This study aims to explore the changes in pain intensity and quality of life (QoL) experienced by patients with painful diabetic neuropathy (PDN) treated with spinal cord stimulation (SCS) and conventional medical practice (CMP).Patient-reported pain intensity and QoL data were obtained from participants in an international multicentre randomised controlled trial comparing SCS versus CMP. Data were collected at randomisation and 6 month follow up by means of a visual analogue scale for pain intensity, the EuroQoL Visual Analogue Scale (EQ VAS) and the EuroQol EQ-5D index. Quality-adjusted life years (QALYs) were calculated for each treatment using the ‘area under the curve’ method. Differences in QALYs were calculated after adjusting for between-treatment imbalances in baseline QoL.At 6 months, patients allocated to SCS reported larger reductions in pain intensity and improvements in QoL measured by the EQ-5D utility score and EQ VAS as compared to those allocated to CMP. Initial calculations of QALYs for the SCS and CMP groups suggested no statistical differences between the groups. Adjusting for imbalances in baseline EQ-5D scores showed SCS to be associated with significantly higher QALYs compared to CMP.SCS resulted in significant improvement in pain intensity and QoL in patients with PDN, offering further support for SCS as an effective treatment for patients suffering from PDN. From a methodological point of view, different results would have been obtained if QALY calculations were not adjusted for baseline EQ-5D scores, highlighting the need to account for imbalances in baseline QoL. Diabetes mellitus is a common chronic condition with an increasing prevalence estimated to reach 4.4 % of the world population in 2030, the equivalent of 366 million people . As a reA number of oral pharmacologic treatment options are available for the management of PDN, including serotonin-norepinephrine reuptake inhibitors (SNRIs), tricyclic antidepressants, carbamazepine, venlafaxine, duloxetine, and amitriptyline. These may be effective for short-term management of PDN . HoweverSpinal cord stimulation (SCS) is a widely-used intervention for the management of neuropathic pain conditions, and it has been suggested as a promising treatment option for PDN. Randomised controlled trials (RCTs) have demonstrated the effectiveness of SCS in the management of failed back surgery  and compWe hypothesise that patients with PDN treated with SCS obtain larger reductions in pain intensity and improvements in QoL when compared to those patients with PDN treated with CMP alone. The aim of this study was to explore the changes in pain intensity and QoL experienced by patients with PDN treated with SCS and CMP. To this end, we analysed patient responses to three instruments , EQ VAS, EQ-5D index) obtained from a multicentre randomised controlled trial.n = 20) or conventional medical practice supplemented by SCS . Patients randomised to the SCS group underwent a screening trial lasting up to 7 days to assess their response to SCS, and a pulse generator was only implanted if the screening trial was successful. 6 months post randomisation, patients in the CMP group could cross over to SCS therapy if adequate improvement had not been achieved.The design and results of the RCT have been described previously in detail . In brieInformation on patients’ age, gender, type and duration of diabetes, pain intensity and onset of pain was collected prior to randomisation (baseline). Pain intensity was assessed using a 100 mm visual analogue scale ranging from 0 (no pain) to 100 (worst possible pain) . The VASt tests. Changes in these scores between different time points (baseline and 6 month follow up) were assessed using paired-samples t tests. Changes in levels of EQ-5D dimensions were evaluated through the Mann–Whitney test for between-group analyses, and the Wilcoxon signed-rank test for within-group analyses. Baseline EQ-5D scores are a strong predictor of total QALY scores, therefore mean differences in QALYs were calculated after adjusting for imbalances in baseline scores between groups [Comparisons of scores obtained from self-reported measures  between groups were carried out using independent-samples n groups . Mean diBaseline characteristics of the study sample are reported in Table In the SCS group, minimal clinically important reductions in pain intensity (10–30 %) were reported by four (11 %) of the patients, moderate important reductions (30–50 %) were experienced by three (8 %) while substantial clinical differences (≥50 %) were reported by 24 (67 %) of the patients. Of the patients randomised to CMP, six (33 %) reported minimal clinically important reduction in pain intensity and only one (6 %) patient reported ≥50 % pain relief.No statistically significant differences were observed for the CMP group between baseline and 6-month follow-up for the VASPI, EQ-5D utility or EQ VAS scores Table . StatistM = 0.23, SD = 0.11) and CMP  groups based on QALYs calculated as the area under the curve did not show statistically significant differences between treatments . As baseline QoL is a strong predictor of total QALY scores, we calculated differences in QALYs between groups by adjusting for baseline imbalances in EQ-5D scores . Patients randomised to SCS experienced a higher QALY gain when compared to the patients receiving CMP.Comparison of the SCS  crossed-over to SCS following the 6-month follow-up. Of the 36 patients that were implanted with an SCS, 34 (94 %) continued to receive SCS therapy after the 6-month study endpoint.This study analysed data obtained from an international multicentre RCT to compare the levels of quality of life reported by patients treated with SCS and CMP. Results showed that SCS leads to statistical and clinical significant improvement in pain intensity and quality of life in patients with PDN as compared to CMP.Pain intensity findings are consistent with previous non-randomised studies of SCS in patients with PDN –23. ThesThe results of this study are based on a 6-month follow-up. This was the primary endpoint of the de Vos et al. RCT . The effPainful diabetic neuropathy may interfere substantially with quality of life aspects . InterprAn initial evaluation of the QALYs based on calculation of the area under the curve suggested that there were no statistically significant differences between the groups. However, it has been argued that such results may be biased due to imbalances in baseline utility scores . FurtherThe subjects of this study were derived from the de Vos et al.  trial whIn conclusion, the pain experienced by the patients recruited for this study had a negative impact on their quality of life. When analysing QALYs based on the area under the curve, it is important to take into consideration possible baseline imbalances in EQ-5D utility scores. Disregarding baseline imbalances could potentially lead to erroneous and misleading conclusions. Spinal cord stimulation resulted in clinical and statistical improvements in pain and quality of life of patients with painful diabetic neuropathy. The results of this study further support spinal cord stimulation as an effective alternative for those patients with refractory painful diabetic neuropathy in the lower extremities.


