Endoscopic submucosal dissection (ESD) is an advanced therapy for early gastric neoplasm and requires sedation with adequate analgesia. Lidocaine is a short-acting local anesthetic, and intravenous lidocaine has been shown to have analgesic efficacy in surgical settings. The aim of this study was to assess the effects of intravenous lidocaine on analgesic and sedative requirements for ESD and pain after ESD.Sixty-six patients scheduled for ESD randomly received either intravenous lidocaine as a bolus of 1.5 mg/kg before sedation, followed by continuous infusion at a rate of 2 mg/kg/h during sedation  or the same bolus and infusion volumes of normal saline . Sedation was achieved with propofol and fentanyl. The primary outcome was fentanyl requirement during ESD. We recorded hemodynamics and any events during ESD and evaluated post-ESD epigastric and throat pain.P < 0.001). The lidocaine group reached sedation faster , and incidence of patient movement during ESD decreased in the lidocaine group . Numerical rating scale for epigastric pain was significantly lower at 6 hours after ESD  and incidence of throat pain was significantly lower in the lidocaine group . No adverse events associated with lidocaine were discovered.Fentanyl requirement during ESD reduced by 24% in the lidocaine group compared with the control group (105 ± 28 vs. 138 ± 37 μg, mean ± SD; Administration of intravenous lidocaine reduced fentanyl requirement and decreased patient movement during ESD. Moreover, it alleviated epigastric and throat pain after ESD. Thus, we conclude that the use of intravenous adjuvant lidocaine is a new and safe sedative method during ESD. As ESD outcomes and complications can be determined by sedation method,3 it is important to provide better sedation during ESD. Furthermore, efforts to reduce post-ESD pain are needed because moderate to severe epigastric pain is common after ESD.4 Several studies have reported methods for reducing pain from ESD, including transdermal fentanyl patch, submucosal injection of local lidocaine or bupivacaine, intravenous (IV) dexamethasone, and IV magnesium.9Endoscopic submucosal dissection (ESD) is the current standard therapy for premalignant lesions and early stomach cancers because this procedure markedly improves en bloc resection, histologically complete resection, and localized tumor recurrence rates compared with endoscopic mucosal dissection.12 IV lidocaine was originally intended to be an antiarrhythmic drug but has been used in various surgical settings.12 Perioperative use of IV lidocaine, especially for abdominal surgery, has been shown to reduce anesthetic or analgesic requirements, postoperative pain, postoperative nausea and vomiting, and has resulted in earlier return of bowel function and shorter hospital stay.14 We previously reported that use of IV magnesium, which showed analgesic efficacy in surgical settings, also reduced the analgesic requirement during ESD and decreased epigastric pain after ESD.9 In accordance, IV lidocaine might be another effective analgesic for ESD.Lidocaine, developed in 1948, is an amide-type short-acting local anesthetic and has analgesic, antihyperalgesic, and anti-inflammatory properties.This randomized study assessed the effects of IV lidocaine administered as a bolus injection (1.5 mg/kg) followed by a continuous infusion (2 mg/kg/h) on sedative and analgesic requirements during ESD and on post-ESD pain.http://clinicaltrials.gov (registration number: NCT02543411). Between September 2015 and November 2015, 66 patients aged between 20 and 80 years who were scheduled for ESD to treat early gastric neoplasm  were included. ESD was scheduled on the basis of standard criteria: histological diagnosis of a well or moderately differentiated adenocarcinoma or dysplasia (adenoma); tumor invasion of the mucosa or minute submucosal layers defined by endoscopic ultrasonography; tumor size ≤3 cm if minute submucosal invasion or tumor with ulceration was suspected; and tumor of any size if it was a differentiated adenocarcinoma without ulceration or submucosal invasion. Written informed consent was obtained from all patients before randomization. Patients were excluded if they met at least one of the following criteria: hypersensitivity to lidocaine, chronic pain, chronic abuse of opioid or nonsteroidal anti-inflammatory drug, atrioventricular block, liver or renal dysfunction, multiple gastric lesions, or gastrointestinal pain.This study was approved by the institutional review board and Hospital Research Ethics Committee of Severance Hospital in the Yonsei University Health System (protocol number: 4-2014-0933) and was registered at http://www.random.org). Study medications were prepared in bags and syringes of identical appearance by a staff nurse who was not involved in the study. Lidocaine was prepared as follows: 1.5 mg/kg of 1% lidocaine diluted with normal saline to a total volume of 100 mL for the bolus dose and 20 mL of 1% lidocaine mixed with 20 mL of normal saline for a concentration of 5 mg/mL for continuous infusion. Patients in the lidocaine group (n = 33) received IV lidocaine as a bolus dose of 1.5 mg/kg before sedation, followed by a continuous infusion at a rate of 2 mg/kg/h during sedation. Patients in the control group (n = 33) received an equal volume of normal saline as a placebo following the same protocol used for lidocaine bolus and infusion. The bolus was administered over 10 minutes before sedation induction at the pre-anesthetic care unit, and continuous infusion was started simultaneously with sedation induction and continued throughout the procedure. The anesthetic administrator, endoscopists, nurses, patients, outcome assessors, and data analysts were all blinded to patient assignment until analysis completion.Patients were randomly assigned into either the lidocaine group or the control group in a 1 : 1 ratio by computer-generated randomization (2), noninvasive blood pressure (NIBP), capnography, and electrocardiography (ECG) with respiratory activity via thoracic leads were monitored. Supplemental oxygen was provided via the nasal cannula at a rate of 3 L/min. After loading 5 to 7 mL/kg of normal saline or Ringer's lactate solution, fluid infusion was maintained at a rate of 3 to 5 mL/kg/h. Before the procedure, all patients were informed to indicate any discomfort or pain during procedure by raising his or her right hand.All patients were sedated using Monitored Anesthesia Care performed by an experienced anesthesiologist. During the procedure, pulse oxygen saturation  or mean blood pressure (MBP) increased by >20% of baseline or if the patient raised his or her hand to indicate pain according to the prior instructions, a 0.5 μg/k g bolus of fentanyl was administered. If an increase of MBP persisted despite propofol or fentanyl administration, 10 mg of IV labetalol was administered. In cases of MBP <60 mm Hg or HR <40 beats/min, IV ephedrine 4 mg or atropine 0.5 mg was administered, respectively. In apnea or desaturation with SpO2 <90%, supplemental oxygen was increased to 5 L/min, and airway modification, including chin lift, jaw thrust, or assisted mask ventilation, was applied on the basis of the clinical judgment of the attending anesthesiologist. If desaturation persisted despite such interventions, the propofol infusion was decreased or stopped.All patients received butylscopolamine  as premedication. The patients were initially sedated with an IV bolus of 0.5 mg/kg of propofol  and 1 μg/kg of fentanyl . Sedation was maintained with continuous propofol infusion at a rate of 60 μg/kg/min, along with an intermittent fentanyl bolus of 0.5 μg/kg. Propofol infusion was terminated upon coagulation, which began after specimen dissection. The targeted depth of sedation was 3 or 4 of the Modified Observer Assessment of Alertness/Sedation (MOAA/S) scale. MOAA/S scores range from 0 to 6 .2, NIBP, and ECG. Patients were assessed by nursing staff using Aldrete scores and discharged when they reached a total Aldrete score of 8, including a respiratory score of 2.15ESD procedures were performed by experienced endoscopists who were blinded to patient assignment, and a single-channel upper gastrointestinal endoscope  was used. The procedure was performed in the following sequence: the resection margin was marked, the mucosa was elevated, the submucosa was incised/dissected, and the resection bed was coagulated. After identification of the target lesion, several dots were made circumferentially 5 mm outside of the tumor, using argon plasma coagulation. Then, submucosal injection of a saline solution and an epinephrine mixture  was performed to elevate the lesion off of the muscular layer. A circumferential incision was made in the mucosa with a needle knife in order to separate the lesion from the surrounding non-neoplastic mucosa. Next, the submucosal layer was dissected directly using an insulated-tip knife, until complete removal was achieved. If necessary, submucosal injections were repeated during the procedure, and endoscopic hemostasis and ablation of visible vessels were achieved using a hemoclip or hemostatic forceps. After the procedure, patients were transferred to a recovery room and monitored with regard to SpOTotal administered doses of fentanyl and propofol during ESD were recorded. HR and MBP were collected at 7 separate time points: before sedation induction (T0); after sedation induction (T1); submucosal injection of epinephrine (T2); 5, 10, and 20 minutes after submucosal dissection ; end of the procedure (T6). The degree of bleeding  and the presence of fibrosis was checked during the procedure. The definition of “en bloc resection” was tumor resection in a single piece without fragmentation and “complete resection” was complete tumor resection with a histologically tumor-negative resection margin. “Procedure time” meant the time from endoscopic insertion to the endoscopic removal and “time to sedation” meant the time from propofol bolus injection to moderate-to-deep sedation (MOAA/S score ≤3). Gagging during endoscopic insertion and involuntary movement during the procedure, such as raising of the head, moving of hands toward the endoscopy site, attempting to sit in the upright position, and retching, were recorded.Upon arrival in the recovery room, MOAA/S scale was assessed for each patient. Epigastric and throat pain were checked in the recovery room or in the ward at 30 minutes, 6, and 24 hours after the procedure. The pain intensity was checked with an 11-point numerical rating scale . When patients reported an NRS score >5 or patients requested additional analgesics, 0.5 μg/kg of IV fentanyl was administered