MSN group and 5 patients in the steroid injection group dropped out during the 12-month follow-up. In total, 54 patients completed the treatment protocols, and the 12-month follow-up included 29 patients in the MSN group and 25 patients in the steroid group. In the current study, all participants continued with their prior conservative treatment including physical therapy, stretching exercise, heel cushion, and NSAIDs if necessary.The allocation sequence was computer-generated with a simple randomization. The sequence was placed into sealed, consecutively numbered, and opaque envelops. Explanation of the trial was given to each patient. After informed consent was obtained, 61 patients were randomly allocated into the MSN group  was injected into the most painful tender point. After treatment, the patients in both groups were observed for 30 min to record any adverse reaction. All patients were asked to avoid bearing weight on the heel pad for 2 days and examined at 1 month after treatment. The data from the 6- and 12-month follow-up period were collected by telephone interview.The primary outcome measure was morning pain (the pain experienced during the first steps in the morning), which is a distinct feature of plantar fasciitis. Active pain (heel pain during activity) and the overall perception of heel pain were secondary outcomes. The pain was measured using the visual analog scale (VAS) between 0 and 10 points, in which 0 represented no pain and 10 represented the worst pain experienced by the patients , 20.t-test. Comparative analysis of categorical variables was performed using the Chi-square test. We used one-way ANOVA to analyze intergroup variability of the VAS scores. The analysis procedure was performed using IBM SPSS Statistics 19 software. Statistical significance was assumed if P < 0.05. Intention-to-treat analysis was performed with missing data being replaced by the last value carried forward.All values presented are mean values ± standard deviation (SD). Baseline data of the 2 groups were compared by independent-sample Plantar fasciitis patients were randomly assigned to 2 groups. In total, 54 patients completed one of the treatment protocols and the 12-month follow-up, with 29 patients in the MSN group and 25 patients in the steroid group. The baseline characteristics  are listed in P < 0.01), but there were no statistical differences in the VAS scores observed between 1, 6, and 12 months after intervention , but no significant improvement in pain was experienced at 6 or 12 months after intervention compared to the baseline levels (P > 0.05; P < 0.01; In the MSN group, the VAS scores for morning pain, active pain, and overall pain were significantly improved at 1, 6, and 12 months after intervention compared to the baseline scores (The side effects of the MSN release treatment were slight and included mild distending pain and subcutaneous bleeding at the treatment site. In total, 5 patients reported mild distending pain after intervention, and one patient experienced subcutaneous bleeding. However, the duration of all side effects was brief, and all patients recovered fully within 2 days.This is the first randomized, controlled study to evaluate and compare the effectiveness of the MSN release treatment and steroid injection for plantar fasciitis with a 12-month follow-up. The MSN group showed significantly reduced VAS scores for morning pain, active pain, and overall pain compared to the steroid injection group. Furthermore, the improvements of pain relief were maintained throughout the 12-month follow-up, suggesting that the MSN release treatment is superior to steroid injection for the long-term treatment of plantar fasciitis. In contrast, the steroid injection group showed statistically reduced VAS scores for morning pain, active pain, and overall pain only at 1 month after treatment, but not at 6 or 12 months, suggesting this treatment offers only short-term effectiveness.In most cases, plantar fasciitis is described as a self-limiting condition that will eventually resolve regardless of treatment , 4. In tIn current study, the use of prior conservative treatments was allowed. However, we recruited the patients with chronic recalcitrant plantar fasciitis failed to respond to the conservative treatments. So, these conservative treatments might not be a confounder in current study. In addition, 2 patients in the MSN group and 5 patients in the steroid infection group dropped out because of persistent heel pain in the period of follow-up.It was reported that progressive plantar fasciitis and intrinsic foot muscle stretching techniques have been shown to reduce plantar fasciitis pain. Patients can be educated on how to perform foot and ankle stretches during physician office visit , 21. RecThe significance of calcaneal spurs in patients with plantar fasciitis has been questioned in some studies –25. We fThe MSN is one new alternative medicinal instrument that has been used to treat various disorders including cervical myofascial pain syndrome and trigger thumb –15. The Steroid injection has been practiced widely, and some studies have shown good results with steroid injection for plantar fasciitis , 42, 43.Operative treatment provides a favorable effect in many studies , 44. In However, there were several limitations in this study. First, a drawback of this study is the lack of a true control group which may risk the confidence of the results. Second, the study could not keep patients blinded to the treatment type due to the nature of the interventions. Third, only subjective outcome measures were used to evaluate the effectiveness of the MSN release treatment for plantar fasciitis. Further study with a placebo controlled trial should be performed to assess the long-term effectiveness of the combination MSN with stretch exercise in the future.In this study, patients who received MSN release treatment reported more favorable and more sustained improvements in pain compared to those who received steroid injection at 1-, 6- and 12-month follow-ups. Our data suggest that the MSN release treatment offers the advantages of effectiveness, convenience, and safety for patients who have failed to respond to conventional treatments for plantar fasciitis.