Patients suffering from migraine or tension-type headache (TTH) often treat their complaints with over-the-counter (OTC) medications. Fixed dose combinations of acetylsalicylic acid, paracetamol and caffeine (APC) are among the most commonly used analgesics, and their efficacy for treating acute headache pain has been well demonstrated. This investigation was run to better characterize patients who treat their headache with OTC APC combinations, as well as treatment effects.®) were handed a questionnaire, which had to be filled out at patients own discretion after taking the medication. Demographics, pain characteristics and perceived efficacy and tolerability data were analysed with descriptive statistics.A pharmacy-based patient survey in 164 German pharmacies was performed. Patients (age ≥18 years) who purchased APC analgesics , with 828 patients for TTH and 206 for migraine. About one third of patients in the subgroup migraine did not report their pain as migraine. Nausea, photophobia/phonophobia turned out to be the most distinguishing feature between migraine and TTH. The main reasons for purchasing the product were recommendation by the pharmacists (40.5 %) and/or friends or relatives (24.4 %). 74 % of TTH and 55 % of migraine patients reported onset of pain relief within the first 30 min. More than 90 % rated efficacy as well as tolerability to be “good” or “very good”.The main reason for purchasing APC products in the pharmacy are TTH or migraine. About a third of patients fulfilling the IHCD-II criteria for migraine failed to recognize their headache as migraine. This could be explained e.g. by patients’ misconceptions about their pain. Patients’ assessments of efficacy and tolerability showed that the investigated APC combinations are valuable for the treatment of TTH and migraine headache. These data complement those of randomized clinical studies on such preparations. Fixed dose combinations of acetylsalicylic acid, paracetamol and caffeine are in widespread use for the treatment of episodic headaches. Typical over-the-counter (OTC) products contain 250 mg acetylsalicylic acid, 200 or 250 mg paracetamol and 50 mg caffeine per tablet (APC combination), with the recommended dose of one to two tablets every 4–8 h up to six tablets daily.APC combinations are among the best investigated analgesics for the treatment of acute headaches in self-medication. In all controlled, randomized, placebo-controlled studies performed so far, this triple combination showed statistically significant and clinically relevant superiority over comparators, among them the mono-compounds acetylsalicylic acid, paracetamol, and ibuprofen, when used with the maximum recommended OTC dose, as well as the prescription-only migraine medication sumatriptan  or 250 mg paracetamol (“INTENSIV”) and 50 mg caffeine per tablet] and consented to participate were handed a questionnaire, which had to be filled out at patients own discretion after taking the medication, preferably on the same day. Patients were asked to send the completed questionnaire to the institute that analysed the data  in a sealed envelope. Personal data enabling to identify a patient were not collected. Thus no formal ethical approval was necessary.This prospective, non-interventional survey was run in 164 German pharmacies between October 2013 and March 2014. Patients who purchased ThomapyrinPreconditions for participation comprised age ≥18 years, purchase of one of the both APC medications for treatment of headache or any other pain, willingness and ability to independent, plausible and timely completion of the questionnaire. No exclusion criteria were defined.The paper based questionnaire obtained—among others—information on sex, age, height, weight, frequency of pain within last 30 days, limitation of daily activity by pain (within the last 30 days), and reasons for purchasing this products.® to others.Parameters related to last pain episode provoking the intake of the drug: first usage (yes/no), type of pain , intensity of pain , time of pain event, time of first usage of the drug after onset of pain event; if applicable: time of repeated usage, time to onset of pain relief, subject’s assessment of efficacy, subject’s assessment of tolerability, willingness to recommend usage of ThomapyrinThe characterization of a subject’s type of headache pain was based on the diagnostic criteria of the International Classification of Headache Disorders , i.e. pain location ; pain characteristics ; whether pain increased due to physical strain ; occurrence of the accompanying symptoms nausea, photophobia or phonophobia . A subject was assigned to subgroup “migraine” if (1a AND 2a AND 4a) or (1a AND 3a AND 4a) or (2a AND 3a AND 4a) were met. A subject was assigned to subgroup “TTH” if [1b AND 2b AND (3b OR 4b)] or (2b AND 3b AND 4b) or (1b AND 3b AND 4b) were met. Moreover, patients were asked to assign their headache to “migraine” or “headache” . A subject was assigned to the subgroup “other”, if the subject’s diagnosis of “type of pain” was “other”. In case a subject could not be assigned unambiguously to any subgroup, the subject was omitted from the analyses pertaining to this subgroup.Any adverse drug reaction arising out of completed questionnaires had to be reported by the institute that collected and analysed the data to Boehringer Ingelheim and was processed accordingly.Data management and statistical analysis were performed using SAS, Version 9.2. As appropriate for the design of the study, only descriptive analyses and statistical modelling were performed. Numerical data were compared exploratively between subgroups using a Wilcoxon or Kruskal–Wallis test. Analyses were done for the total study population and for study subgroups separately.A total of 1302 patients completed the questionnaire. The data from four patients were excluded from