in the recovery room, and 30 mg of IV ketorolac or 50 mg of IV tramadol was administered in the ward. Nausea or vomiting was recorded up to 24 hours after the procedure. The length of recovery room stay and hospital stay were recorded. Adverse events related to the procedure such as leukocytosis , fever (>38°C), bleeding (required blood transfusion or >2 g/dL decrease in hemoglobin level after ESD), perforation , atelectasis, or pneumonia , as well as events related to lidocaine administration such as arrhythmias or signs of lidocaine toxicity, were assessed throughout the hospital stay.9 When a 25% reduction of fentanyl consumption is considered to be clinically relevant,16 an enrollment of 28 subjects per each group was required at a significance level of 5% and a power level of 80%. For possible dropouts, 33 patients per each group were included.The primary endpoint of this study was total administered dose of fentanyl during ESD. In a previous study, the mean ± standard deviation (SD) of administered fentanyl dose during ESD was 126 ± 41 μg.t test and the Mann–Whitney U test were used for parametric and nonparametric data, respectively. The Chi-square test or Fisher exact test was used for categorical variables as appropriate. Repeated-measured data within the group, such as HR and MBP, were analyzed with a linear mixed model. When the interaction was statistically significant, posthoc test was performed and the P value was adjusted with Bonferroni correction. A P value of <0.05 was considered statistically significant. Statistical analysis was performed using PASW Statistics 20  and SAS 9.2 .Data are expressed as mean ± SD, median (range), or number of patients (proportion). Normality of distribution was assessed with a Q–Q plot and the Shapiro–Wilk test. The independent Of 68 patients assessed for eligibility, 66 patients were enrolled and randomly assigned to the study groups; 61 (92%) completed the study . The total administered dose of propofol was 18% lower in the lidocaine group, although this result was not significant (P = 0.085). In addition, the incidence of patient involuntary movement during the procedure was lower in the lidocaine group . Hemodynamics during the procedure was similar between the 2 groups   and selective depression of pain transmission through the spinal cord (reduction of postsynaptic depolarization mediated by N-methyl-D-aspartate and neurokinin receptors).19 The analgesic efficacy of IV lidocaine has been observed mostly in abdominal surgeries, including colectomy, gastrectomy, and cholecystectomy, with no evidence of efficacy during other surgeries, such as including tonsillectomy, total hip arthroplasty, or cardiac surgery.20 On the basis of these results, the analgesic effects of lidocaine are more potent for visceral pain than somatic pain. Pain during ESD is induced by overextension of the gastric wall and heat coagulation of the muscularis and post-ESD pain is caused by an inflamed artificial gastric ulcer and exposure to gastric acid.21 Therefore, we hypothesized that IV lidocaine would be beneficial for controlling visceral pain from ESD. As we predicted, administration of IV lidocaine during ESD resulted in less fentanyl consumption during ESD and reduction of epigastric pain intensity after ESD. The half-life of lidocaine is 1.5 to 2 hours following bolus injection or continuous infusion lasting less than 12 hours.22 Because of the short half-life of IV lidocaine, greater reduction in pain score has been reported in the earlier postoperative period when infusion was discontinued at the end of surgery.10 This may contribute to the reason why analgesic effect was noted at 6�hours but not at 24�hours in our results.IV lidocaine has been used for relieving chronic pain, such as from cancer and neuropathy.23 It is known that the addition of fentanyl can reduce the total dose of propofol, and consequently decrease the risk of rapid, irreversible oversedation, and respiratory events compared with propofol monosedation.24 However, fentanyl itself is also associated with a high risk of respiratory depression, which occurs in a dose-dependent manner and persists longer than the analgesic effect.25 Thus, fentanyl-sparing effect of IV lidocaine is meaningful for maintenance of the airway and spontaneous breathing in sedated patients. We found that desaturation incidence during ESD was similar between the 2 groups, even though more patients in the lidocaine group had a snoring history, which is an independent risk factor of respiratory events.24 In addition to its fentanyl-sparing effect, IV lidocaine has been shown to have a propofol-sparing effect during general anesthesia; this effect is mediated by an antinociceptive action rather than a hypnotic effect.26 Although not statistically significant, we found that the total propofol dose was 18% lower in the lidocaine group (P = 0.085), which is consistent with a previous report that lidocaine reduced the propofol requirement by 15% during thyroidectomy.26Fentanyl is the drug of choice for endoscopy because of its rapid onset, its minimal effect on the cardiovascular system, and its fast recovery time.15 Because administration of IV lidocaine as an adjunctive agent during ESD reduced the incidence of patient movements with less fentanyl consumption, it should be considered as an effective adjunctive agent for such patients.Addition of IV lidocaine was associated with significantly lower incidence of involuntary movements during ESD in this study. Patient movements usually interrupt the ESD process, which can lead to longer procedure time and possibly result in serious complications, such as bleeding or perforation. This lower incidence of involuntary movements may be due to a more consistent sedation level among the lidocaine group, even though the sedation depth was targeted at 3 or 4 on the MOAA/S scale for both groups. The American Gastroenterological Association recommends use of an adjunctive agent in combination with conventional sedation drugs for difficult-to-sedate patients.27 Although no prior studies reported throat pain after ESD, there is evidence that oropharyngeal mucosal injury is common during insertion of a transesophageal echocardiography probe (55%).28 Thus, we speculated that similar injuries can occur during insertion of a gastrointestinal endoscopy probe. Furthermore, to-and-fro movement of the endoscopy probe throughout the procedure may further worsen the injury. As sore throat is the source of dissatisfaction and discomfort after a procedure, more caution is needed during the manipulation of an endoscopy probe, and efforts to reduce throat pain with drugs should be taken.IV lidocaine reduced the incidence of throat pain from 65% to 27% in our study. A previous study found that IV lidocaine was effective in reducing postoperative sore throat caused by tracheal intubation.29 Toxic concentration of lidocaine (>5 μg/mL) has been reported after longer-duration lidocaine infusion during cardiac or abdominal surgery.12 However, a meta-analysis concluded that the incidence of adverse cardiovascular or neurological events did not increase with IV lidocaine infusion.12 A previous study showed that IV lidocaine as a bolus injection of 1.5 mg/kg at induction of anesthesia followed by a continuous infusion of 2 mg/kg/h during laparoscopic colectomy resulted in a plasma concentration of 2.7 ± 1.1 μg/mL by the end of surgery.14 In that study, bolus dose and infusion rate of lidocaine were the same as in our study. However, their anesthesia duration was longer (169 ± 47 minutes) than our procedure time (41 ± 14 minutes), leading us to assume that the plasma concentration of lidocaine in our patients was ≤2.7 ± 1.1 μg/mL.We did not observe any cardiovascular or neurological side effects associated with IV lidocaine. The clinically effective pain-relieving concentration of serum lidocaine is estimated to be 2 to 10 μg/mL, which is sufficient to reduce discharge of the peripheral pain-transducing nerves, A-δ, and C-fibers.A limitation of this study is the small number of patients, which restricts our ability to assess the safety of IV lidocaine for ESD. As our sample size calculation was based on the total administered dose of fentanyl during ESD, a larger-scale trial is needed to determine whether some patients with coexisting disease are more likely to develop toxicity.In conclusion, IV lidocaine administered as a bolus of 1.5 mg/kg and then as a continuous infusion of 2 mg/kg/h reduced fentanyl requirements and incidence of patient movement during ESD. It also lowered the severity of epigastric pain and the incidence of throat pain after ESD. As these beneficial effects were not associated with any adverse effects, IV lidocaine as an adjuvant with conventional sedation drugs should be considered as a new component of sedative medications for ESD.


Diabetic neuropathy is one of the chronic complications of hyperglycemia, which characterizes Diabetes Mellitus. As a result of an indolent course, the absence of signs and symptoms and nonspecific manifestations, it can remain undiagnosed for a long time. One of the clinical presentations is the presence of neuropathic symptoms, such as pain, cramps or paresthesia, which can compromise the quality of life.The objective of this study was to demonstrate that the pharmacological treatment of neuropathic pain can promote a significant symptomatic improvement assessed by validated scores and that the establishment of a support center in neuropathy constitutes an important measure in the context of multidisciplinary care of the diabetic patient.53 patients were recruited with a mean age of 58 yrs., similar gender distribution , mostly with type 2 Diabetes Mellitus (83%), average diagnosis time of 18 yrs. and median time for neuropathic symptoms of 2 yrs.At the first visit, subjects had pain intensity classified as moderate by the Analog Pain Scale, intensity of neuropathic symptoms classified as severe (56.6%) and neuropathic disability rated as moderate to severe impairment (41.5%). Following the prescription of specific pharmacological treatment, 91.6% of patients reported maintenance or improvement of symptoms and only 2.8% reported worsening. It was observed significant improvement in Neuropathic Symptoms Score (p=0.0006) and Analogic Pain Scale (p <0.0001), especially in type 2 diabetic group. There was no change in Neuropathic Disability Score.This study demonstrated that the existence of a support center for assessment and treatment of painful diabetic neuropathy in a Diabetes reference service allows early diagnosis and intervention in neuropathic symptoms in an effective way.