This study clinically evaluated the effect of botulinum toxin type A (BTX-A) in the temporomandibular disorder (TMD) treatment using Research Diagnostic Criteria for Temporomandibular Disorders (RDC/TMD).A total of 21 TMD patients were recruited to be treated with BTX-A injections on the bilateral masseter and temporalis muscles and were followed up by an oral and maxillofacial surgeon highly experienced in the TMD treatment. For each patient, diagnostic data gathering were conducted according to the RDC/TMD. Characteristic pain intensity, disability points, chronic pain grade, depression index, and grade of nonspecific physical symptoms were evaluated. Wilcoxon signed-rank test was applied for statistical analysis.p < 0.05). Most patients experienced collective decrease in clinical manifestations of TMD including pain relief and improved masticatory functions after the treatment.The results showed that more than half of the participants (85.7 %) had parafunctional oral habits such as bruxism or clenching. In comparison between pre- and post-treatment results, graded pain score, characteristic pain intensity, disability points, chronic pain grade, and grade of nonspecific physical symptoms showed statistically significant differences after the BTX-A injection therapy (Within the limitation of our study, BTX-A injections in masticatory musculatures of TMD patients could be considered as a useful option for controlling complex TMD and helping its associated symptoms. Temporomandibular disorders (TMD), musculoskeletal disorders of the masticatory system, are common clinical labels for pain in the orofacial area. Causes of TMD symptoms are often complex and idiopathic, and problems involve extra-articular and intra-articular pathologic conditions or a combination of the both. TMD patients manifest various symptoms including myofascial tenderness and pain, headache, joint noises, trismus, and even tinnitus. In symptomatic muscle areas, a number of trigger points could be present, and palpating these musculatures generally initiates radiating discomforts along with cascading pains on multiple muscle and neuronal tracks. Depending on contributing factors, these symptoms may be transient or perpetuating .Successful TMD treatment starts from correctly differentiating the origin of symptoms. Since myofascial pains and mouth opening limitation are the most frequent symptoms in masticatory muscle disorders, directing treatments at the muscular components of TMD could yield therapeutic gains. Therefore, noninvasive conservative treatments such as counseling, soft diet, behavior medicine, physiotherapy, oral appliances, pharmacotherapy, and botulinum toxin injections are reported to be effective as first-line therapies for extra-articular pathologic conditions .Intra-articular pathologic conditions such as internal derangement and osteoarthritis could also benefit from the reversible interventions used to treat myofascial pains. Acute patients, however, may require intra-articular injection of lidocaine, hyaluronic acid, or even corticosteroid . When thThe purpose of this study was to clinically evaluate the effect of botulinum toxin injection in treating TMD arising from both intra-articular and extra-articular pathologies based on Research Diagnostic Criteria for Temporomandibular Disorders (RDC/TMD) which provides a comprehensive assessment.A total of 21 TMD patients  were recruited from Feb. 2007 to Sept. 2013 to be treated with botulinum toxin type A (BTX-A) injection. The participants had chief complaints of myofascial pain, trismus, and/or TMJ sounds. The mean age of patients was 37.0 ± 15.1 years (ranged from 15.2 to 69.0 years). A detailed sex and age distribution is shown in Table The subjects filled out the Korean-translated version of RDC/TMD Axis II questionnaires before and after the end of the treatment . The patBefore the BTX-A treatment, all patients had undergone noninvasive conservative therapies including counseling, pharmacotherapy, behavior medicine, and physical therapies. As for first-line pharmacotherapy, various medications such as NSAIDs, corticosteroids, analgesics, tricyclic antidepressants, and muscle relaxant were prescribed depending on the pathologic conditions of the patients. Physical therapies were performed in forms of low-level laser therapy (LLLT), ethyl chloride spray and stretch technique, jaw stretching exercise, and stabilization splints.This research was approved by the Institutional Review Boards of the SNUBH (IRB #: B-1305-204-110), and informed consent was obtained from all participants prior to initiating the study.BTX-A powders  were kept frozen in sterile vials until each use. Preparation of the BTX-A solution was done under the manufacturer’s guidelines. The solution was prepared by adding 0.9 % normal saline without a preservative to the powders until 2 ml of final dilution. Injection sites were wiped with 70 % ethanol swab, and dry sterile gauze for skin preparation and aspirations were performed before each injection. Calibrated 1.0-ml tuberculin syringes with 26 gauge needles were used for the injection. The prepared solution was used within an hour for its maximum potency.The patients received a total of 500 U of Dysport (BTX-A) injections into the bilateral masseter and temporalis muscles with the injection ratio of 3 to 2, respectively. Before injections, patients were asked to clench their jaws to make the injection sites more prominent. Using multiple injection technique, each masseter and temporalis muscle had three injection sites, with diffusion of approximately 1 cm apart from each sites. The treated patients were followed up by a dentist highly experienced in the TMD treatment.The characteristic pain intensity was measured by taking the mean of Q7, Q8, and Q9 and multiplied by 10. The Q7, Q8, and Q9 scores were under the GCP scale.Characteristic pain intensity (CPI)The disability points were gained by adding points for disability days and disability score. The disability days were obtained by the answer to Q10, and appropriate disability points (0 to 3) were assigned to range of days. For the disability score, the mean value of Q11, Q12, and Q13 was multiplied by 10. Appropriate disability points (0 to 3) were assigned to range of scores. All obtained scores were under the GCP scale.Disability points (DP)The chronic pain grade classification was termed as following and using previously calculated CPI and DP Table .Table 2GChronic pain grade (CPG)The mean of the numeric values (scored 0 to 4) to RDC/TMD Axis II Q20  showed the degree of psychological pain.Depression index (DI)The mean of the numeric values (scored 0 to 4) to RDC/TMD Axis II Q20 related to the pain  indicated the degree of atypical somatization and physical pain.Nonspecific physical symptoms (pain items included)The mean of the numeric values (scored 0 to 4) on RDC/TMD Axis II Q20  showed the nonspecific physical symptoms, pain items excluded.Nonspecific physical symptoms (pain items excluded)Each subject filled out the RDC/TMD Axis II questionnaire before and after the end of the treatment. Unfinished questionnaires were excluded from the study. Among the RDC/TMD, characteristic pain intensity, disability points, chronic pain grade, depression index, and grade of nonspecific physical symptoms were analyzed .Charactep < 0.05.Statistical analysis was accomplished using Wilcoxon signed-rank test  to evaluate the effectiveness of the BTX-A treatment in the subjects on pain intensity, disability days, graded chronic pain scale, depression, nonspecific physical symptoms, and jaw disability. Statistical significance was defined as n = 4), type II (n = 0), type III (n = 5), type IV (n = 8), and type V (n = 4). The patients were followed up for 2.9 ± 2.0 years by a dentist highly experienced in the TMD treatment.More than half of the participants 85.7 %) had parafunctional oral habits such as bruxism, clenching, and unilateral mastication. TMD subtypes of the patients were categorized as following according to the JSTMJ classifications (2001) [.7 % had p < 0.05). Depression index, however, did not show significant changes  and evaluation of psychological status and pain-related disability (Axis II) . With itClostridium botulinum strains, and serotype A is particularly important and the only commercially available form used in clinics for its biologic activity. The botulinum toxin serotype A (BTX-A), a naturally occurring neurotoxic protein, decreases the muscle contractions by selectively impairing the exocytosis of acetylcholine (ACH) at the neuromuscular junction of presynaptic motor nerve ending. Upon injection, this neurotoxin can effectively reduce the local muscle intensity that can last up to 3 to 6 months before forming a new muscular reinnervation and return to its full function, without significant side effects[The botulinum toxin is known to have seven serotypes (labeled A to G) produced by different e effects. BTX-A hA growing number of dentists are caring their patients with this neurotoxin for esthetic and therapeutic treatments in oral and maxillofacial areas. According to a survey, 16 % of North American dentists are estimated to use BTX-A in their practices . After iBTX-A has been used to treat a wide spectrum of medical conditions such as muscular spasm, hypertrophy, and various cosmetic corrections, and its applications are still expanding. In one report, injection of BTX-A into the lateral pterygoid muscles was recommended as the treatment choice for elderly patients with systemic/neurological diseases who experienced habitual dislocation of the TMJ . BTX-A iTraumatized TMJ could naturally self-heal or use adaptational mechanism without serious complications . When trBTX-A could also provide a control of parafunctional oral habits that involve the masticatory muscles. BTX-A is considered relatively safe since it does not cross the blood-brain barrier with its effects localized in the peripheral sensory nerves . Binder Moreover, psychosocial factors should not be ignored in diagnosing TMD since these factors sometimes influence one’s physical status –21. Myofp < 0.05). However, depression index did not show significant changes. This insists that though states of depression were not affected considerably by the injection therapy, it had positive effects on somatization (with or without pain items) and jaw disability of the TMD patients. Some studies suggest that parafunctional oral habits could be the potential risk factors for myofascial pain and disc derangement [Many studies support that BTX-A effectively diminishes the muscle activity by inhibiting triggers of excessive muscular contractions. In comparison between pre- and post-treatment results of this study, graded pain score, characteristic pain intensity, disability points, chronic pain grade, and grade of nonspecific physical symptoms showed statistically significant differences after the BTX-A injection therapy (angement . A high Even with the positive outcomes shown from the study, there are needs for more studies performed on a larger sample size, with longer follow-up periods, in order to scrutinize and evaluate the full effects of BTX-A injections. Nevertheless, within the limitation of our study, clinical injection of BTX-A in masticatory musculatures of TMD patients can be considered as a useful supportive treatment option for controlling complex TMD and helping its associated symptoms.