the analysis, because three of them had no documented intake of the product, and one did not report the type of pain treated. Thus, the data of 1298 patients were available for the analysis. A summary of the main demographic variables is provided in Table A total of 1284 patients reported a mean of 5.4 ± 5.5 days with any kind of pain during the last 30 days. Female patients reported overall more days with pain than males . Migraine patients reported more days with pain than TTH patients .Information on the number of days  where activities of daily living could not be performed due to pain was obtained from 1057 patients. In total, a mean of 1.5 ± 3.2 days was reported. Females reported slightly more days than male patients , and migraine patients more than TTH patients .Mean baseline pain intensity before the intake of the medication was 5.9 ± 1.7. Migraine patients reported more severe pain  than TTH patients ; no difference in baseline pain between male and female patients was found.Based on requested information about the last episode of headache, 828 patients fulfilled the IHCD-II criteria for TTH. 760 patients (91.8 %) of them documented non-migraine headache themselves, while 12 patients (1.4 %) documented migraine. The remaining 56 patients (6.8 %) did not clearly allocate their headache pain to one specific type.A total of 206 patients were attributed to migraine. 111 patients (53.9 %) of them diagnosed migraine themselves, while 61 patients (29.6 %) documented non-migraine headache. The remaining 34 patients (16.5 %) did not clearly allocate their headache pain to one specific type. Thus, about one third of the patients fulfilling the IHCD-II criteria for migraine did not recognize their pain as migraine.Thirty patients among all reported to suffer from migraine and non-migraine headache. The acute episode of nine of them (30.0 %) was assigned to TTH, 21 of them (70.0 %) to migraine.The pain characteristics are shown in Table The reasons for buying the medication are shown in Table The median time between occurrence of the pain episode and intake of the medication was 45 min (n = 942), with no difference between male and female patients. However, migraine patients took the medication earlier than those suffering from TTH . Patients who took the APC combination for the first time waited longer than those who already knew the product .The mean dose at first intake was 1.4 ± 0.5 tablets, with a mean total of 1.8 ± 1.2 tablets for the entire pain event. The mean dose was slightly higher for migraine versus TTH patients . Higher percentages of migraine patients took more than one dose during the pain episode . Consequently, the mean total number of tablets per pain episode was also higher for migraine patients .Fast onset of action of an analgesic is desired by patients and contributes to the overall impression of efficacy , these reports were addressed as off-label use. Poor efficacy was reported by the remaining 5 %. In summary, no new safety information was retrieved from the survey.No serious adverse drug reactions were reported during this survey. 95 % of the 143 adverse event reports stated intake of ThomapyrinPharmacy-based patient surveys are valuable tools to gain information on patient demographic and characteristics of the treated complaints, as well as on the effects of investigated treatments as assessed by the patient. Especially in the context of OTC treatment, such surveys can provide insights which are otherwise hard to obtain and complement those of controlled clinical trials . In addition, patients were asked to describe their headache characteristics according to ICHD-II in order to discriminate between TTH and migraine, and their personal assessment was compared to diagnoses according to ICHD-II  could be biased by patients’ expectations, as well as previous experience with the investigated medicinal products. In this survey, about 29 % of patients had no previous experience with the test products. A lower proportion of these patients reported pain relief within the first 15 min, but no relevant differences were observed after 30 min  is a valuable measure of the individual treatment success of a given analgesic. Data from investigations on OTC doses of ibuprofen and acetylsalicylic acid for the treatment of migraine attacks with comparable methodology like this study have been reported. Here, 75.6 % of patients using ibuprofen to treat their migraine, and 76.8 % of patients using acetylsalicylic acid assessed the efficacy to be “good” or better Goebel  comparedIn two controlled clinical trials on treatment of acute migraine, 38.2 and 58.6 % patients taking ibuprofen reported “good” efficacy  APC combination offers clinical benefit to a higher number of patients. This conclusion is also supported by meta-analyses on caffeine as co-analgesic (Derry et al. The main reason for purchasing APC products in the pharmacy are TTH or migraine. About a third of patients fulfilling the IHCD-II criteria for migraine failed to recognize their headache as migraine. This could be due to patients’ misconceptions about their pain, or the extensive symptom overlap between migraine and TTH. Education of patients about their headache disorder might be a way to improve treatment of migraine and TTH in future. Patients’ assessments of efficacy and tolerability of the investigated APC combinations showed that the investigated APC combinations are beneficial for the treatment of TTH and migraine headache. These data complement those of randomized clinical studies on such preparations.Taken together this study shows that pharmacy-based surveys can provide valuable data on patients and their ailments. Moreover, they can broaden our knowledge on treatment of these with OTC medicinal products, and provide information on the individual patient experiences with the investigated medication.