Neck pain is a common musculoskeletal complaint and is often associated with shoulder or arm pain. There is a paucity of information on effective treatment for neck and arm pain, such as radiculopathy or cervico-brachial pain. Guidelines recommend neck mobilisation/ manipulation, exercises and advice as the treatment for neck pain, and neck and arm pain. There are a few studies that have used neural mobilisation as the treatment for cervico-brachial pain. Although results seem promising the studies have small sample sizes that make it difficult to draw definite conclusions.A randomised controlled trial will be used to establish the effect of neural mobilisation on the pain, function and quality of life of patients with cervico-brachial pain. Patients will be recruited in four physiotherapy private practices and randomly assigned to usual care or usual care plus neural mobilisation.In clinical practice neural mobilisations is commonly used for cervico-brachial pain. Although study outcomes seem promising, most studies have small participant numbers. Targeting the neural structures as part of the management plan for a subgroup of patients with nerve mechano-sensitivity seems feasible. Patients with neuropathic pain and psychosocial risk factors such as catastrophising, respond poorly to treatment. Although a recent study found these patients less likely to respond to neural mobilisation, the current study will be able to assess whether neural mobilisation has any added benefit compared to usual care. The study will contribute to the knowledge base of treatment of patients with cervico-brachial pain. The findings of the study will be published in an appropriate journal.PACTR201303000500157.Trial registration Number: The online version of this article (doi:10.1186/1471-2474-15-419) contains supplementary material, which is available to authorized users. Neck pain is one of the most common debilitating musculoskeletal complaints seen in physiotherapy practice –3. In a Neck pain is often associated with headache, upper back and shoulder/arm pain , 6. In aNeuropathic pain is described as pain initiated or caused by a primary lesion or dysfunction in the nervous system . NeuropaPsychosocial factors have also been shown to play an important role in treatment outcomes –21. PoolMost clinical guidelines do not differentiate between treatment for neck pain and neck and arm pain such as cervico-brachial pain . The AmeNeural mobilisations (NM) are often used to affect the neural structures in conditions with signs of neural involvement or neural mechano-sensitivity , 11. NM The efficacy of NM has been studied in various populations such as low back pain , carpal The aims of the study are firstly to establish the effect of NM on the pain, function and quality of life of patients with acute and sub-acute cervico-brachial pain. Secondly it aims to establish if high catastrophising scores and neuropathic pain have an influence on treatment outcomes.A randomised controlled trial will be used to answer the research questions. The study will comprise of two groups, a control group and an experimental group. The control group will receive “usual care” (UC)  as identPatients will be recruited from private physiotherapy practices, which have agreed to take part in the study. These practices will be situated in the Pretoria region, Gauteng, South Africa. Patients are referred to private practices by general practitioners or may be self-referred. Patients presenting with cervico-brachial pain will be screened for eligibility and if eligible will be invited to take part in the study Figure .Figure 1To be included in the study patients must be over the age of 18, with cervico-brachial pain as defined by Hall and Elvey . PatientPatients who do not have a positive neurodynamic test will not be included in the study. Patients will be excluded from the study if they have had previous surgery or recent fractures of the cervical spine, serious neurological signs such as signs of spinal cord pressure or involvement of more than two nerve roots, conditions with long tract signs and those caused by other pathological diseases such as rheumatoid arthritis, neurological diseases, stroke, cerebral palsy, carcinoma or other red flags.Primarily this study sets out to assess whether, 6 weeks after onset of treatment the Numerical Pain Rating Scale NPRS score in the intervention group is reduced compared to the UC group. A blocked 2:1 ratio randomisation for intervention to usual care will be done using a computer generated random number list. A sample size of 68:34 i.e. a total sample of 102 patients will have 90% power to detect a clinically relevant increase of 2 for the change from baseline at six weeks in the NPRS score. A standard deviation of 2.05 was assumed as derived from the effect size reported by Bolton and Wilkinson . The staWritten consent to take part in the study will be obtained from all study participants and they will receive an information sheet explaining the study. Written consent will be obtained from treating physiotherapists. Ethical approval for the study was obtained from the Human Research Ethics Committee of the University of the Witwatersrand, Johannesburg, South Africa.The treating physiotherapist will administer the first set of questionnaires. Treatment randomisation will only be done as described above, after initial measures have been taken. All subsequent follow up questionnaires will be administered by a research assistant who will be blinded to group allocation as the follow up questionnaires at three weeks and six weeks will be done telephonically. The primary outcomes are pain , function  and quality of life . These self-report outcomes will be followed up at three weeks, six weeks, six months and 12 months.The NPRS will be used to measure the patient’s pain. The NPRS is an 11-point scale where patients are asked to rate their pain as 0 representing “no pain” and 10 “worst pain possible”. In a study comparing three pain measures . Bolton The Patient Specific Functional Scale (PSFS) will be used to measure disability. The PSFS is a self-report measure to rate activity limitation and function. Patients are asked to nominate three to five activities that are difficult to perform and rate them on an 11 point scale where 0 equals “unable to perform activity” and 10 represents “able to perform activity as before”. The scale was initially developed for patients with back pain and validated for patients with neck pain by Westaway et al. . The scaEuroQuol Instrument (EQ-5D) is a quality of life measurement and will be used to rate the quality of life of study participants. It has two sections: the first part consists of five sections namely mobility, self-care, usual activities, pain/discomfort and anxiety/depression. Each section is rated by three descriptions from “I have no problem” to “I am unable”. The second section of the questionnaire has a 20 cm Visual Analogue Scale with “best imaginable health state” at the one end and “worst imaginable health state” at the other end. The validity was established by measuring it against the SF-12 and positive correlations were found (r = 0.41). It has excellent reliability (ICC 0.82) . PeolssoPatients will be asked to complete the Global Rating of Change Scale (GROC) six weeks after treatment has commenced. This scale measures the patient’s impression of improvement after an intervention. According to a review there are eight different scales . In thisTwo questionnaires will be used to establish which patients have neuropathic pain and which patients are catastrophisers. These questionnaires will be repeated at six months and 12 months to measure if any change has taken place from initial assessment to one year follow up.The Neuropathic Pain Diagnostic questionnaire (DN4) consists of two sections namely an interview and examination. The interview has two questions, the first about the characteristics of the pain (e.g. burning) and the second about associated symptoms (such as pins and needles) to which the answer is either yes or no. In the examination, tests for hypoesthesia to touch and prick in the painful area as well as whether or not brushing aggravates the pain, are done. Each positive scores a point with a total score of 10. A patient with a score of 4/10 or more can be diagnosed with neuropathic pain . The senThe Pain Catastrophising Scale (PCS) is a questionnaire that establishes the levels of catastrophising present in patients. The questionnaire has three components: magnification, rumination and helplessness. Participants are asked to reflect on past painful experiences and to indicate the degree to which they experienced each of 13 thoughts or feelings when experiencing pain. It is scored on a 5-point scale from 0 “not at all” to 4 “all the time” with a maximum score of 52. A score above 24 classifies the patient as a catastrophiser . The intThe Upper Limb Neurodynamic Test 1 (ULNDT1) is described as the straight leg raise test of the arm . The uppFour physiotherapists in private practice (including the researcher) will be the treating physiotherapists. All the physiotherapists are qualified manual therapists with knowledge of neural mobilisations. All participating physiotherapists will take part in a training workshop run by the researcher. The training workshop will consist of: training of the application of neural mobilisation along the course of the nerve, protocol for treatment groups, outcomes measures, baseline measures as well as patient screening.The inter- and intra-rater reliability of the researcher and the research assistant was established for the ULNDT1. Inter-class correlation coefficient was good at 0.85, (95% CI 0.66-1.06). Intra-class correlation coefficient for physiotherapist 1: 0.85, (9 5% CI 0.64 -1.06) and for physiotherapist 2: 0.70 (95% CI 0.31- 1.09) which was acceptable.Patients presenting at participating physiotherapy practices with neck and arm pain will be screened for inclusion into the study. Suitable candidates will receive a full musculoskeletal examination to confirm that they comply with the criteria for cervico-brachial pain as described above . They wiPhysical examination will include the ULNDT1. The test will be done as described above . The ranBlock Randomisation with a 2:1 ratio in blocks of 6 will be done , 60. AccPhysiotherapists will receive an envelope with the patient information leaflet, consent form, treatment recording sheet and all questionnaires. Group allocation will not be visible and the research assistant doing follow up measurements will be blinded to group allocation. Treatment recording sheets will only be collected at the end of the data collection period. The treatment sheets will be used to assess whether treatment allocation was followed, number of treatment sessions and to screen for any adverse events due to treatment.The American Physical Therapy Association Guidelines  as well The UC will consist of mobilisation of the cervical and thoracic spine, exercises and advice to stay active. As most physiotherapists in South Africa have been Maitland trained, the patients will receive Maitland mobilisation  of the cThe intervention group will receive the NM in addition to UC. The NM used in this study will be done as described by Butler , a gentlPrimarily this study sets out to assess whether, six weeks after onset of treatment the NPRS score in the intervention group is reduced compared to the UC group. The sample size calculation is reported for the NPRS, which require the largest sample size.The data summary will employ descriptive statistics, means, standard deviations and 95% confidence intervals and will be reported by study group (intervention & standard care) for the NPRS, PSFS and EQ-5D. Catastrophising (yes & no) and neuropathic pain (yes & no) will be summarised using frequencies, percentages, cross tables and 95% confidence intervals.Two treatment groups will be compared with respect to the change from baseline at six weeks in the NPRS, PSFS and EQ-5D scores using an analysis of covariance (ANCOVA) with baseline scores, catastrophising (yes & no) and neuropathic pain (yes & no) as covariates. For the total assessment period of 12 months the interaction between visits and treatment will be assessed with respect to NPRS, PSFS and EQ-5D scores in a linear mixed model analysis. Testing will be done at the 0.05 level of significance. For all data description and analyses an intention-to-treat analysis will be performed.Evidence for the treatment of neck and arm pain (including radiculopathy) is sparse . In a reThe findings of this study should add to the knowledge base on the management of patients with cervico-brachial pain. Results of this study will be published in an appropriate journal.