A promising open inguinal hernia operation called Onstep was developed in 2005. The technique is without sutures to the surrounding tissue, causing minimal tension. A specific mesh is used with a memory recoil ring in the border, which may cause pain superficial to the lateral part of the mesh for slender patients. The aim of this study was to illustrate an easy procedure that alleviates/removes the pain. A male patient had persistent pain six months after the Onstep operation and therefore had a ring removal operation. The procedure is presented as a video and a protocol. At the eleven-month follow-up, the patient was free of pain, without a recurrence. It is advised to wait some months after the initial hernia repair before removing the ring, since the mesh needs time to become well integrated into the surrounding tissue. The operation is safe and easy to perform, which is demonstrated in a video. Inguinal hernia surgery is a common procedure  and it iBecause of the promising results of the Onstep operation, it is expected that more surgeons will start to use this new technique for inguinal hernia repairs. Therefore the numbers of patients with complaints from the ring may rise and it is important that surgeons know how to remove the ring in the mesh.The aim of this study was to provide a surgical video of the procedure, which shows surgeons how to quickly and easily alleviate or remove the pain for affected patients. The video demonstrates how to remove the ring from the mesh, without increasing the risk of an inguinal hernia recurrence .2. The initial Onstep operation was performed to treat a primary inguinal hernia. After the operation, the ring in the mesh gave rise to a prominence laterally in the groin area, which caused daily pain that required an elective ring removal operation under general anesthesia. The ring removal procedure can be performed under local anesthesia as well [The patient had his primary Onstep operation six months prior to the ring removal operation, and his Body Mass Index (BMI) was 19.6 kg/m as well , but sinThe ring removal procedure is visualized and vocally explained in the video. The procedure is performed through a small incision on top of the prominence and dissection is done to the space where the mesh lies, between the internal and external oblique muscles. The lateral part of the mesh is then visualized. The next step is to identify the ring in the mesh. The ring is placed in a drawstring in the border of the mesh and is divided laterally, so that the two ends make a separate fold inside the mesh. The surgeon should cut in the mesh laterally, until one or both ends of the ring are visualized and grasp one end of the ring with a clamp. The ring can thereafter be pulled out without removing the rest of the mesh. It may be necessary to use some force to remove the ring since the mesh is well integrated in the surrounding tissue. Finally, the only steps remaining are to suture the fascia of the external oblique muscle and then the skin.http://dx.doi.org/10.1155/2016/5209095.The video is available as a supplemental file; see Video 1 in Supplementary Material available online at The prominence disappeared after removal of the ring, and the patient could return to work the same day. Preoperatively, the patient had daily pain, especially when wearing trousers. At one-month follow-up, the only pain left was when coughing heavily (the patient suffers from chronic lung disease) and the patient had no sign of a hernia recurrence. At the four- and eleven-month follow-up, the pain when coughing heavily was gone. There was still no sign of a recurrence. Overall, the patient was very satisfied with the operation.The patient in this study had a surgical removal of the ring in a permanent hernia mesh, six months after the Onstep operation. The video demonstrates the technique of how to remove the ring, with an explaining voice-over. The preoperative pain from the protruding ring was gone at the last follow-up, without development of an inguinal hernia recurrence.The Onstep operation has existed for more than 10 years and is now introduced to several European countries and very soon to the rest of the world. Advantages of this open operation are that it is easy to learn and the duration of the procedure is approximately 15 minutes. Studies have also shown that both chronic pain and recurrence rates are low, the latter ranging from 0.6%  to 3.8% Before performing the procedure of ring removal, the surrounding connecting tissue needs time to become well integrated into the mesh. This is important to ensure that the mesh stays in place when the ring is pulled out. One study showed that, after 10 weeks, tissue integration was very good for polypropylene . We normThe strength of this study was that the video illustrates the ring removal procedure well, and the technique is also explained by voice-over. The limitation of the study was that the video was obtained by the authors and not by a professional film crew. This is a case-report with the purpose of illustrating how to perform the ring removal procedure. The pioneers of the Onstep technique have removed the ring on three of the four patients with pain following Onstep, and the pain disappeared without any recurrence (one-year follow-up) . The autIn conclusion, the video demonstrates a safe and easy way to remove the ring in the mesh. Eleven months after the operation, the patient was pain-free and without a recurrence of the hernia.Video 1: Demonstration of how to surgically remove the ring in the PolySoft Mesh without removing the rest of the mesh, six months after the initial hernia repair. Also available at: .