N-methyl-D-aspartate receptor antagonists are potential therapies for neuropathic pain, and memantine has a good tolerance profile. A preclinical study recently reported that presurgery memantine may prevent neuropathic pain development and cognition dysfunction. Considering the high prevalence of breast cancer and of post-mastectomy neuropathic pain, a clinical trial is carried out to evaluate if memantine may prevent neuropathic pain development and maintain cognitive function and quality of life in cancer patients.A randomized clinical trial (NCT01536314) includes 40 women with breast cancer undergoing mastectomy at the Oncology Hospital, Clermont-Ferrand, France. Memantine  or placebo (n = 20) is administered for 4 weeks starting 2 weeks before surgery. Intensity of pain, cognitive function, quality of life and of sleep, anxiety and depression are evaluated with questionnaires. The primary endpoint is pain intensity on a 0 to 10) numerical scale at 3 months post-mastectomy. Data analysis is performed using mixed models and the tests are two-sided, with a type I error set at α = 0.05.The hypothesis of this translational approach is to confirm in patients the beneficial prophylactic effect of memantine observed in animals. Such a protective action of memantine against neuropathic pain and cognitive dysfunction would greatly improve the quality of life of cancer patients.NCT01536314 on 16 February 2012ClinicalTrials.gov:  Medical treatment of neuropathic pain (NP) is still far from being satisfactory, with less than half the patients achieving significant benefit with any pharmacological drug . Several−15) of pain intensity, cognition, quality of life and quality of sleep questionnaires, participants are randomized into two parallel groups: memantine (n = 20) or placebo (n = 20). Memantine or placebo (lactose) is given orally for 4 weeks starting 2 weeks before surgery. Memantine is given in increasing doses: 5 mg/day for 3 days; 10 mg/day for 3 days; 15 mg/day for 3 days and 20 mg/day for 5 days. Endpoints are reassessed 15 days (D0+15), 3 months (D0 + 3 months) and 6 months (D0 + 6 months) post-mastectomy. In order to maintain a good compliance and to verify that women do not develop adverse events, patients are called once a week by phone. A booklet for monitoring is completed daily by the patient for 6 months from the day of surgery. Detailed information on the present study is summarized in Figure We are conducting a randomized, placebo-controlled clinical trial in the Oncology Hospital, Clermont-Ferrand, France, in 40 women undergoing total mastectomy for breast cancer. The study has been approved in December 2011 by the regional Ethics committee  and registered on 16 February 2012 at “http://www.clinicaltrials.gov” (NCT01536314). Women provide written informed consent prior to their participation in the study during their anesthesiology visit. After baseline assessments (day (D)Women are eligible for this study if they are at least 18 years old, with a diagnosis of breast cancer, programmed for mastectomy with or without axillary dissection, able to understand and willing to follow the study protocol.Exclusion criteria comprise contraindications for memantine and hypertension, severe cardiac insufficiency or diabetes (Type I and II), alcohol addiction and treatment with specific drugs . Childbearing age, no use of effective contraceptive method, pregnancy or lactation, involvement in another clinical trial and inability to comply with the requirements of protocol are other exclusion criteria.The primary objective of this study is to evaluate if memantine administered before and after mastectomy may prevent pain development at 3 months post-mastectomy when compared to the placebo group. The endpoint at 3 months was chosen because chronic pain is usually defined as pain lasting longer than 2 to 3 months , 18, andThe secondary objectives are to estimate at 3 and 6 months post-mastectomy the pain intensity, the analgesic concomitant medications, the impact of treatment (memantine/placebo) on cognitive function, quality of life, sleep, anxiety and depression, the impact of cancer chemotherapy-induced pain and cognitive impairment and the prevalence of phantom breast experience.The primary endpoint is the pain intensity evaluation by numerical scale in memantine and placebo groups at 3 months post-mastectomy. The scale ranges from 0 (no pain) to 10 .Secondary endpoints are the evaluation of pain at the screening visit, at 2 weeks, 3 months and 6 months after mastectomy , neuropathic pain , cognition , sleep (Leeds sleep questionnaire), quality of life (Short-Form-36), and anxiety and depression . The summary of the different evaluations for a patient is reported in Table This self-administered questionnaire provides information on the intensity of pain, along with the degree to which the pain interferes with the everyday functioning of life including: mood, walking, general activity, relations with others, sleep, enjoyment of life .This questionnaire allows the patient to describe pain experienced during the last 48 hours . It has Neuropathic pain in four questions is a clinical tool for the diagnosis of neuropathic pain . This quNeuropathic Pain Symptom Inventory is a self-questionnaire and includes 10 pain descriptors . IntensiThis non-verbal cognitive test assesses the ability of speed, executive functions, attention, concentration, and visual perceptual speed , 24. TheThe digit symbol substitution test is a neuropsychological, non-verbal test, which assesses cognitive deficit and brain damage associated with aging and/or depression . It alsoThe Short-Form-36 is a questionnaire evaluating the quality of life of patients , 27. It The Leeds sleep evaluation , 29 quesThe Hospital Anxiety and Depression scale is a self-administered questionnaire in 14 items completed by the patient . It is uWomen with breast cancer are informed by their anesthetist 2 to 3 weeks before mastectomy. On the day of the visit, inclusion and exclusion criteria are verified and written informed consent is obtained by the physician. After clinical examination and pain evaluation, the patient fills in the questionnaires. A clinical nurse independent from the protocol obtains the randomization number from the hospital pharmacy and the patient is then randomized in the memantine or placebo group. Treatment allocation follows a predetermined randomization list and is generated using random blocks. Memantine and placebo treatments are packed in similar blisters covered with an identical label indicating batch number, expiry date and sponsor code with no indication of the name of the drug. The nurse gives the treatment to the patient in an independent room after questionnaires have been filled. In order to maintain blinding, the consent physician  cannot guess allocation at any time and does not see the patient again before they leave hospital.The number of subjects required is 40 chronic pain patients (20 in each group). The minimum δ difference in numerical scale pain between memantine and placebo groups at 3 months is estimated at 1.6 and σ standard deviation at 1.5, estimated from published data of the literature , 32, witStatistical analyses will be performed with Stata software . Concerning the primary objective, comparison between the randomized groups will be performed using an analysis of covariance with baseline score as a covariate . The corNP is difficult to treat and NMDAR antagonists, such as ketamine, dextromethorphan or memantine , 6, 35, This trial of prophylactic memantine given long before surgery in cancer patients aims to evaluate if memantine may diminish overall post-surgery pain and prevent NP development. It aims also to evaluate the concomitant impact on cognition and quality of life. We showed in animals that pre-surgery memantine prevents cognition impairment . Breast Given that mastectomy with or without chemotherapy can induce NP and cognitive and emotional impairment, these complications represent a real burden for women with breast cancer, and global care is a priority to improve their well-being. If our study confirms preclinical results, memantine given before mastectomy could be a new prophylactic strategy to counteract NP development. It would provide a preventive therapeutic innovation to decrease the incidence of post-operative and chemotherapy-induced NP, cognitive impairment and quality of life impairment and comorbidities that generally accompany breast cancer pathology.Recruitment started in March 2012.