To evaluate results of early tubal occlusions performed by hysteroscopy (Essure. This prospective study included 38 patients, 73.7% of them were white, mean age 34.5 years, they have had on average 3 pregnancies and 2.7 of deliveries. A total of 86.8% of patients previously prepared the endometrium. All procedures were carried out at outpatient unit without anesthesia Insertion rate of the device was 100% at a mean time of 4 minutes and 50 seconds. Based on the analogical visual scale, average pain reported was three, and 55.3% of women did not report pain after the procedure. After 3 months, 89.5% of patients were very satisfied with the method. Simple radiographs of the pelvis showed 92.1% of topical devices, and one case of unilateral expulsion had occurred. A four years follow-up did not show failure in the method. Tubal occlusion through hysteroscopy at outpatient unit and without anesthesia was a quickly and well-tolerated procedure. No serious complications were seen, the success rate was high, and patients were satisfied. This technique have been changed progressively by the introduction of minimally invasive surgery. In developing countries the minilaparotomy remains the most common procedure, but in developed countries interval laparoscopic sterilization is most the common technique.Female sterilization by tubal ligation or occlusion is the most effective and used method for family planning worldwide.Definitive and ideal contraceptive method would be highly efficient and cause minimal complications. Transcervical access constitutes an appealing alternative for transabdominal access, and it does not require incisions, general anesthesia, and avoids the risk of accessing the abdominal cavity. However, development of safety and effective transcervical methods seems to be difficult.Laparoscopic ligature is efficient, but invasive and with possible anesthesia and surgical risks, such as vascular and bowel injury.®, Bayer AG  was the first mechanical device approved in 2002 by Food and Drug Administration (FDA) for transcervical sterilization. This device was approved in 2009 by the Brazilian Health Surveillance Agency (ANVISA).EssureThe system includes an intratubal device, a release system and one catheter to access each tube by transcervical route. The microdevice is a dynamically expanding coil made up of internal ring of stainless steel involved by external ring made of nickel titanium, which expansiveness maintains the device into the uterine-tubal junction during the period required to occur the fibrosis. Polyester fibers are around the central structure and may cause reaction to surrounding tissue, followed by fibrosis, therefore, promoting an irreversible fallopian tube occlusion. This process occurs in approximately 3 months and, during this period, the woman must maintain the use of oral contraception.® system inside it during the hysteroscopy. Placement is considered successful when three to eight spirals remains visible in the uterine cavity.The device has 26 spirals with 4cm length and 0.8mm diameter, and it expands to 1 to 2mm in diameter. The insertion consists of catheter passing through the tubes with the EssureReview after implantation of the device is considered the final part of the procedure and three months are required before check if the implant is on the pelvis and at adequate position. In the United States, a hysterosalpingography (HSG) is requested, but in other countries a simple radiography of pelvis or ultrasonography is needed. If the device is satisfactory placed in uterine-tubal junction, the patient can stop the other contraception methods. If position is unsatisfactory, HSG is needed.® system showed efficacy of 99.74%.Most of gestation occurred because the patient did not follow medical guidance of use other contraceptive method for 3 months after placement or did not return to confirm the occlusion. There were also some mistakes in tests interpretation, and some patients were already pregnant at the time of placement.Veersema reports success in placement of 95% to 99% of cases at outpatient unit.Complications associated with the method are quite rare and include inadequate placement (poor placement), device migration, unintended pregnancies, pain, infection and nickel allergy. Uterine or tubal perforation can result in pregnancy or chronic pelvic pain.Because this is an irreversible method, the main contraindication is for patient who is unsure of definitive contraception. Other active or recent gynecologic infection, the malignant gynecologic tumor and current use of corticosteroids, if the medication cannot be stopped for 3 months. After delivery or pregnancy interruption a period of 6 weeks should be wait for insertion of the device.After 5 years, Essure® has the following advantages compared with laparoscopic tubal ligation: it does not require any incision, the insertion is done on an outpatient basis, it does not require anesthesia, time waste in the procedure is minimal, and patients are discharged immediately after the procedure and can return to daily activities on the same day after the placement.EssureTo evaluate acceptance of tubal occlusion method by hysteroscopy done on an outpatient basis without anesthesia, and also assess device insertion rate, time spend in the procedure, complications, pain after placement, time needed to return for normal activities, tubal occlusion rate, patient’s degree of satisfaction, pregnancy rate after 4 years of follow-up.Hospital do Servidor Público “Francisco Morato de Oliveira”. We included 39 patients. Of them, 73.7% were white with mean age 34.5 years, and have had on average 3 pregnancies and 2.7 deliveries. A total of 86.8% of patients had previously prepared the endometrium. Patients included chosen definitive contraceptive method after receive information about other options/methods at Family Planning Sector. All patients were informed about available methods of tubal occlusion . Those who decided to do the latter method signed the consent form. This study was approved by Institutional Ethics and Research Committee, number CAAE: 0095.1.338.000-10.This prospective study was carried out from February 2009 to July 2010 at the hysteroscopy unit of the All patients received anti-inflammatory drugs (Ibuprofen 600mg) and benzodiazepines drugs (diazepam 10mg) one hour before the procedure to avoid spasm of uterine tubes.® system inside it. This catheter is introduced through (1.7mm) operative channel 5F of Bettocchi® hysteroscopy . We used saline solution for uterine distension, and no anesthesia during the procedure. The procedure was carried out in first phase of the cycle or during the use of contraceptive drugs, for good visibility of uterine cavity and tubal ostiums. Those procedures performed during the use of levonorgestrel intrauterine system did not show any additional difficult because this device does not prevent tubal catheterization.Device insertion occurred during ambulatory hysteroscopy beginning with vaginoscopy, without the use of speculum or Pozzi forceps to traction the cervix. The procedures entails catheter passing through the tubes with the Essure Because this procedure recovery is immediately, no resting was need after the procedure at the outpatient unit.Pain was evaluated by patients immediately after the device placement based on Visual Analogue Scale (VAS). This measure comprised of line of 10cm with anchors in both extremities. One extremity is identified as “no pain”, and the other “pain as bad as it possibly be”. This instrument has been considered sensible, simple, reproducible and universal.After 30 days, in the first return consultation, patients reported the presence or absence of pain just after the hysteroscopy and in the subsequent days, in addition, they also reported time needed to return to daily life activities.® insertion, a simple radiographic of pelvic region was done. If the device was satisfactory placed in the uterus – tubal junction, the occlusion was considered definitive. If the position was unsatisfactory, an HSG was requested. At this time, patients’ satisfaction with the method was assessed. Four years after insertion, the investigator called patients to collect information about possible failures of the method. Variables included were age, number of pregnancies, parity, type of delivery, formal education, endometrial preparation, pain during and after the procedure, duration of the procedure, time needed to return to daily activities, satisfaction with the method, position of the device on simple radiographic of the pelvis and presence of tubal occlusion in the HSG.After 3 months of EssurePain during the procedure was stratified into three categories: 0 to 4 , 5 to 7 (moderate pain) and 8 to 10 (intense pain). All information and results were analyzed using the statistical software Epi Info™ 3.5.2 for Windows, with descriptive calculation of mean and standard deviation for quantitative variables and frequency of qualitative variables. Univariate analysis was done using the Pearson’s correlation test. The p<0.05 was considered statistical significant in a confidence interval of 95% (95%CI).We included 38 patients with mean age 34.5 years, and 73.7% of participants were white. Of them, 28.9% had finished elementary school, 39.5% had attended high school, and 31.6% graduated from college. Number of pregnancies ranged from one to nine, mean of three gestations, and mean of 2.7% deliveries.A total of 86.8% of patients had previous endometrial preparation. Of them, 78.8% used oral combined contraceptives, 15.2% used oral progestogen, and 3.0% used combined injectable contraceptives. Only one patient used the levonorgestrel intrauterine system. Endometrial preparation did not change the time required for the device placement.All devices were successful placed bilaterally, procedural time was on average 4.5 minutes. Pain scale ranged from zero to 10, mean of three. Patients reporting no pain or mild pain were 68.4%, 23.7% reported moderate pain, and 7.9% reported intense pain. There was no association between pain scale and formal education, type of delivery, time required for the device placement, however, a correlation was seen related to the number of pregnancies and deliveries .One patient had vagal reflex that stopped rapidly after the use of sublingual atropine. No pain after the procedure was reported by 55.3% of patients. Among those who remained in pain, 39.5% reported pain lasting for 2 days and, in 5.3% the pain lasted for more than 2 days.Time to return for daily activities ranged from zero to 5 days, and 89.5% of patients returned to daily routine on the same day. At return consultation, after 3 months, 89.5% of patients were very satisfied, 10.5% were satisfied and no patient was disappointed with the method.® localization, and the HSG showed bilateral tubal obstruction in 75% of patients. In one case, we observed unilaterally patent tube because of the device migration to the pelvis. After 4 years of sterilization, no failure to prevent pregnancy was reported.Radiographies showed that 92.1% of devices were topic and tubes were considered obstructed. In 7.9% of cases there were uncertainty about Essure® is a new method in Brazil, more than 750,000 woman worldwide are using this method, which cause a conceptual revolution in permanent birth control procedure.Although Essure In our study success rate was 100%, probably because of our small sample.Success rate in first attempt of insertion reported by many authors ranges from 81 to 98%.,6The main reasons of non-insertion of a device are poor visualization of ostiums, and when the procedure is done in first phase of menstrual cycle or previous endometrial preparation with hormones. We attempted to prevent tubal spasm before the procedure based on report of a number of authors by using anti-inflammatory drugs and benzodiazepines.. Pain is the main concern of patients, we used the same approach described by Veersema, which is previously inform that discomfort would be similar to menstrual cramps, this information helped patients to become less concerned.All procedures were carried out at the outpatient units. Evidences show that efficacy is the same when compared to procedures performed at surgical centerAccording to Veersema, pain is related to duration of the procedure. The procedures last, on average, for 4 minutes and 50 seconds, which probably cause high tolerability and patients’ satisfaction.Vaginoscopy technique used in all cases along with low diameter of optics have caused lower discomfort for patients, not requiring the use of anesthesia. The vaginoscopy was not used, and mean pain reported was 3.0, based on a visual analogical scale from zero to 10cm. Previous studies in hysteroscopy at outpatient unit showed pain ranging from 3.2 to 4.7, using the same pain scale.The complication of the procedure was vagal reflex (2.6%). Other studies reported 3.7% of same reaction, but recovery was immediate after use of atropine.Arjona et al. carried out 1,630 procedures at outpatient unit without anesthesia, and 80% of women returned to daily activities on the same day. In our study 89.5% of participants returned to daily activities on the same day.® from uterine cavity and one bilateral migration of the device to pelvis, which was identified and removed during laparoscopic tubal ligation. Migration of the device for pelvic cavity is rare, its incidence reported is 0.1%.,10Simple pelvic radiography was used as the control test 3 months after the procedure. In three cases, because of uncertainty of correct positioning, the HSG was done. In one case, there was migration unilaterally of the device to pelvis, being the device removed through laparoscopy. Aparicio-Rodríguez-Miñon et al. studied 517 patients and found two expulsion of Essure,10All patients completed the 3 months follow-up. When patients was inquired about satisfaction with the method, 89.5% were very satisfied, 10.5% satisfied, and no patient was disappointed with the method. Another study evaluated satisfaction rate during return consultation after 3 months and described that 94% of patients were very satisfied with the procedure, 6% had some type of satisfaction and no patients were dissatisfied.® placement as almost inexistent. No patients in our study get pregnant after a 4 year follow-up.Recent literature reviews show unintended pregnancy rate after EssureTubal occlusion by hysteroscopy at outpatient unit and without anesthesia was a quick and well-tolerated procedure. We did not observe severe complications. Success rate and patients’ satisfaction were high.