Following Robotic-Assisted Radical Prostatectomy (RARP) patients routinely have penile pain and urethral discomfort secondary to an indwelling urethral catheter. Our objective was to assess the effect of dorsal penile nerve block with bupivacaine on urethral catheter-related pain after RARP.From 2012–2013, 140 patients with organ-confined prostate cancer were enrolled in an IRB approved double-blinded, randomized control trial comparing a dorsal penile nerve block of bupivacaine versus placebo after RARP performed by a single-surgeon. Patients were asked to complete questionnaires using the Wong-Bakers FACES Pain Rating scale while hospitalized and for 9 days post-operatively, until the catheter was removed. The primary end-points were: catheter-related discomfort, abdominal  pain, and bladder spasm-related discomfort. Secondary end-points included narcotic and other analgesic usage.120 patients were randomized to placebo vs. bupivacaine dorsal penile nerve bock. The two arms (n = 56 bupivacaine and n = 60 placebo) did not differ in preoperative, perioperative, or pathological results. There was no difference in narcotic utilization between the two cohorts. Abdominal pain was slightly lower in the bupivacaine arm at 6 hours compared to the placebo arm, but there was no difference in abdominal pain at other time points, and there were no differences in reported catheter-related discomfort or bladder spasm-associated discomfort at any of the measured time points.The data does not support the routine use of a dorsal penile nerve block with bupivacaine following RARP. Over the past decade, robot-assisted radical prostatectomy (RARP) has surpassed open radical prostatectomy as the most common surgical treatment for prostate cancer. Greater than 75% of radical prostatectomies in the United States and Europe are now performed with the da Vinci Surgical System  -approved local anesthetic of the amide group used for peripheral nerve blocks for many urologic and general surgical procedures  dorsal penile nerve block versus normal saline injection at the conclusion of RARP for localized prostate cancer.Between January 2012 and May 2013, 140 patients were initially enrolled in this study. We excluded those with chronic pain conditions, patients currently on narcotics, patients with history of indwelling-catheterization, urethral or prostatic surgery, patients allergic to bupivacaine or other local anesthetics, patients with bleeding disorders, abnormal genital anatomy or liver abnormalities. All standard FDA contraindications and warnings for bupivacaine were considered amongst our exclusion criteria. All patients signed informed consent before participating and were blinded to the randomization scheme.All patients underwent standard RARP with bilateral pelvic lymph node dissection performed by a single surgeon (KKB). The camera trocar was placed just to the left of the umbilicus and was extended at the conclusion of the procedure to allow for specimen extraction. This site was then closed with interrupted figure-of-eight sutures. All skin incisions were infiltrated with 10–20 mL of 0.25% bupivacaine. After the urethral anastomosis was complete, but prior to the placement of the final 18-French catheter, the patient received a dorsal penile nerve block using bupivacaine or an injection of saline based on their randomization assignment. The study-coordinator, who was the only team member who knew the randomization results, handed the surgeon a syringe containing either 20 mL of bupivacaine 0.25% or 20 mL of saline (placebo) for the penile block. The nerve block was performed by anesthetizing the right and left dorsal penile nerves, the deepest divisions of the pudendal nerve  pain, urethral catheter-related pain, and bladder spasm-related discomfort. The questionnaires were based on the Wong-Baker FACES Pain Rating visual analog scale (VAS), which rates pain on a 0–10 scale  and anticholinergic medication .Our standard post-operative pain regimen for patients following RARP is the following: acetaminophen 325 mg PO 1 tab every 4–6 hours for pain score 1–3 on a 10-point scale, acetaminophen/codeine 325 mg/30 mg PO 1 tab every 4–6 hours for pain score 4–6 on a 10-point scale, acetaminophen/codeine 325 mg/30 mg PO 2 tabs every 4- 6 hours for pain score 7–10 on a 10-point scale, and hydromorphone 1 mg IV every 3 hours for breakthrough pain. No patients are prescribed standing opiate medication. Patients are given standing post-operative ketorolac IV (15 mg or 30 mg) every 6–8 hours if they have normal renal function and no operative contraindication. For those who experienced bothersome bladder spasms, anticholinergic medications are given on a PRN basis in the form of oxybutynin 5 mg PO every 8 hours.On discharge, patients are prescribed acetaminophen/codeine 325 mg/30 mg PO 1–2 tab every 4–6 hours on a PRN basis. Once at home, in addition to filling out pain questionnaires, they were also asked to self-report opiate usage on a daily basis. While the above analgesic medications and dosages represent our standards following RARP, the physicians taking care of the patient were at liberty to deviate from these standards if deemed necessary.To facilitate analysis, all doses of opiates taken by the patient were converted to oral morphine sulfate equivalents doses (MED)  and bleeding disorder (n = 1). 18 patients withdrew prior to randomization, leaving 120 patients who were randomized in a 1:1 fashion to either a placebo  injection or bupivacaine dorsal penile nerve block. After randomization, no patients were lost to follow-up in the placebo group (n = 60) and four were lost in the bupivacaine group (n = 56), leaving 116 patients for final analysis  for bladder spasms, opiates usage, or ketorolac utilization or dose given. The mean ± SD inpatient opiate usage was 41.2 ± 45.5 mg for the placebo arm and 31.5 ± 24.6 mg for the bupivacaine arm  pain 6 hours after the operation in the bupivacaine arm  compared to the placebo arm (mean ± SD score of 3.7 ± 2.4) with a p = 0.004  , but subjects still reported significant discomfort  pain at the 6 hour time-point following RARP, which was statistically significantly lower in the bupivacaine arm as compared to the placebo arm. There were also no differences in inpatient or outpatient opiate analgesic utilization between the two arms.Despite the prospective, randomized, double-blinded, placebo-controlled study design, there are limitations to the study. It was calculated that 100 patients were required to detect a 25% decrease in reported pain scores. There may have been an overestimation of the effect of the nerve block, in which case, the study may be underpowered to detect statistically significant differences in pain scores. This theory is supported by the fact that the pain scores in both arms were fairly low. Although prospectively collected, the pain-ratings scales are still vulnerable to biases inherent in all questionnaires.Compared to placebo, the use of a bupivacaine dorsal penile nerve block does result in decreased self-reported abdominal  pain 6 hours following a RARP, however this decrease does not persist over time, nor are there significant differences in opiate utilization, urethral catheter-related discomfort, or bladder spasm-related discomfort. Overall, the study does not support the routine usage of bupivacaine dorsal penile block following RARP.