Aim. The objective of the current study was to evaluate the reduction of edema and pain with the use of elastic stockings. Method. The effect of walking on a treadmill for 50 minutes in the evening wearing elastic compression stockings on pain and edema was evaluated in a prospective randomized crossover clinical trial. In Assessment 1, the legs of participants were measured by volumetry at 7:00 a.m. and they were asked to perform their normal daily activities and to return at 4:00 p.m. Forty-two legs of 21 female patients with ages of the participants ranged from 32 to 72 years with signs and symptoms of chronic venous disease. The sizes of the legs of all patients were evaluated by water displacement volumetry and a visual analog scale was used to assess pain. Results. After walking for 50 minutes on the treadmill, the volume reduced . In relation to pain, there was a reduction in pain after the treadmill session using the elastic stocking . Conclusion. The reduction of edema and pain of the legs during the course of the day can be accomplished with the use of elastic stockings, as well as walking. Chronic venous disease affects millions of people throughout the world causing signs and symptoms that lead to disablement from work and loss of quality of life , 2. HoweAnother condition that may cause or aggravate the symptoms is the external environment due to gravitational pressure and temperature. It has been reported that individuals working in specific positions may feel leg pain, have a bloated feeling, have a feeling of heaviness, and have several other disturbing sensations . These sElastic stockings must be correctly indicated and adjusted to the leg. Artifacts such as folds and pleats can exert a strangling effect. Compression stockings act by exerting a pressure at the stocking-skin interface that is transmitted to the surrounding tissues causing a pressure differential in the cell interstice and arteries, veins, and lymphatics. While, at rest, stockings generate an almost constant pressure called resting pressure, with movement, such as walking, the stockings generate variations in pressure .The use of elastic stockings is well-defined for the treatment of venous and lymphatic disease; however, a careful analysis is required of the benefits of adherence to treatment and unpleasant situations such as feeling hot, irritation, and itching. In tropical countries, such as Brazil, the heat is a limiting factor which can lead to treatment failure in a short period of time . HoweverOne study evaluating the use of stockings during half the day showed that this benefits compliance; even so compression mechanisms should ideally be used during the entire day . AnotherThe effect of walking on a treadmill for 50 minutes in the evening wearing elastic compression stockings on pain and edema was evaluated in a prospective randomized crossover clinical trial.Forty-two legs of 21 female patients were evaluated in this study conducted at the Clinica Godoy in 2013/2014. The ages of the participants ranged from 32 to 72 years with a mean of 49.5 years.Patients with signs and symptoms of chronic venous disease with at least one leg having a Clinical, Etiology, Anatomy and Pathophysiology (CEAP) classification of C3 (swollen ankle (oedema) due to varicose veins or hidden varicose veins-venous reflux) were enrolled in this study. The inclusion criteria were edema and fatigue of the legs which worsened during the day but improved with the rest and with elevation of the legs and pain in the legs. The exclusion criteria were varicose veins with CEAP classifications 4, 5, and 6, difficulty walking, morbid obesity, orthopedic changes, and other diseases clinically evaluated which might cause the symptoms of the legs.The sizes of the legs of all patients were evaluated by water displacement volumetry and a visual analog scale was used to assess pain.In Assessment 1, the legs of participants were measured by volumetry at 7:00 a.m. and they were asked to perform their normal daily activities and to return at 4:00 p.m. At 4:00 p.m., the legs were again evaluated by volumetry and patients indicated the pain that they felt using the analog pain scale. After putting on Venosan 20/30 mmHg knee-length elastic compression stockings, participants walked for 50 minutes on a treadmill at a speed of 3 km per hour. They were again assessed by volumetry and using the analog pain scale.In Assessment 2, the legs of the participants were again measured by volumetry at 7:00 a.m. and the stockings were worn during the entire day with a further evaluation at 4:00 p.m. .Consecutive patients were randomly assigned to two different groups where on the first day of the study one group followed Assessment 1  and the t-test and the Wilcoxon signed rank test were used for statistical analysis with an alpha error of 5% being considered acceptable.The paired The study was approved by the Research Ethics Committee of the Medicine School in Sao Jose do Rio Preto (FAMERP). The patients were provided with details of the study and those who chose to participate signed informed consent forms.Thirty-six of the legs were classified as CEAP C3 and six were CEAP C2.t-test: p value < 0.0001). After walking for 50 minutes on the treadmill, the volume reduced to 3070.92 mL .On the day that the elastic stockings were only used during the treadmill session Assessment 1 , the meat-test: p value < 0.0001).On the day that the elastic stockings were used during the entire day Assessment 2 , the inip value < 0.007) p value < 0.01).In relation to pain, there was a reduction in pain after the treadmill session using the elastic stocking (Wilcoxon signed rank test: The current study evaluated patients with signs and symptoms of chronic venous disease classified as CEAP C3. It demonstrates that using elastic stockings during the entire day reduces the edema and pain. The pain was one of the most important symptoms in the evaluation of these patients because it is more uncomfortable than the edema itself. In the clinical practice, the edema is not always considered important; patients often neglect it, claiming that it is normal due to their daily activities.The proposed treatment was the use of Venosan 20/30 knee-length elastic compression stockings which proved to be effective in reducing or controlling the edema and pain. However, stockings with higher compression ratings are recommended in more advanced cases of chronic venous disease.The evaluation of the edema and pain showed that both these variables worsened during the day when stockings were not used but that they improved after wearing elastic stockings while walking on the treadmill. This opens a discussion about the possibility of more flexibility in the use of elastic stockings by patients. The best option is to use the stockings during the entire day; however, it has been shown that use for half the day is useful to reduce edema .This new option, to use stockings in the evening when there is edema, has already been evaluated by the authors . This stThis study was carried out in Brazil, a tropical country, and during the summer when the edema and other symptoms of venous and lymphatic diseases are aggravated the most. In the summer, there is more resistance to the use of elastic stockings by patients and so this flexibility may help to relieve the symptoms. The use of medications is another therapeutic option in these cases, but not every patient is adherent to drug treatment.The reduction of edema and pain of the legs during the course of the day can be accomplished with the use of elastic stockings, as well as walking on a treadmill for 50 minutes in the afternoon while wearing elastic stockings.