Introduction. Pain syndromes affect women after conservative and radical breast oncological procedures. Radiation therapy influences their development. We report autologous fat grafting therapeutical role in treating chronic pain in irradiated patients. Materials and Methods. From February 2006 to November 2014, we collect a total of 209 patients who meet the definition of “Postmastectomy Pain Syndrome” (PMPS) and had undergone mastectomy with axillary dissection (113 patients) or quadrantectomy (96 patients). Both procedures were followed by radiotherapy. We performed fat grafting following Coleman's procedure. Mean amount of adipose tissue injected was 52 cc (±8.9 cc) per breast. Seventy-eight in 209 patients were not treated surgically and were considered as control group. Data were gathered through preoperative and postoperative VAS questionnaires; analgesic drug intake was recorded. Results. The follow-up was at 12 months (range 11.7–13.5 months). In 120 treated patients we detected pain decrease . Forty-eight in 59 patients stopped their analgesic drug therapy. Controls reported a mean ± SD decrease of pain of 1.14 ± 2.72. Results showed that pain decreased significantly in patients treated . Conclusion. Our 8-year experience confirms fat grafting effectiveness in decreasing neuropathic pain. Chronic pain affects from 25% to 60% of women submitted to breast surgery, both mastectomy and conservative procedures for oncological reasons, and represents an important clinical problem involving intra- and postoperative factors .This condition, also named Postmastectomy Pain Syndrome (PMPS), is situated in the anterior side of the thorax, in the axilla, and/or in the upper half of the arm and lasts more than 3 months after mastectomy or quadrantectomy surgical procedures .Several risk factors have been advocated to explain the development of PMPS  such as Moreover, BMI, age, and physiological status could also be a predictive factor in postsurgical pain .Beyond all these multifactorial risk factors, radiotherapy strongly influences the development of PMPS as already noted by Tasmuth et al. .Medications commonly used to treat nociceptive pain, such as opioids, have proved to be ineffective for neuropathic pain and a chronic analgesic therapy is burdened with complications and high rate of drop-off.In our experience, autologous fat graft obtained following Coleman's technique has proven to be an efficient and safe procedure in treating the clinical field of breast reconstructive surgery, providing an important tool for correction of breast size and shape.In 2006, our group started treating patients submitted to mastectomy with axillary dissection and radiotherapy  demonstrIn both groups we observed a significant decrease in pain after procedure and a reduction of intake of analgesic drug therapy.The present review aims to report our experience in treating chronic pain in irradiated breasts collected after an 8-year experience confirming autologous fat grafting role in improving pain control in patients affected by PMPS.From February 2006 to November 2014, a total of 209 patients who had undergone mastectomy with axillary dissection (113 patients) or quadrantectomy (96 patients) came to our Institution.Both procedures were followed by radiotherapy for oncological reasons.We selected patients who presented severe scar retraction, radiodystrophy, and chronic pain meeting the definition of “Postmastectomy Pain Syndrome.”All patients enlisted had a normal follow-up with no complications, such as dehiscence, infection, or scar anomalies.In our study population, we performed autologous fat grafting following Coleman's procedure. After routine preoperative examination and clinical assessment, patients underwent liposuction of the subumbilical area under sedation and local anesthesia. The adipose tissue was harvested from abdominal subcutaneous fat which is an easy accessible and abundant reservoir.The fat graft was injected using 18-gauge angiographic needle with a snap-on wing  at the dermohypodermal junction in the painful and radiodystrophic scar areas. The mean amount of adipose tissue injected was 52 cc (±8.9 cc) per breast. In particular, in patients submitted to mastectomy, mean amount of adipose tissue was 55 cc (±9.3 cc) per breast, while in patients submitted to quadrantectomy mean value was 39 cc per breast (±5.4 cc).Seventy-eight in 209 patients with Postmastectomy Pain Syndrome (41 submitted to mastectomy and 37 to quadrantectomy) not treated surgically were considered as a control group for statistical analysis.Patients were assigned to control group due to their refusal to be submitted to surgical procedure, although they present comparable VAS scores.During the first visit, a trained research assistant explained the purpose and methods of this study to each eligible patient; patients who were willing to participate signed an informed agreement.Data were gathered through preoperative and postoperative questionnaires.Before undergoing the surgical procedure, patients were required to score their spontaneous pain using a visual analogue scale ranging from 0 to 10; analgesic drug intake was also recorded.During follow-up patients were required to fill out the same questionnaire and possible modification in analgesic intake was also accurately recorded.We collected a total of 209 patients; 113 patients were submitted to mastectomy with axillary dissection, while 96 patients were submitted to quadrantectomy.In our population we lost a total of nineteen patients in the follow-up .In 120 treated patients we observed a mean VAS before fat grafting of 7.2 (SD ± 2.1) and a value of 3.3 (SD ± 3.1) after treatment so that we detected a mean pain decrease of 3.19 (SD ± 2.86).This effect has been observed since two weeks from the procedure.In the treated group a total of 48 patients stopped their analgesic drug therapy.In this group mean VAS before fat grafting was 7.7 (±2.7) and 3.4 (±2.4) after autologous fat grafting; thus the mean pain decrease was 4.23 (SD ± 2.14).In the group of patients that continued analgesic therapy mean VAS before treatment was 7.9 (±1.9), while after treatment mean value was 4.2 (±2.3) with a mean pain decrease of 1.15 (SD ± 2.79).Control group at first outpatient visit showed a mean VAS of 6.9 (±2.2), while at follow-up visit they showed a mean VAS of 5.8 (±1.9) reporting a mean pain decrease of 1.14 (SD ± 2.72).Statistical analysis of the difference between VAS values was made before and after treatment in case patients and at first outpatient visit and at follow-up for controls. In both groups the follow-up was at 12 months (range 11.7–13.5 months).p < 0.005.Wilcoxon rank-sum test was employed with a level of significance fixed at p < 0.005), while in control patients no statistical difference was found (p > 0.05).Results showed that pain decreased significantly in patients with Postmastectomy Pain Syndrome treated with autologous fat tissue grafting , in the latter a statistical significant difference was observed (p < 0.005). By performing this test selection bias was excluded. Results are listed in In addition to that we compared VAS values in case patients before treatment with control patients at first outpatient visit. Eventually we compared again VAS values in case patients after treatment with control patients at follow-up visit. Mann and Whitney test was employed with a level of significance fixed at Persistent pain as a consequence of surgical treatment has been established for several common surgical procedures and represents a clinical problem of great magnitude.Postmastectomy Pain Syndrome was firstly reported in the 1970s by Wood . SubsequIn patients submitted to quadrantectomy or mastectomy, it presents common features and for this reason it is considered as a unique pathological condition characterized by a dull, burning, and aching sensation exacerbated by movement of the shoulder girdle .Women affected by PMPS may present signs and symptoms such as neck pain, shoulder pain, reduced mobility, and bad body image, demonstrating a multidimensional character that affects psychological and physical aspects of the patient's life .Though the exact pathogenesis of PMPS remains unclear, many etiological theories have been postulated.During the surgical procedure, dissection of the intercostobrachial nerve or damage of axillary nerve pathways could favor development of chronic pain after mastectomy or quadrantectomy. For this reason, chronic pain has a greater rate of occurrence in patients who underwent axillary lymph node dissection .Chemotherapy agents, such as taxanes, platinum agents, and vinca alkaloids, are neurotoxic, while endocrine therapy may induce musculoskeletal pain and arthralgia .Another possible explanation seems to be related to the scarring process which leads to fibrosis, strong adherence to the deeper muscular layer, and possible nervous entrapment which would represent a continuous trigger of nerve excitation. For this reason, postsurgical complications , 14 suchRadiation therapy represents a major risk factor for developing of PMPS since it leads to an inflammatory reaction accompanied by increased production of proinflammatory cytokines, such as IL-1, IL-6, TNF-alfa, and TGF-beta, and chemokines such as IL-8 and eotaxin. This inflammatory reaction can induce peripheral and central sensitization with a failed nociception system leading to pain augmentation. In addition to that, radiotherapy stimulates local fibrosis which could result in a strong adherence to the deeper muscular layer, sustaining a painful syndrome.Actually, the mainstay of treatment for PMPS as any form of neuropathic pain is pharmacological, including the use of antidepressants , antiepiOur group firstly proposed autologous fat graft as an effective complementary approach to relieve PMPS. Moving from the experience of Rigotti et al.  who treaIn our previous researches, histological proofs –19 have We have also hypothesized that autologous fat graft could induce molecular changes in the microenvironment of posttraumatic scar , which iIt is possible to hypothesize that fat grafting in PMPS induces analgesia by inhibition of inflammation. It is relevant to notice that mesenchymal stem cells could also downregulate radiation therapy induced inflammatory response as they inhibit production and release of proinflammatory cytokines, which are the main mediators of radio-induced tissue damage.In the present review we report our 8-year experience in treating Postmastectomy Pain Syndrome with autologous fat grafting in patients submitted to mastectomy with axillary dissection and quadrantectomy and radiotherapy.We considered patients affected as a unique study population as they all meet the definition of Postmastectomy Pain Syndrome.The main limitation of this study is the fact that we did not consider the placebo effect to give further strength to our protocol.In addition to that our research's lack of data regarding patients' age, BMI, and estrogen status as increasing evidence seems to correlate these variables to clinical outcome .Comparing data with a wide study population of 120 patients, to our knowledge the largest study population presented in a scientific report about this condition, we confirm autologous fat grafting's promising therapeutic role in the treatment of Postmastectomy Pain Syndrome.Fat graft has already proven its effectiveness in terms of pain decrease in the treatment of different forms of neuropathic pain as a result of its effect of scar entrapment release and anatomical remodeling.Because of its safety, efficacy, and optimal tolerability, we support its adoption as a standard procedure in each Breast Unit in patients who report chronic pain after breast surgery especially if previously submitted to radiotherapy.