Chronic pain is a common and serious health problem in older patients. Treatment often includes non pharmacological approaches despite a relatively modest evidence base in this population. Hypnosis has been used in younger adults with positive results. The main objective of this study was to measure the feasibility and efficacy of hypnosis (including self hypnosis) in the management of chronic pain in older hospitalized patients.A single center randomized controlled trial using a two arm parallel group design (hypnosis versus massage). Inclusion criteria were chronic pain for more than 3 months with impact on daily life activities, intensity of > 4; adapted analgesic treatment; no cognitive impairment. Brief pain inventory was completed.Fifty-three patients were included . Depression scores improved significantly over the time only in the hypnosis group (P = 0.049). There was no effect in either group 3 months post hospitals discharge.Hypnosis represents a safe and valuable tool in chronic pain management of hospitalized older patients. In hospital interventions did not provide long term post discharge relief.ISRCTN15615614; registered 2/1/2015. Chronic pain is a common and serious health problem in the elderly. Various epidemiological studies estimate the prevalence between 25 and 65% in elderly persons who live in the community and up to 80% in institutionalized elderly people –3. The mThe management of an elderly patient with chronic pain includes both pharmacological and non-pharmacological treatment. Common drug classes are paracetamol, nonsteroidal antiinflammatory drugs (NSAIDs), and opioids . The incHypnosis is an altered state of consciousness or state of focused attention to verbal stimuli induced by the therapist (hetero-hypnosis) or the subject himself (self-hypnosis) , 9. To eThe main objective of this randomized controlled study was to measure how hypnosis can improve the management of chronic pain in older hospitalized patients. Our hypothesis was that hypnosis would be feasible and effective in decreasing pain intensity in this population. We further hypothesized that the ability to perform self hypnosis would provide a prolonged decrease in pain intensity measured 3 months after hospital discharge compared to massage.A single center randomized controlled trial using a two arm design (hypnosis versus massage) to assess the immediate and prolonged effect of hypnosis on the management of chronic pain in elderly patients. The study setting was a large geriatric hospital (300 beds).Potentially eligible patients were identified by the team in charge of the patient or by the pain and palliative care consultation team. Patients were included starting from the fifth day of hospitalization, after stabilization of their acute illnesses.Inclusion criteria were chronic pain for more than 3 months with impact on daily living activities. Intensity of pain had to be higher than 4 on a numerical pain rating scale (0–10) at inclusion despite adequate analgesia. Exclusion Criteria were: deafness; patient in his last days of life, psychosis, delirium (according to DSM-IV); cognitive impairment   post-traThe third question of the Brief Pain Inventory (BPI) (average pain) measured at inclusion (T0), week one (T1) and two (T2), at discharge (T3) and 12 weeks (T12) later was used. This item is rated on a 0 to 10 scale, where 0 = no pain and 10 = pain as bad you can imagine. The rater who completed the BPI was blinded to the allocation group .The second part  of the BPI measured at inclusion, at T0, T1, T2 and T3 . The BPIThe patient assessed his intensity of pain before and after the sessions of hypnosis and massage with a numerical rating scale rating from 0 (no pain) to 10 (pain as bad as you could imagine).Analgesic use at T0, T1, T2 and T3 was collected and doses were converted to the morphine equivalent in milligrams.To assess anxiety and mood, we used the Hospital Anxiety and Depression Scale (HADS) . It consThe functional performance of the patients was assessed by the Functional Independence Measure (FIM) completed by the team in charge of the patient at T0, T1, T2 and T3 .Baseline demographic data , as well as primary diagnosis and the co-morbidities measured by the Cumulative Illness Rating Scale-Geriatrics were collected . DetaileA randomization list to attribute patients to the two treatment groups was obtained with Stata “ralloc” function with an allocation ratio of 1, randomized block sizes ranging from 4 to 8 and no stratification.To guarantee allocation concealment the clinician called one of the authors who was not in charge of the patient and was responsible for randomized allocation.All procedures performed in studies involving human participants were in accordance with the ethical standards of the institutional and/or national research committee and with the 1964 Helsinki declaration and its later amendments or comparable ethical standards. The Ethics Commission of the University Hospital Geneva approved the study. Written informed consent was signed by each participant.The session was designed as suggested by Jensen and Petterson as a “brief hypnosis treatment” . Three sMassage is a technique that provides relaxation and improves well-being which helps reduce the feeling of pain , 28. ThrThe size of the group was determined from the results of a randomized controlled study comparing self-hypnosis and relaxation in patients with chronic pain in the setting of patients with chronic pain secondary to multiple sclerosis . A powerDescriptive statistics were reported as mean ± standard deviation for parametric data, median and inter-quartile range for non-parametric data. The hypnosis- and massage-groups were compared at baseline using t-tests or Fisher’s exact test as appropriate. Longitudinal data were analyzed according to the intention-to-treat concept (without data imputation) using linear mixed-effects regression models taking into account random effects (participant) and fixed effects (hypnosis vs massage) to predict the primary end-point with time-points, hypnosis and their interaction term as exploratory variables. These models take the repeated measure design of the study into account and allow for a different number of observations within subjects. They yield unbiased estimates of the effect size of the intervention (difference between hypnosis and massage) under the assumption that values are missing at random. Effect sizes are reported in the results section for all comparisons that showed significant between group differences over time. The level of significance was set at p < 0.05.Analyses were performed using Stata 12.1 .Over a 12-month period, 119 charts were screened  were chronic back pain , neuropathic pain , osteoarthritis  ankle ; shoulder ), fibromyalgia ; and other . Pain lasted for 6.3 ± 4.2 years. Prescribed drugs  before admission were paracetamol (acetaminophen)  opioids  , and NSAIDS , antidepressant  and antiepileptics . The only statistical significant difference regarding the characteristics of pain between both groups was the number of patients with osteoarthritis of the shoulder . On the French version of the McGill Pain Questionnaire (MPQ) descriptors of pain consist mostly in affects: two words were chosen by more than one-third of the patients: tender (36%) and ‘annoying’ (41%).Detailed results of the BPI are described in Table Prescribed drugs  at inclusion were paracetamol (acetaminophen)  opioids  , and NSAIDS , antidepressant  and antiepileptics . There were no statistically significant differences between both groups. Adjusting all models for quantity of morphine equivalent in mg did not modify the observed results. Quantity of morphine equivalent was never found significant in any regression models.Hypnosis and massage feasibility:Twenty-three patients  completed the 3 sessions of hypnosis and 17  the 3 sessions of massage. Reasons to stop the sessions were the patient died (n:3), early discharge (n:5) and patients’ refusal (n:5).Changes between sessions in the average pain measured by the BPI: Table ; Fig. 2 Changes between sessions in the pain interference score: the score decreased in both groups over time: T0 vs T1, P = 0.021; T0 vs T2, P = 0.07; T0 vs T3; P = 0.009 T0 vs T12, P:0.075). There was no difference between both groups (hypnosis compared to