Pain is a common and often debilitating consequence of cancer and its treatment. Efforts to improve pain management for patients diagnosed with cancer have not resulted in widespread patient reports of acceptable management of pain. Patients and providers alike remain opiophobic due to a number of issues, resulting in suboptimal management of pain. Recent literature has revealed that it may be possible to prevent pain related to cancer and its treatment and therefore avoid or decrease the amount of opioids used to treat pain. This may result in better quality of life for patients. Several newer antiepileptic drugs (AEDs) have been found to decrease the perception of pain in a number of patient populations, including those with head and neck cancer. The side-effect profile for the newer AEDs is mild and well tolerated. Future efforts should focus on the use of newer AEDs to prevent pain in other cancer populations, with a focus on ideal dose and scheduling. Once established, recommendations regarding the prevention of pain in patients with cancer can be incorporated into national guidelines. In 2014, it is estimated that more than 1.6 million people in the United States received new cancer diagnoses and 580,000 cancer-related deaths likely occurred . Of thesTreatment for oropharyngeal head and neck cancer has changed as therapies have improved. In the past, patients generally underwent extensive and physically deforming surgery. Many of these patients required postoperative chemotherapy and/or radiation therapy. These treatments often resulted in short- and long-term side effects that impact the quality of life (QOL) of the patient . More rePain is one of the most prevalent and feared consequences of cancer and its treatment. Regardless of changes and improvements in therapy, patients undergoing treatment for cancer do experience pain. Tumors may invade or compress blood vessels and/or nerves. Treatments are not specific to cancer cells; damage to normal cells results, causing side effects . IncreasAside from patient-related barriers and despite efforts to educate providers, insufficient progress has been made in the area of pain management. Cancer pain remains undertreated . This isA relatively recent trend in the clinical management of pain is a focus on prevention . SeveralChemotherapy and/or radiation treatment given to eradicate cancer also affect cells that are multiplying rapidly. For patients undergoing treatment for head and neck cancer, a resulting painful mucositis may occur. Attempts at preventing or minimizing this pain with AEDs may result in the use of decreased dosages of opioids.The purpose of this article is to review the physiology of pain transmission, describe studies on the use of AEDs in pain prevention, and model the application of this strategy to the care of patients with head and neck cancer.In the acute setting, pain protects the body from harm by acting as a warning. Pain occurs as a result of stimulation of a group of receptors called nociceptors. Nociceptors, which are located at nerve endings of C and Aδ fibers, are activated by thermal, mechanical, or chemical stimulation. These noxious stimuli are converted into electrical activity within the peripheral nervous system—a process referred to as transduction. As stimulation of the nociceptor occurs, sodium, potassium, and calcium rush into the area and cause depolarization of the cell. This results in transmission of the impulse along the nerve to the level of the dorsal horn. The rapidity of the transmission depends upon the type of nerve fiber affected (myelinated vs. unmyelinated). The intensity of the impulse depends upon the intensity of the stimulus generated. Activation of the nociceptors results in the release of excitatory neurotransmitters, neuropeptides, and neuromodulators into the synapses between cells.Glutamate is the major excitatory neurotransmitter in the central nervous system (CNS). Activation of the N-methyl-D-aspartate (NMDA) receptor appears to play a role in increasing CNS excitability . GlutamaAt the level of the dorsal horn, primary afferents synapse with interneurons prior to traveling to the final pathway in the spinal cord . The afferents release a number of neurotransmitters, resulting in a massive influx of calcium and sodium to a lesser degree. This influx is a trigger for a number of intracellular events that result in activation or deactivation of other receptors within the cell. In the postsynaptic area, there are calcium channels that are comprised of proteins with multiple subunits. These include α1 pore-forming subunits and the modulatory subunits α2δ, α2β, or α2γ. The α2δ subunit regulates the amount and operation of activation and inactivation of the channel. In C nociceptors, the α2δ subunit is dramatically upregulated after nerve injury and plays a key role in injury-related hypersensitivity and allodynia .Inhibitory neurotransmitters also play a large role in pain transmission. Under normal circumstances , gamma amino butyric acid (GABA) and/or glycine are continuously released to decrease the excitability of the interneuron and modulate pain transmission. Often, as a result of severe and/or chronic pain, microglia are activated and release a number of cytokines that result in response to innocuous stimuli that are resultantly perceived as painful. This is referred to as central sensitization .Activation of descending pain-suppression pathways (referred to as modulation) has the ability to decrease the likelihood that a stimulus is perceived as painful and/or reduce the perceived intensity of pain. Endogenous opioids are essential in this pathway and are released from a number of locations throughout the CNS, where they can inhibit pain signal transmission . In addiSeveral classes of medications are used to treat pain. However, the focus of this article is on relevant literature reporting on the use of some of the newer AEDs in an attempt to prevent pain. Just as we ask patients to premedicate prior to known pain-provoking activities, we may be able to use AEDs to prevent or lessen the pain they experience as a result of cancer or its treatment. This represents a change in the manner in which we approach pain in patients with cancer.Mr. D was a 47-year-old male diagnosed with locally advanced poorly differentiated squamous cell cancer of the oropharynx. The tumor was presumed to be positive for HPV based on P16 testing. P16 is an indirect measure of HPV with a 90% sensitivity . PositroOn physical examination prior to the start of treatment, Mr. D was in no apparent distress and had a pleasant disposition. Neurologic examination was unremarkable, with pupils equal and reactive to light, extraocular movements intact, and cranial nerves II through XII grossly intact. He was unable to breathe through his nose. He was also