One hundred sixty-one children were included in two subgroups: 4–8 years, average age 6.4 years, treated with verum or placebo and 6 months–<4 years, average age 1.8 years, treated only with verum. Pain reduction was measured from the time prior to administration to 10 or 30 minutes after. In addition, adverse events and local tolerability were evaluated. In group I, pain was reduced significantly after treatment with verum compared to placebo at both time points. In group II, the individual pain rating shift showed statistically significant lower pain after treatment. Only seven out of 161 patients reported an adverse event but none were classified as being related to the study medication. The local tolerability was assessed as very good in over 97% of cases. For painful sites in the oral cavity, a 2% lidocaine gel is a meaningful tool for short-term treatment in the paediatric population.Lidocaine is a well-accepted topical anaesthetic, also used in minors to treat painful conditions on mucosal membranes. This randomized, double-blind, placebo-controlled study (registered prospectively as EudraCT number  The use of medicinal products in younger children, even if approved and accepted for decades in adults and older children, often takes place with some uncertainties on the parents' or physician's site. Younger patients not only are smaller and have less weight but also have at least partly different pharmacokinetic characteristics . AlthougClinical trials according to accepted rules represent the highest standard of clinical evaluation to prove efficacy and safety but are difficult to perform in younger patients for various reasons . EthicalPain perception shows a high degree of individual variation in intensity, onset, and degree of toleration . In patiLidocaine is a well-established and approved local anaesthetic alone and in combination used in a variety of topically applied preparations, mostly as medicinal product . It is aThe objectives of this randomized, double-blind, placebo-controlled, phase IV study were to determine the efficacy and safety of a gel with 2% lidocaine in children from 6 months up to 8 years with painful conditions in the oral cavity as a meaningful tool for short-term treatment in the paediatric population. The verum preparation used is available in Germany for short-term, symptomatic treatment of pain on the oral mucosa, on the gums, or on lips. The dosing recommendation for children is up to 4 times daily as a pea size piece of gel (approximately 0.2 g gel or 4 mg lidocaine hydrochloride).2011-005336-25) was initiated after approval by the responsible ethics committee of the Medical Chamber of the German Federal State of Thuringia and by the German National Health Authority (BfArM). The study was conducted in accordance with the World Medical Association Declaration of Helsinki 2013, the Guidelines of ICH Good Clinical Practice (GCP) as well as the requirements of German national drug and data protection laws.This randomized, double-blind, placebo-controlled, single-centre, phase IV clinical trial  were included. Children with painful site/s in the oral cavity aged 4 years or older were randomly assigned to be treated either with verum or with placebo, whereas children younger than 4 years were only treated with verum.The 2% lidocaine gel  and the placebo preparation  were locally applied once by or under supervision of a member of the study staff to the painful site/s as a pea size amount of gel (0.2 g gel) corresponding to 4 mg lidocaine hydrochloride in case of verum.The whole study took place at a clinical trial facility, specialized in conducting clinical studies with children. Different patient recruitment arrangements, like advertisements in the local newspaper, referrals by paediatricians, and distribution of flyers, were performed to enlarge the number of suitable patients, after obtaining approval by the ethics committee and health authority.The painful sites were defined as open breaks of the oral mucosa, lips, or tongue as a symptom of a variety of mild diseases, or trauma, for example, bites, aphthous ulcer, mouth blisters, cold sores, partial gingivitis, hand-foot-mouth disease, herpes simplex, teething, and trauma from dental braces.The primary efficacy variable was the pain reduction from T1 (prior to administration) to T2 (10 ± 5 min after application) as assessed by the Wong-Baker FACES Pain Rating Scale . This scA secondary efficacy variable was pain reduction from T1 (prior to administration) to T3 . This “mixed” analysis of children's and parents' assessments was performed to consider the child's assessment as often as possible according to the protocol and statistical analysis plan (SAP). To investigate whether this approach was reliable, an additional analysis was performed with assessments of the same person , or parent, if the child's assessment was missing at one or two points of time). Additionally, assessment of satisfaction  and assessment of local tolerability by the investigator  were evaluated.Sample size calculation was performed within a parametric test scenario. In age group I, a sample number of 64 subjects per treatment arm was considered sufficient to obtain reliable data . For age group II, a sample size of 32 patients was chosen. In order to recruit 160 evaluable patients, about 222 subjects were planned to be screened, due to an assumed screening failure rate of 15% and a drop-out rate of 15%.The statistical analysis was conducted in compliance with the ICH E9 Note for Guidance on Statistical Principles for Clinical Trials.U test (differences between groups) and the Wilcoxon test , whereby the null hypothesis of no difference between both groups was tested. To evaluate the robustness of results, additional analyses were applied . All analyses were performed using Statistical Analysis System software, version 9.2 or higher .The efficacy variables were analysed by using the Mann-Whitney Study data were collected between May 21st, 2012, and June 14th, 2014, from 129 patients (age group I) and additional 32 patients (age group II). Within age group I, 63 patients were treated with 2% lidocaine gel (verum) and 66 patients with placebo. No patient dropped out of the study .N = 30, placebo N = 24) and 75 female subjects  were included. In age group II, both genders were equally distributed . The average age in group I was 6.4 ± 1.4 years, ranging from 4.0 to 8.9 years. In age group II, the mean average age was 1.8 ± 0.9 years, ranging from 6 months to 4.0 years. Except for one Black and one Latvian-Korean patient, all other patients were Caucasians.In age group I, 54 male (verum In age group I aphthous ulcer (36.0%) and in age group II teething (63.6%) were the main cause of painful sites .2, ranging from 5 mm2 to 150 mm2. Gingiva and/or oral mucosa were affected in the majority of cases , whereas lips or tongue were involved in the remaining cases. The parents in age group I often reported grouching (20.2%), changes in behaviour (24.1%), and poor feeding (26.0%), whereas in age group II weeping (14.2%), crying (13.5%), grouching (18.4%), and sleepiness (18.4%) were often reported.The mean average size of the painful sites was 19.9 ± 15.7 mmN = 53, placebo N = 54) at T1 (prior to administration) and in 109 cases  at T2 (10 ± 5 min after application). The assessments by parents were used in 22 cases at T1 and in 20 cases at T2, because of children's lack of ability to rate their pain properly or showing signs of unwillingness or lack of concentration.The self-rating by the children of age group I could be used in 107 cases  at T3. The assessments by parents were used for 21 patients at T3.For the secondary efficacy parameter (change of pain rating from T1 to T3 (30 ± 10 min after application)), the self-rating by the children was analysed in 108 patients (verum U test) of treatment related difference in pain assessment yielded a statistical significance (p < 0.001) of the observed effect in favour of the 2% lidocaine gel (verum). A similar result (p < 0.002) was achieved also for the measurement of pain reduction from T1 to T3. These results were reassured also if the assessment of the same person (either child or parent) was evaluated at both endpoints.On average (median) pain has been reduced by 2.0/5 (verum) versus 1.2/5 (placebo) . Nonparaα = 0.05 level .The children's satisfaction as assessed by parents on a 5-point verbal rating scale one hour after administration tends to yield a higher proportion of verum patients showing satisfaction, although observed differences compared to placebo arm did not reach a statistical significance at p value < 0.0001 and T3: p value < 0.0001).Age group II (aged <4 years) patients were all treated with lidocaine 2% gel (verum). In order to assess the efficacy, the individual shift in pain rating had been evaluated. There were no patients with a worsening of pain, 4 patients (12.5%) without a change, 13 patients (40.6%) with an improvement of one, 7 patients (21.9%) of two, 5 patients (15.6%) of three, and 3 patients (9.4%) of four categories in pain rating on T2 compared to T1 . This imSeven out of 161 patients (4.4%) reported in total 7 adverse events . Two adverse events were registered in each treatment arm in age group I and three adverse events in age group II after verum application (no placebo patients treated). None of these adverse events were assessed as related to study drug.For most patients  the local tolerability has been rated as “very good.”In general, clinical studies with younger patients are more difficult to conduct not only because of the regulatory situation, but also because of the lower motivation of the children and their parents to participate and less ability of the young patients to understand the study principles , 5. For Most children aged 4-5 years or older can provide meaningful self-reports of pain intensity, depending on training and provision with age-appropriate tools. Children younger than 4-5 years have a tendency to use only the extremes of a scale. Other response sets or biases include giving the same answer to all questions and responding in an upward or downward sequence to successive questions. Pain rating may be affected by their perception of the consequences of the rating, for example, reward for being brave and fear of getting a syringe. Many other cognitive, social, and cultural factors influence pain ratings  making them idiosyncratic and difficult to interpret . The assTopically applied locally acting medicinal products are more difficult to investigate than systemically acting products. Self-healing properties and placebo effects are presumably higher. For local skin or mucous membrane defects, the placebo formulations by themselves may have a healing or protecting effect.To solve these and other obstacles, we performed this study in a clinical trial facility and not in private practices, made sufficient patient enrolment possible with a variety of recruitment arrangements, excluded younger patients from the possibility to receive a placebo, and used an accepted pain rating scale for children, the Wong-Baker FACES Pain Rating Scale . The parMore than 80% of children in group I (4–8 years) were able to rate pain by themselves whereas for the remaining children self-reporting could not be used. It is interesting that on average children in this age group rated their pain slightly lower than their parents. However, it should be realized that comparing the child's face with the expression on the faces picture is indirect rating and may be sensitive to bias. As expected and anticipated in age group II mostly only the parents' assessment of how they consider the level of the children's pain before and after administration could be evaluated. These children were too young to allow the use of the pain scale.The medicinal product used in this study is authorized and on the market in Germany and France for many years. In Germany, it can be applied to children without age restriction. In a recently published clinical study in patients between 6 years and 15 years with pain because of clamp placement, oral trauma, or aphthous ulcers, the identical medicinal product  showed significant superiority compared to the respective placebo formulation . In the Lidocaine alone or in combination with another local anaesthetic is a well-known product for local pain reduction , 12. In Seven out of 161 subjects (4.4%) reported in total 7 adverse events . None of these adverse events were assessed as study drug related, clearly demonstrating the safety of the product.The 2% lidocaine gel, as successfully tested in our clinical trial in comparison to a placebo gel with the same composition without lidocaine, is an adequate tool to reduce or prevent pain on the oral mucosa or gingivae, like bites, aphthous ulcers, mouth blisters, cold sores, gingivitis, hand-foot-mouth disease, dental braces, or teething in younger children.