massage).Changes in intensity of pain before and after the session: Both groups demonstrated a statistically significant decrease in pain intensity after the sessions (P = 0.041- P = 0.034 respectively for the hypnosis and massage group).There was a significant decrease of the intensity of the pain before the session in the hypnosis group over time T1, T2, T3) compared to the massage group:  . There was no effect on anxiety.Changes in the functional status (FIM) of the patients and the quantity of morphine equivalent in mg: we could not demonstrate a significant group effect (hypnosis compared to massage), or time effect , or time*treatment interaction.Patients were discharged on average at 19.2 ± 4.4 days after inclusion. One patient died during the follow-up period. No patients had unexpected feelings, thoughts or behavior after or during the hypnotic treatment. Only three patients used auto-hypnosis after discharge (one patient 1x/week); two patients 3/week.Previous results from mixed regression models were unchanged after adjusting for pain as a reason for hospitalization, which differs between the groups after randomization."The results of this study provide interesting information about hypnosis in the management of pain in very old hospitalized patients.First, we demonstrated that hypnosis was feasible in a hospitalized older population and that chronic pain significantly decreased after the sessions. Second we confirmed our hypothesis that hypnosis had a more prolonged analgesic effect compared to massage throughout the hospital stay. Although little research addresses this issue in this population our results are supported by Ashton who found that patients who were taught self-hypnosis before coronary artery bypass surgery (mean age 64 years) needed less postoperative pain medication and had less postoperative anxiety and tension compared to a control group –18. In aThird, hypnosis had a positive effect on mood; this was not the case for massage. Possibly, hypnosis may allow patients to refocus on their abilities and resources leading to better control of their own symptoms. Post-hypnotic suggestions may also play a role. Fourth, hypnosis resulted in no adverse effects confirming its safety in older people.Contrary to our hypothesis, we found no difference in pain intensity and mood between the hypnosis and massage groups at 12 weeks post discharge. This is most likely related to the very low number of patients that continued to practice self-hypnosis three months after their discharge from hospital and suggests that further attempts at long term pain control through hypnosis and self-hypnosis should include post-discharge interventions such as reminders and efforts to maintain motivation. Audio-tapes of the sessions may also prove valuable in this regard as they encourage the practice of self-hypnosis .Recruitment was difficult and the failure to obtain differences across groups on pain interference and anxiety scores may be related to lack of power. Another limitation is the short duration of the intervention. Most studies including younger patients with chronic pain used at least 6 sessions of hypnosis –36. JensDespite the above limitations, our findings demonstrate that self-hypnosis is safe and feasible in very old hospitalized patients with multiples co-morbidities. Furthermore this technique reduced pain intensity and had a positive effect on mood. Our results indicate that hypnosis and self-hypnosis may be valuable tools in chronic pain management and suggest that health providers caring for older patients with chronic pain should be trained in this treatment modality so that it could be applied in conjunction with pharmacological treatment.Health care provider should be aware that this treatment can be provided safely and efficiently by trained physicians and nurses.


Background. Hip fracture patients represent a challenge to pain rating due to the high prevalence of cognitive impairment. Methods. Patients prospectively rated pain on the VRS. Furthermore, patients described the changes in pain after raising their leg, with one of five descriptors. Agreement between paired measures on the VRS at rest and by passive straight leg raise with a one-minute interval between ratings at rest and three-minute interval for straight leg raise was expressed by kappa coefficients. Reliability of this assessment of pain using the VRS was compared to the validity of assessing possible change in pain from the selected descriptors. Cognitive status was quantified by the short Orientation-Memory-Concentration Test. Results. 110 patients were included. Paired scores with maximum disagreement of one scale point reached 97% at rest and 95% at straight leg raise. Linear weighted kappa coefficients ranged from 0.68 (95% CI = 0.59–0.77) at leg raise to 0.75 (95% CI = 0.65–0.85) at rest. Unweighted kappa coefficients of agreement in recalled pain compared to agreement of paired VRS scores ranged from 0.57 (95% CI = 0.49–0.65) to 0.36 (95% CI = 0.31–0.41). Interpretation. The VRS is reliable for assessment of pain after hip fracture. The validity of intermittent questioning about possible change in pain intensity is poor. Since pain hinders early mobilization, various attempts have been made to improve pain treatment for this category of patients , 2. AdeqThe purpose of our study was to identify an applicable easy-to-handle instrument for formal assessment of pain and we hypothesized that (1) recitation of a five-point VRS for patients would be a reliable tool to assess postoperative pain during hospitalization after hip fracture surgery. The advantages of the VRS for formal postoperative pain assessment in this specific group of hospitalized elderly subjects are that the scale is limited to a few statements, which makes it suitable for reading aloud regardless of lighting conditions and patient's visual power and motor coordination. The VRS is also easy to use in daily clinical practice, since it requires minimal training to use the scale. We further hypothesized that (2) the commonly used practice of evaluating pain by asking the patients to compare actual pain status to previous pain, for example, after administration of analgesics, is not a reliable method in this specific group of patients when comparing to paired formally assessed descriptions of pain on a VRS.We used a prospective cohort design to assess the test-retest reliability of VRS pain measurements. The local ethics committee (Region of Southern Denmark) concluded that approval was not required for this type of questionnaire survey after evaluation of the study protocol. Patients gave their informed consent and the study was reported to the Danish Data Protection Agency .During a six-month period, patients who have had osteosynthesis of a hip fracture in three orthopaedic departments in the Region of Southern Denmark were interviewed 0 to 17 days  after surgery in hospital . Data weVariables of cognitive status were assessed using the Danish version of the inverted short Orientation-Memory-Concentration Test (sOMC) . The sOMOur scorings resulted in one set of paired measurements at rest and one set of paired measurements at straight leg raise . After cκw) [κ). The kappa coefficient represents the proportion of agreement greater than expected by chance. For intermediate kappa values between 0 and 1, Landis and Koch [Data were entered into EpiData 3.1  and double-checked for entry errors before export to Stata 10.1  for statistical analysis. To reflect the agreement between the paired measurements we used the linear weighted kappa coefficient (κw)  which aland Koch  have proTables A total of 110 patients were interviewed once between postoperative days 0 and 17  . The aveA majority of the patients were able to rate their pain using the VRS . Only thκw. When comparing agreement of the paired scores obtained from the whole population (sOMC 0–28) at rest and by straight leg raise with the previously mentioned interpretation proposed by Landis and Koch [κw-measures of 0.75 and 0.68 reach “substantial” agreement. The lowest agreement is observed by straight leg raise among the subjects stratified with most severe cognitive impairment (sOMC 0–7). The κw of 0.44 is interpretable as “moderate agreement.” Interestingly, the same group of severely impaired