unable to taste or smell. Nasopharyngolaryngoscopy was aborted due to complete obstruction of the nasopharynx. Visualization of the posterior oropharynx was also limited due to tumor partially obstructing the posterior oropharynx. No cervical, supraclavicular, or axillary adenopathy was noted. Lungs were clear to auscultation with equal breath sounds. Cardiac exam revealed a regular rate and rhythm, no murmurs or rubs. His abdomen was soft, nontender with positive bowel sounds. The extremities revealed no edema, 5/5 strength and +2 deep tendon reflexes in all extremities, and no spinal tenderness to palpation.2 every 3 weeks and IMRT to a total dose of 70 Gy to the primary tumor and bilateral neck over 7 weeks. The treatment field for IMRT extended from the base of the skull down to the level of the clavicles with bilateral neck fields. Given the treatment field, Mr. D was anticipated to experience grade 3 mucositis of the nasopharynx and oropharynx.Mr. D was not a surgical candidate. As a result, he received definitive treatment with cisplatin 100 mg/mTo prevent pain in Mr. D’s case, gabapentin was initiated at the beginning of week 2 of treatment prior to the development of significant mucositis. By week 4 of treatment, he had grade 3 mucositis of his palate bilaterally as well as his pharyngeal wall, base of tongue, and epiglottis. Mr. D reported intermittent mild pain (maximum rating of 3/10 in the last 2 weeks of treatment) in his throat, described as sharp in quality. This pain description was reported throughout his treatment and recovery period.Mr. D repeatedly declined opioids but stated that he had no opposition to using them if needed. Although the decision was made not to place a prophylactic feeding tube, Mr. D developed a metallic taste in his mouth that interfered with his ability to eat. As such, he lost more than 10% of his body weight during treatment and required placement of a percutaneous feeding tube . HoweverThe use of gabapentin to prevent pain was considered successful in Mr. D’s case. Given the size of his radiation field and the dose of radiation received, it is unusual for a patient not to require any opioids during or after treatment. Patients undergoing this treatment frequently experience moderate to severe pain due to oral mucositis, requiring significant doses of opioids to control their pain and maintain oral intake or the ability to maintain some swallowing function. Other measures such as topical lidocaine and rinses containing a mixture of medications that vary among institutions (often referred to as Magic Mouthwash) are also used, yet topical measures are generally inadequate to control pain without the addition of systemic opioids.In addition, patients are at risk for infection due to bone marrow suppression from chemotherapy. Aspiration pneumonia is also a risk for these patients. This is due to the presence of a large amount of thick saliva caused by irritation of the salivary glands as well as decreased sensitivity of the throat to aspiration, as a result of the radiation. Therefore, NSAIDs are not an ideal pain intervention for this group of patients, as they will mask fevers that would otherwise indicate a potential infection. Gabapentin seems to be an ideal medication for the prevention and treatment of pain due to mucositis caused by treatment with chemotherapy and radiation therapy. Gabapentin is not highly protein-bound or metabolized by the liver; therefore, significant drug interactions are not anticipated. The majority of the medication is excreted unchanged by the kidneys .Gabapentin is started at 600 mg at bedtime and escalated over a period of 6 days. Ideally, patients are titrated to a dose of 1,800 to 2,700 mg of gabapentin in divided doses every 8 hours from the start of week 2 of treatment prior to the development of painful mucositis. The dose is escalated slowly over a week to avoid unwanted side effects such as sedation and/or dizziness. Dosing is modified for patients 65 or older due to the potential for greater side effects in elderly patients . PatientPatients are monitored for the most common adverse events such as sedation, dizziness (anticipated to be transient in nature), impaired cognition, nausea, swelling of the lower extremities (unrelated to cardiac function), and rash. While chemotherapy is more commonly associated with rash, there is a risk of Stevens-Johnson syndrome with all AEDs; therefore, any generalized rash will result in the discontinuation of gabapentin. Other side effects listed in the package insert are much less common.Education regarding gabapentin for the patient and family member includes the purpose of the medication, common side effects, dosing schedules, and other interventions that may be utilized if the AED is insufficient to treat the pain experienced by the patient. The need to begin the medication prior to the development of pain is stressed to patients, as it has been demonstrated that gabapentin exerts its effect best prior to the development of new synapses .Patients undergoing treatment for head and neck cancer experience considerable pain during and following treatment. Gabapentin and pregabalin have a potential role in pain prevention for these patients. These medications have the following actions that may decrease pain due to cancer or its treatment:Inhibition of the actions of the A₂ subunit protein (α2δ1)Inhibition of glutamate releaseInhibition of the activity of NMDA receptorsInhibition of the activity of voltage-gated sodium channelsEnhancement of the activity of voltage-gated potassium channelsInhibitory processes are enhanced, potentially resulting in a decreased incidence of chronic pain, after prolonged exposure . The actHead and neck cancer and its treatment frequently result in the development of pain. A large body of literature exists on the best way to treat pain once it occurs. However, literature suggesting that there may be a way to alter how the body transmits painful stimuli in some cases is emerging. This may be accomplished by altering the microenvironment between cells, thereby decreasing the transmission of painful impulses using AEDs. In some cases, this may be best accomplished prior to the development of pain.The previous discussion outlined the use of gabapentin in head and neck cancer and pregabalin in the surgical population prior to the development of pain as well as the use of the agents in achieving some degree of preventive analgesia. Future research is needed to demonstrate the effectiveness of this class of medications in pain prevention for patients expected to experience pain as a result of cancer and/or its treatment. Studies may include a direct comparison to standard therapy and determination of the appropriate population, as well as ideal dosing and schedules for both gabapentin and pregabalin.