Kampo medicine, traditional Japanese herbal medicine, are used in our daily clinical practice. Pain is essentially an interactive psychophysiological behavior pattern. Thus, an interdisciplinary approach is often recommended in providing appropriate therapeutic care for the patients suffering from chronic and intractable pain. In addition, we have been prescribing Kampo medicines in combination with Western medicines as personalized medicine in order to treat patients with chronic pain at our pain center. The aim of our study was to conduct a survey on the current use and the effect of Kampo medicines in our multidisciplinary pain center.The Japanese medical system is unique because it is the only country in the world where Western medicine and traditional Japanese medicine including Retrospective analysis was performed on 221 out of 487 patients suffering from chronic pain.The most frequent medical complaints for which Kampo medicines were prescribed were lower back/lower limb pain, neck/upper limb pain, various facial pains, headache/migraine, whiplash-associated disorder, and frozen shoulder. Kampo medicines were prescribed based on patient-centered Kampo diagnosis. Moreover, several Kampo medicines generally for the management of psychological symptoms were prescribed for about 70% of the patients. Pain improvement in the patients was categorized as follows: 26.3% with marked improvement, 12.7% with moderate improvement, 38.9% with some improvement, and 19.9% with no improvement.Two thirds of the chronic pain patients with the use of Kampo medicines combined with Western medicine experienced further pain improvements. Kampo medical care at the same time in the same medical institution [Traditional, complementary, and alternative therapies are widely used and researched in the USA and Europe ,2. One otitution ,2. Kampotitution . The Mintitution . CurrentPain is essentially an interactive psychophysiological behavior pattern, so an appreciation of the biopsychosocial model is essential for understanding and caring for patients with chronic pain. Thus, an interdisciplinary approach is often recommended and considered to be extremely relevant in providing appropriate therapeutic care for patients suffering from chronic and intractable pain . Our cenRetrospective analysis from August 2012 to July 2013 was performed on 487 patients suffering from chronic pain who visited the pain center of Aichi Medical University Hospital. All patients were referred from other hospitals to the pain center. Patients who were prescribed Kampo extract formulations were included.After obtaining approval from the Ethics Committee of Aichi Medical University  and written informed consent, we routinely recorded demographics, symptoms, and course of pain in all patients. The intensity of pain was rated by the patients using a numerical rating scale (NRS) where 0 indicated no pain and 10 the greatest pain possible. All demographic and clinical data were extracted from medical records from August 2012 to March 2014 for the present study. In addition, patients were categorized as having marked improvement , moderate improvement , some improvement , and no improvement  depending on the state of pain improvement 6 months to 1 year after the initial visit. Moreover, patients who did not visit the hospital again even with an appointment for a follow-up visit and who visited the hospital for the purpose of receiving a second opinion were categorized separately.n = 81), neck/upper limb pain , various facial pains , headache/migraine , whiplash-associated disorder , and frozen shoulder . Pain improvement in all the patients who were prescribed Kampo medicines was categorized as follows: 26.3% with marked improvement, 12.7% with moderate improvement, 38.9% with some improvement, and 19.9% with no improvement. Table We administered treatment after a medical conference attended by different types of professionals . As required at the medical conference, we administered pharmacological (including Kampo medicine), physical, acupuncture, cognitive-behavioral, psychoanalytic, and psychological treatment. Kampo medicines were prescribed for 221 patients out of a total of 487 patients based on patient-centered Kampo diagnosis  while coGoshajinkigan , Shakuyakukanzoto , Yokukansan , Keishikajutsubuto , Hachimijiogan , and Juzentaihoto  for the management of lower back/lower limb pain. Pain improvement in the patients who were prescribed Kampo medicines was categorized as follows  of pain duration, 24 (3–320) months) was categorized as follows: 19.1% (n = 26) with marked improvement, 6.9% (n = 9) with moderate improvement, 12.5% (n = 17) with some improvement, and 25.0% (n = 34) with no improvement.Table nzoto 17.%, n = 14Keishibukuryogan , Yokukansan , Jidabokuippo , Tokishakuyakusa , Kamishoyosan , Kakkonto , and Kososan  for the management of neck/upper limb pain. Pain improvement in the patients who were prescribed Kampo medicines was categorized as follows  of pain duration, 24 (3–168) months) was categorized as follows (Table n = 13) with marked improvement, 9.2% (n = 6) with moderate improvement, 13.8% (n = 9) with some improvement, and 26.2% (n = 17) with no improvement.Table n = 13), Yokukansan , Maobushisaishinto , Keishibukuryogan , and Goreisan  for the management of various facial pains. Pain improvement in the patients was categorized as follows (Table Table n = 5), Kamishoyosan , Goshuyuto , and Jidabokuippo  for the management of headache/migraine. Pain improvement in the patients who were prescribed Kampo medicines was categorized as follows  of pain duration, 42 (3–240) months) was categorized as follows: 25.0% (n = 5) with marked improvement, 10.0% (n = 2) with moderate improvement, 10.0% (n = 2) with some improvement, and 15.0% (n = 3) with no improvement.Table n = 8), Keishibukuryogan , Tokishakuyakusa , Maobushisaishinto , and Yokukansan  for the management of whiplash-associated disorder. Pain improvement in the patients who were prescribed Kampo medicines was categorized as follows  of pain duration, 18 (3–144) months) was categorized as follows: 8.3% (n = 1) with marked improvement, 16.7% (n = 2) with some improvement, and 33.5% (n = 17) with no improvement.Table Nijutsuto  and Keishikajutsubuto  for the management of frozen shoulder. Pain improvement in the patients was categorized as follows , neck/upper limb pain , various facial pains , headache/migraine , whiplash-associated disorder , and frozen shoulder . In fact, we had these cases in the same order in our center and Kampo medicines were prescribed when treatment with Western medicine alone was insufficient. And this survey shows that the use of Kampo medicines combined with Western medicine as an interdisciplinary approach provided some improvements for two thirds of these patients refractory to Western medicine alone.The results of the present survey showed that Kampo medicines were prescribed to treat lower back/lower limb pain (36.6%, Goshajinkigan, Shakuyakukanzoto, Yokukansan, Keishikajutsubuto, Hachimijiogan, and Juzentaihoto were the most frequently prescribed Kampo medicines for lower back/lower limb pain. Goshajinkigan, Shakuyakukanzoto, Keishikajutsubuto, and Hachimijiogan have been used since ancient times to treat melosalgia, low back pain, and numbness -11. YokuKeishibukuryogan, Yokukansan, Jidabokuippo, Tokishakuyakusa, Kamishoyosan, Kakkonto, and Kososan were the most frequently prescribed Kampo medicines for neck/upper limb pain. Keishibukuryogan, Yokukansan, Tokishakuyakusa, Kamishoyosan, Kakkonto, and Kososan have been used for the management of headache and chronic neck pain ,9,13,14.Kamishoyosan, Yokukansan, Maobushisaishinto, Keishibukuryogan, and Goreisan were the most frequently prescribed Kampo medicines for various facial pains. Keishibukuryogan, Kamishoyosan and Yokukansan have been prescribed to manage emotional distress, headache, and clenching or grinding of the teeth ,9,12-14.Keishibukuryogan, Kamishoyosan, Goshuyuto, and Jidabokuippo were the most frequently prescribed Kampo medicines for headache/migraine. Goshuyuto has been used since ancient times to treat a very severe headache accompanied by vomiting ,9,15. MoJidabokuippo, Keishibukuryogan, Tokishakuyakusa, Maobushisaishinto, and Yokukansan were the most frequently prescribed Kampo medicines for whiplash-associated disorder. Jidabokuippo and Keishibukuryogan have been prescribed for the management of sprains and trauma or bruises ,8,9,14.Nijutsuto and Keishikajutsubuto were the most frequently prescribed Kampo medicines for frozen shoulder. Nijutsuto has been the first-line Kampo medicine for the treatment of frozen shoulder ,9. KeishThe interesting thing about the present survey is that we usually prescribed Yokukansan, Kamishoyosan, and Kososan, which have generally been prescribed for the management of psychological symptoms ,13,16,17Since pain is an interactive psychophysiological behavioral pattern, it is important for medical staffs to recognize the biopsychosocial model when understanding and caring for patients with chronic pain. Thus, an interdisciplinary approach is often recommended and considered to be extremely relevant in providing appropriate therapeutic care for patients with chronic and intractable pain . That isThere are merits and demerits for the clinical application of Kampo medicine, when compared with Western medicine. A lot of patients value Kampo medicine as a holistic, body harmonizing treatment and as a stimulant for self-healing without severe side effects . In contThere are several limitations of the study. The present report is a retrospective and nonrandomized control analysis of Kampo treatment and thus lacks the reproducibility. Since we have to clarify the specific kind of pain for personalized approach and detailed points for multidisciplinary integration, we need prospective and comparative study that might be more appropriate to support predictive, preventive, personalized value, and the reproducibility of Kampo treatment, thereby obtaining solid evidence of Kampo medicine in personalized pain management algorithm.The retrospective analysis on 221 out of 487 patients suffering from chronic pain who visited the pain center of Aichi Medical University Hospital showed that the most frequent medical complaints for which Kampo medicines were prescribed were lower back/lower limb pain, neck/upper limb pain, various facial pains, headache/migraine, whiplash-associated disorder, and frozen shoulder. Two thirds of the chronic pain patients with the use of Kampo medicines combined with Western medicine experienced further pain improvements. Moreover, we usually used several Kampo medicines generally prescribed for the management of psychological symptoms.The authors declare that they have no competing interests.Y-CPA conceived of the study, participated in its study, and conducted all experiments. All authors conducted the acquisition of data. All authors helped to draft the manuscript. All authors read and approved the final manuscript.