patients actually shows the best agreement at rest reaching a κw of 0.83 which is interpretable as “almost perfect.”Figures and Koch , the κwTables To our knowledge this is the first study to investigate retest reliability of a five-point VRS for assessment of postoperative pain during admission to hospital after hip fracture surgery. Since the obtained kappa-statistic measures of test-retest agreement of 0.68–0.75 at rest and by induced pain by straight leg raise can be interpreted as “substantial” , our priAlso the second hypothesis that evaluation of pain by simply asking the patients if pain has changed, for example, after administration of analgesics, does not consistently lead to correct answers in this specific group of patients compared to formal assessment of pain assisted by the VRS is supported since kappa-statistic measures of test-retest agreement in the whole population only reached 0.57 after one minute and 0.36 after 3 minutes.Our findings also indicate that cognitive intact and cognitive impaired patients from this population are able to report pain reliably using the VRS, which supports findings in other patient populations and in studies using other versions of the scale , 13.Several factors such as poor short-term memory, pain, medication, constant light conditions, and lack of familiar routines, which are necessary to sense time and to connect specific events, may possibly explain the inability to compare pain as experienced at different times. Nevertheless this fact emphasizes the importance of implementation of formal pain measurements tools as the VRS.In previous studies the reliability of slightly different versions of the VRS has been assessed , 14, andHip fracture is a common event in the geriatric population, and it is associated with significant pain and loss of function. Unfortunately, undertreatment of postoperative pain remains a persistent problem. Previous studies have found that hip fracture patients generally suffer from substantial postoperative pain and that age and cognitive impairment strongly influence the administered amount of analgesics in a negative direction , 14, eveWe chose the sOMC to evaluate cognitive status because this test does not require the patient to perform drawings, which requires a table surface and possible the use of glasses and sufficient light source as, for example, MMSE . In addiThe VRS is among the earliest tools for formal pain measurement, and several versions of the scale exist , 21. TheThe VRS has been criticised due to the few response categories that may not be suitable to register small changes in pain. However, even though an extension of the number of response categories could potentially increase the sensitivity of any scale, this would not necessarily make the scale more valid since small changes are not necessarily clinically meaningful or easier to interpret. However, there are statistical limitations connected to analysis of data generated from the VRS. Even though the scale categories are ranked according to severity of pain, the scale does not measure an exact relative difference between the descriptors which makes the scale ordinal. Thus, nonparametric statistics has to be used resulting in limited sophistication of statistical evaluation. Another point of criticism about the VRS is that the composition of discrete categories, of which the respondent must choose only one, induces an element of forced choice . We agreA weakness in our study is the lack of correlation to an objective “gold standard” or a corresponding scale to evaluate concurrent validity, but we actually considered the VRS to be so simple that no other scale would be directly comparable. It is also debatable if the paired answers are affected by the recall of the previous statements. We cannot exclude this influence from previous answers, but since the subjects had no detailed knowledge of the analysis of paired statements we consider that they were in fact focused on describing their actual pain rather than trying to repeat the previous statement, which could be different from their actual pain. Nevertheless we acknowledge that the possibility exists.Other papers report similarly that the VRS appears to be applicable in the elderly with a cognitive dysfunction –27 and o


The majority of patients with MFN characterized their pain by descriptors that mainly represent C-fiber-mediated pain. In QST, patients displayed elevated cold, warm, mechanical, and vibration detection thresholds and cold pain thresholds indicative of MFN. PREP amplitudes in patients correlated with cold (p < 0.05) and warm detection thresholds (p < 0.05). Burning pain and the presence of par-/dysesthesias correlated negatively with PREP amplitudes (p < 0.05). PREP amplitudes correlating with cold and warm detection thresholds, burning pain, and par-/dysesthesias support employing PREP amplitudes as an additional tool in conjunction with QST for detecting small fiber impairment in patients with MFN.To investigate the usefulness of pain-related evoked potentials (PREP) elicited by electrical stimulation for the identification of small fiber involvement in patients with mixed fiber neuropathy (MFN). Eleven MFN patients with clinical signs of large fiber impairment and neuropathic pain and ten healthy controls underwent clinical and electrophysiological evaluation. Small fiber function, electrical conductivity and morphology were examined by quantitative sensory testing (QST), PREP, and skin punch biopsy. MFN was diagnosed following clinical and electrophysiological examination (chronic inflammatory demyelinating neuropathy:  Painful polyneuropathies of different origin often affect large- and small-nerve fibers , 2 and aPainful MFN is a neuropathy encountered frequently in clinical routine, for example in patients with chronic inflammatory demyelinating neuropathy (CIDP). CIDP patients often have small fiber impairment in addition to large fiber affection . NeuropaWe therefore investigated the usefulness of PREP in assessing small fiber involvement in painful MFN. We additionally utilized QST as a standard instrument to retrieve small fiber function in neuropathy patients and compared PREP and QST data in MFN. We hypothesized that PREP amplitudes would be reduced and PREP latencies delayed particularly when elicited from the feet in patients with additional small fiber affection.In this study, eleven patients with painful MFN  were prospectively enrolled in parallel to the recruitment of healthy control subjects. The diagnosis was made when clinical signs of large fiber affection as well as neuropathic pain coincided. The recruitment of patients was performed between 2009 and 2012 at the Department of Neurology, University of Würzburg. Inclusion criteria consist of female and male patients at the age of ≥18 years, confirmed diagnosis of painful motor or sensory polyneuropathy . Exclusion criteria were: pain of other than neuropathic origin  or abnormal blood investigations not related to the neuropathy. A robust and reproducible PREP response was a prerequisite for including MFN patients in our study, as we were dedicated to delineating the differences between PREP latencies and amplitudes in patients and controls.p > 0.05 each). The performance of the study was in agreement with the Declaration of Helsinki. The study was authorized by the Würzburg Medical Faculty Ethics Committee. Recorded informed consent was received from all participants of the study.We compared our data with those from ten healthy age- and gender-matched controls recruited during our study . Inclusion criteria for control subjects comprised the following items: ≥18 years, unremarkable sural nerve conduction, no neuropathy and no report of pain (neuropathic pain or other causes of pain). The age and gender did not vary significantly between patients and control subjects  and the Neuropathy Symptoms Score (NSS) , 19. TheTo additionally identify potential depressive symptoms, we utilized the Center for Epidemiologic Studies Depression Scale  . The maxTo diagnose CIDP the Inflammatory Neuropathy Cause and Treatment (INCAT) criteria  were appz-scores, which allows normalization of the patient and control data to the data of the controls (mean and SD), i.e., also the data of the ten controls were referenced to themselves.All patients and healthy controls underwent QST. Following current recommendations –31, we lWe performed QST in each study participant on the dorsum of the foot following the standardized protocol of the German Research Network Neuropathic Pain  and using a calibrated device  , 29. We In brief: for CDT and HDT, a thermode was positioned above the dermis and the temperature lowered or raised starting at 32°C . Each control subject or patient pushed a knob when the temperature he or she sensed was cold or warm, respectively. CPT and HPT were assessed accordingly. TSL was determined by alternately changing the thermode’s temperature beginning at 32°C; the subject pushed a button to indicate when a change in temperature was felt. MDT was determined by stimulating the skin with calibrated von Frey filaments; the examination started with a von Frey filament of 16 mN and the intensity reduced or increased in the filament being sensed by the subject defining the MDT (range 0.25–512 mN). Calibrated pinpricks (range 0.25–512 mN) were applied to determine the MPT; to determine the MPS, the subject was stimulated with a pin-prick and thereafter with a brush, a Q-tip or a cotton ball; the subject then rated the degree of strength of the pinprick stimulus on a chart from 0 to 100. The VDT was determined using a tuning fork. A calibrated algesiometer  was used to assess the PPT.z-score utilizing the formula: z-score [/SD of control subjects]. Calculating the z-score allows the normalization of patient data to the control group. Positive z-scores reveal a gain of function whereas negative z-scores point to a loss of function in comparison to the controls. Since in this formula the controls’ QST values are normalized to their own mean and SD, the controls’ QST z-score values result in zero with a SD of one. Since the MPS examination may result in “zero,” we applied the Bartlett procedure  for reproducible N1- , P1-  latencies, and peak-to-peak amplitudes (PPA). Every curve was analyzed off-line via an examiner blinded to the diagnosis on coded data files. Recordings containing technical or biological artifacts were excluded from the analysis. Only those recordings were included that showed robust and reproducible potentials. Additional exclusion criteria for PREP recordings were: history of epilepsy, cardiac pacemakers, and deep brain stimulators.All patients and healthy controls underwent PREP derived from Cz via a needle electrode sited subcutaneously and referenced to connected ear lobes  as formerly mentioned in detail . Signal All patients underwent skin punch biopsies with a size of 5 mm  obtained to assess intra-epidermal nerve fiber density (IENFD). The locus for the removal of the biopsies was the lower extremity 10 cm proximal to the lateral malleolus. The skin probes were treated as specified formerly . ImmunorU test, and the parametric student’s t-test to compare data with normal distribution. Data without normal distribution are shown as median and range , whereas data that show a normal distribution are illustrated as mean ± SD (PREP as well as QST data). For comparison with previously published data, the McGill pain questionnaire results are depicted as mean ± SD. For correlation analysis, the Pearson Product Moment correlation was utilized. The level of significance was set to p < 0.05.We used Statistica 64 10  for statistical analysis and Sigma Plot 11.0 for Windows  for graph creation. Normally distributed data was subjected to the Shapiro–Wilk test. To compare data without normal distribution, we applied the non-parametric Mann–Whitney n = 5, gabapentin n = 2), whereas the controls received no analgesic therapy.Our study cohort’s demographics, neuropathy scale scores, questionnaire results, and electrophysiology data are summarized in Table p < 0.05, Figure p < 0.05, Figure p < 0.05 vs. controls, Figure The detection thresholds of MFN patients as well as control subjects are illustrated in Table S2 in Supplementary Material. MFN patients had more elevated CDT and WDT than the control subjects (n = 6) compared to controls revealed no intergroup difference. Between PREP PPA induced at the feet and thermal perception thresholds  of MFN patients a positive correlation was encountered , whereas less than half of the patients experienced pressure, evoked, or paroxysmal pain . In contrast, our healthy control subjects reported no burning, pressure, evoked or paroxysmal pain. In the McGill pain questionnaire, MFN patients characterized their pain using sensory and affective pain descriptors, whereas the controls reported no pain . To define the predominance of Aδ- or C-fiber-mediated pain, the total amount of the “dull” or “pressing” pain descriptor selections was calculated from the McGill pain questionnaire data . This suOur results demonstrate that, in addition to QST, PREP amplitudes may provide a useful parameter reflecting functional small fiber impairment in patients with painful MFN. This observation is underpinned by the strong correlation among increased thermal perception thresholds and reduced PREP amplitudes in patients with MFN, and by the correlation between ongoing burning pain as well as par- and dysesthesias and reduced PREP amplitudes.Similar results have been obtained using other methods in small fiber neurophysiology. Nociceptive N2/P2 latencies were delayed and CHEP and LEP amplitudes reduced or even absent in MFN compared to healthy controls . The N2/Our MFN cohort consisted of different diagnostic subgroups . It is known that the type of neuropathy can affect cerebral pain-associated potentials; e.g., LEP may be absent in metabolic or toxic neuropathies . Thus, fMoreover, due to the small sample size of cohorts, demographic factors such as gender and age cannot be investigated by this study. It is of great interest to determine the influence of these factors on PREP parameters in a future large-scale study.Due to the short anode-to-cathode distance design of the concentric electrode nociceptive afferents in the superficial skin are activated. By this electrode arrangement, a high current intensity is gained when choosing low current stimulation. Furthermore, the electrical stimulation caused a pin-prick sensation that is a phenomenon associated with the excitation of Aδ -fiber nociceptors –44, and Therefore, this factor probably does not account for the lack of a difference between our patients’ and controls’ PREP parameters. The characterization of late components of PREP needs future studies. This may help to differentiate between the excitation of different fiber types similar to the reported early and late components of LEP indicating Aδ- or C-fiber excitation .in vitro evidence suggests, nociceptive transmission in the dorsal horn is altered by anticonvulsant drugs such as gabapentin and pregabalin (Another issue is the potential influence of analgesic drugs on PREP parameters. As experimental egabalin , 53; humegabalin . Thus, wegabalin , 29. Theegabalin , 56, PREThe absent correlation between skin biopsy results and PREP parameters is in agreement with antecedent reports , 13. ThiOne reason why burning pain revealed no correlation with the IENFD in MFN patients might be that preserved C-nociceptors may cause spontaneous ectopic discharges resulting in pain –59. In aDifferent pain phenomena might indicate potential pain mechanisms in MFN patients , 61. ThiIn summary, our data suggest that PREP amplitudes may be a sensitive and non-invasive marker of small fiber impairment in painful MFN in conjunction with QST. However, it is crucial to endorse that the clinical diagnosis of small fiber impairment in MFN can only be made by performing other small fiber tests in addition to recording PREP. Our findings support PREP amplitudes as an adequate tool to measure small fiber conductivity in patients with MFN or for follow-up after pharmacotherapy. Large-scale future investigations are required to demonstrate the utility of PREP in different subgroups of MFN patients as an instrument for better differential diagnosis and treatment.NH, NÜ, CS wrote the manuscript, designed the study, and undertook statistical analysis; NH and AK performed the experiments; CS, DZ, NÜ, NH analyzed data; ZK revised the manuscript for relevant intellectual content.The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.