Purpose. New interspinous process decompression devices (IPDs) provide an alternative to conservative treatment and decompressive surgery for patients with neurogenic intermittent claudication (NIC) due to degenerative lumbar spinal stenosis (DLSS). HeliFix is a minimally invasive IPD that can be implanted percutaneously. This is a preliminary evaluation of safety and effectiveness of this IPD up to 12 months after implantation. Methods. After percutaneous implantation in 100 patients with NIC due to DLSS, data on symptoms, quality of life, pain, and use of pain medication were obtained for up to 12 months. Results. Early symptoms and physical function improvements were maintained for up to 12 months. Leg, buttock/groin, and back pain were eased throughout, and the use and strength of related pain medication were reduced. Devices were removed from 2% of patients due to lack of effectiveness. Conclusions. Overall, in a period of up to 12-month follow-up, the safety and effectiveness of the HeliFix offered a minimally invasive option for the relief of NIC complaints in a high proportion of patients. Further studies are undertaken in order to provide insight on outcomes and effectiveness compared to other decompression methods and to develop guidance on optimal patient selection. Degenerative lumbar spinal stenosis (DLSS) is the most common type of spinal stenosis, with a reported incidence of 2–8% in the general population . Due to Treatment of LSS begins with nonsurgical medical management –9. WhileInterspinous process decompression (IPD) is a minimally invasive spinal surgery in which an implant is placed between the adjacent spinal processes of the symptomatic disc level. The intraspinal process decompression system was developed for patients who have LSS with disabling neurogenic intermittent claudication and who are able to relieve their symptoms when they bend forward or flex their spine. The IPD is designed –38 to liInterspinous process decompression devices (IPDs) provide an alternative therapy to conservative treatment and are less invasive than open decompressive surgery for patients suffering from NIC. Biomechanical studies have shown that IPDs significantly reduce intradiscal pressure and facet load and prevent narrowing of the spinal canal and neural foramen .HeliFix device is an IPD that can be implanted percutaneously. It is indicated for the treatment of patients suffering from 1- or 2-level symptomatic DLSS (from L1 to L5) with NIC, exacerbated in the upright posture or by extension of the lumbar spine and relieved by flexion. The procedure has the great advantage of preserving muscular integrity, thereby respecting neuromuscular system.We present a study of 100 consecutive eligible cases, to assess safety and effectiveness of this IPD up to 12 months after procedure.HeliFix IPD was implanted at symptomatic levels in 100 patients, 42 men and 58 women, of mean age 56 years (range 32–81 years). All patients were selected on the basis of a history of DLSS , confirmed by MRI, with symptoms of NIC, including leg/buttock/groin pain, with or without back pain, relieved by flexion. If back pain was also present, it was to be partially relieved when flexed. Patients had to be able to sit for 50 min without pain and walk a distance of 20 m without pain.NIC was observed preoperatively in 84 patients, low back pain in 62, and leg pain in 47.Mean VAS was 8, and mean Roland Morris score was 18.Disability, which is defined after standing laterolateral X-rays, was present in 74 patients as angular instability (ROM > 10°) and/or 1st degree (<4 mm) sagittal degenerative spondylolisthesis. Data are summed in All patients have been treated in the prone position : 3% under general anesthesia and 97% receiving a local anesthetic and mild sedation. After radiographic identification of the surgical level, a 1.5 cm incision is made at the affected level, 6–10 cm lateral to the midline.The IPD is inserted in the interspinous space after preparing the space by opening the interspinous ligament and after determining the shape of the device. These two targets are reached by using a series of proof elements which are collocated on the tip of trocars.Under fluoroscopy, the first sharp, 5 mm thick, trocar is introduced and advanced through the interspinous space. After its removal another trocar bringing on the tip a proof element of 8 mm size is introduced. The percutaneous insertion of increasing size proof elements of 10, 12, 14, and 16 mm allows a gradual distraction of the interspinous area to measure the optimal decompression and prevent overdistraction .The size of the needed IPD is determined by monitoring under lateral fluoroscopic X-rays the dilation of the disc height, comparing it with the disc height observed at the beginning of the procedure. Simultaneously the other criterion for determining the size of the needed IPD is the resistance which is met in screwing the sharp proof elements in the interspinous pace. A rather hard resistance needs to be met, as well as the sensation of bone grasping.Once the size is determined, the definitive HeliFix device is secured on the trocar and introduced. The IPD device follows an innovative concept that features an implant with a self-distracting helical tip which is “screwed” in the interspinous space, working with the intact supraspinous ligaments to keep it in place.Changes in physical examination data, visual analogue scale (VAS) pain assessments , walking condition and distance, use of pain medication, and adverse events (AEs) were also assessed. Immediate postprocedure radiographs were compared with follow-up radiographs by an independent radiologist in order to demonstrate the position of the implant .Patients were visited monthly in the first three months, and again at 6 and at 12, by a specialized observer (Raul Saggini).P < 0.005). The statistically significant improvement from baseline was maintained up to 12 months (P < 0.005). Statistical analysis was performed with Fisher test, by using The SISA Binomial software [Baseline data of patients: 90 patients were treated at 1 level and 10 patients (10%) at 2 levels; no patient was treated at 3 levels, even if it was evident that, at entry to the study, 12 patients had several levels of lumbar spinal stenosis. The choice was dictated by the clinical observation data. No particular problems were encountered at L4-L5 level in patients with a prominent iliac crest, and an oblique entry was sufficient to ease implantation. Six weeks after procedure, the mean percentage change in score evaluations indicated a statistically significant improvement from baseline (software .(a) Mean VAS improved from 8 to 4, and mean Roland Morris score improved from 16 to 9.(b) Low back pain, previously present in 62, was abolished in 25, improved in 35, and remained unchanged in 2.(c) Leg pain, previously present in 47, was abolished in 18, improved in 25, and remained unchanged in 4. The mean score for leg pain decreased from 6 ± 1 at screening to 2 at 7 days, while the mean score for buttock/groin pain decreased from 7 ± 1 at screening to 3 at 7 days. A gradual improvement in back pain was observed: the mean score decreased from 8 ± 1 at screening to 4 ± 1 at 7 days and 3 ± 1 at 6 weeks and maintained thereafter up to 12 months.12 months after procedure.(d) NIC, previously present in 84, was abolished in 29, improved in 47, and remained unchanged in 8. Twelve months after procedure, 76% of patients with IPDs implanted were judged by their physician to walk “fluently.” An improvement in walking distance was also observed up to(e) Patient satisfaction index (PSI), assessed using the PSQ-18 questionnaire, is as follows: quite satisfied 26 patients, satisfied 66, and nonsatisfied 8. During time PSI did not significantly change.P < 0.005) from baseline at all time-points. Immediate improvements were seen in leg and buttock/groin pain after procedure and were maintained up to 12 months.(f) VAS pain scores for leg, buttock/groin, and back showed that pain decreased significantly ((g) Medication intake up to 12 months: while pain scores decreased over time, the use of pain medication (including strong pain medication such as opioids) decreased. The number of patients requiring 3 times daily dosing rose 5 days after procedure but subsequently immediately fell. Twelve months after procedure, the percentage of patients requiring pain medication (codeine and paracetamol) was significantly reduced. A high proportion of patients did not require any medication at all (72% of patients versus 25% at baseline).Data showed a significant improvement from baseline up to 12 months after procedure.(h) Number of treated levels had no significant impact on changes in pain or Roland Morris scores. Only in the first postop week, the back pain can be considered to be more relevant in double level treatments.(i) Safety: no serious adverse device effects (SADEs) were reported during this study.Three minor adverse effects were reported: the first was a marked back pain in one patient due to a huge paravertebral muscles hematoma one day after the procedure; the second and the third were a mild back pain in 2 patients between 2 and 7 days after the procedure.(j) Device position and removal: final position of IPD in the interspinous space was assessed by X-ray in anteroposterior and laterolateral views, confirming the correct position of IPD throughout the study, with no cases of implant dislocation observed. During the 12-month postprocedure period, 2 patients had their IPD removed after 3 months, due to persistent or recurring symptoms. One device was in L3-L4 and a second in L4-L5. No spinous process fracture or device malpositioning was observed.Safety and effectiveness of IPD were evaluated for 12 months in DLSS patients with NIC. IPD effectively and quickly alleviated symptoms of spinal stenosis as demonstrated by changes in symptoms severity and physical function scores, VAS pain scores, the use of pain medication, and improvement in walking distance .Data demonstrate that IPD can be beneficial for up to 12 months after implantation in a high proportion of patients, with the majority of patients showing clinically important improvements versus baseline.Following surgery, an immediate improvement was observed in leg and buttock/groin pain; however, back pain showed a more gradual improvement, which may suggest that patients with classical claudication and leg symptoms as their predominant complaints are the optimal target population for this IPD.We did not observe a significant long-term effect on the degree of lordosis in our clinical series.In the literature the most commonly reported SADEs up to 12 months after procedure are back pain, spinal claudication, and spinous process fracture. Spinous process fracture, not observed here, may be considered as potentially risk related specifically to interspinous process decompression, both in terms of the procedure and the device itself –44. FracDuring the 12 months after procedure, 2 patients had the IPD removed. In both cases a microdiscectomy was performed, since foraminal stenosis by intraforaminal disc protrusion was persistent and it was considered to be the real cause of nerve dysfunction. The incidence of device removal during this time was low –48. In aAnalysis on potential predictors for a successful outcome at 12 months in the present study did not reveal new insights to aid patient selection in the future, possibly because the number of patients not benefiting from the procedure was relatively low, and the range of baseline characteristics was wide. More research is needed to define the optimal patient population for this type of procedure. However, the minimally invasive IPD is a viable alternative for selected patients, is quick and simple to implant, and leaves options open for further treatments in the future.It is known that muscular function is essential for dynamic activity and stability of the spine and that the system is regulated by passive, active, muscular, and neural subsystems. The neural subsystem receives information from the various transducers, determines specific requirements for spinal stability, and causes the active subsystem to achieve the stability goal. Individual muscle tension is measured and adjusted until the required stability is achieved. The requirements for the spinal stability and, therefore, the individual muscle tensions are dependent on dynamic posture and external loads . It is tOur data indicate that in a period of up to 12-month follow-up, thanks to safety and effectiveness of the HeliFix procedure and device, a minimally invasive option is offered for the relief of NIC complaints in patients with symptomatic DLSS with NIC.


Migraine is a disabling neurological condition characterized by headache attacks, hypersensitivities to visual, auditory, olfactory and somatosensory stimuli, nausea and vomiting. Peripheral and central sensitization of trigeminovascular neurons seem to play a critical role in different aspects of migraine pathophysiology. In the To investigate perception intensity of trigeminal heat stimulation (THS) in patieWe enrolled 80 patients with migraine (40 patients with MwoA CA- and 40 patients with MwoA CA+) and 60 HC. THS was performed using the contact heat evoked potential stimulator (CHEPS) at three different intensities: a low-innocuous stimulus at 41°C and two painful heat stimuli at 51° and 53°C (to provide a moderate-noxious and a high-noxious stimulus). Subjects had to verbally rate the intensity perception of the experimental stimulus by means of a numerical rating scale (NRS) ranging from 0 (“no pain”) to 10 (“worst pain imaginable”).NRS of pain perception was not significantly different between patients with MwoA (as a group) and HC at any level of experimental stimuli. The absence of significant differences in pain perception was also found between patient groups defined as patients with MwoA CA- and with MwoA CA+ compared to HC, at any level of experimental stimuli.In the present study, by using three predefined temperatures, we demonstrated that pain intensity ratings are not significantly different between both CA+ and CA- migraine patients and patients with migraine as a group compared to HC. Previous studies suggested a low heat pain threshold in migraine patients during interictal period. HoweverWritten informed consent to publication was obtained from the patient(s).