Neck pain is one of the most common reasons for entry into the healthcare system. Recent increases in healthcare utilization and medical costs have not correlated with improvements in health. Therefore there is a need to identify management strategies for neck pain that are effective for the patient, cost efficient for the payer and provided at the optimal time during an episode of neck pain.One thousand five hundred thirty-one patients who underwent physical therapist management with a primary complaint of non-specific neck pain from January 1, 2008 to December 31, 2012 were identified from the Rehabilitation Outcomes Management System (ROMS) database at Intermountain Healthcare. Patients reporting duration of symptoms less than 4 weeks were designated as undergoing “early” management and patients with duration of symptoms greater than 4 weeks were designated as receiving “delayed” management. These groups were compared using binary logistic regression to examine odds of achieving Minimal Clinically Important Difference (MCID) on the Neck Disability Index (NDI) and Numerical Pain Rating Scale (NPRS). Separate generalized linear modeling examined the effect of timing of physical therapist management on the metrics of value and efficiency.Patients who received early physical therapist management had increased odds of achieving MCID on the NDI  and MCID on the NPRS , when compared to patients receiving delayed management. Patients who received early management demonstrated the greatest value in decreasing disability with a 2.27 percentage point change in NDI score per 100 dollars, best value in decreasing pain with a 0.38 point change on the NPRS per 100 dollars. Finally, patients receiving early management were managed more efficiently with a 3.44 percentage point change in NDI score per visit and 0.57 point change in NPRS score per visit.These findings suggest that healthcare systems that provide pathways for patients to receive early physical therapist management of neck pain may realize improved patient outcomes, greater value and higher efficiency in decreasing disability and pain compared to delayed management. Further research is needed to confirm this assertion. The majority of healthcare in the United States is delivered in a fee for service (FFS) model and this delivery model has likely contributed to the uncontrollable rise in healthcare costs in the United States –3. UnderRecent research supports that early physical therapist management for low back pain is recommended to improve outcomes in comparison to other management pathways such as advanced imaging, prescription medication or advanced care , 9, and Neck pain is one of the most common reasons for entry into the healthcare system  and disaThe purpose of the study was, therefore, to provide foundational information for determining the value proposition of early physical therapist management of neck pain. To address this purpose, we compared the odds of achieving a meaningful reduction in disability and pain and we compared the metrics of value and efficiency between patients receiving early physical therapist management and delayed physical therapist management to determine the impact of timing of physical therapist management. We hypothesized that patients who received physical therapist management earlier during an episode of neck pain would have the best odds of clinical improvement and the greatest value and efficiency for decreasing disability and pain.Data for this retrospective cohort analysis was extracted from the Rehabilitation Outcomes Management System (ROMS). This rehabilitation database contains demographics, patient characteristics, clinical outcomes and rehabilitation utilization data that is maintained by Intermountain Healthcare, a private, non-profit integrated healthcare system. The study protocol was approved by the Institutional Review Board of Intermountain Healthcare.Patients included in this study received physical therapist management for the primary complaint of neck pain between dates January 1, 2008 to December 31, 2012 from 13 outpatient physical therapy clinics located in Salt Lake City, Utah and surrounding regions. Inclusion criteria for these analyses were: non-surgical patient, Neck Disability Index (NDI) score of 10 or greater and Numerical Pain Rating Scale (NPRS) score of 2 or greater at initial evaluation, 2 or more visits, duration of physical therapist management of less than 180 days and have a self-reported primary complaint of non-specific neck pain. The inclusion criteria were implemented to permit the evaluation of clinical outcomes , 25 thatAt initial evaluation, patients reported their primary complaint and neck pain symptom duration. This information was recorded by the physical therapist and entered into the ROMS database. Patients utilized in this analysis were identified in the ROMS database if they self-reported non-specific neck pain as their primary complaint. The patients were categorized as receiving “early physical therapist management” of neck pain if they reported non-specific neck pain with duration less than 4 weeks and “delayed physical therapist management” if they reported non-specific neck pain duration greater than 4 weeks. This categorization is supported in the low back pain literature where early physical therapist management has been defined as management within 2 weeks , 11 or wThe primary clinical outcome measures used in these analyses were the Neck Disability Index (NDI) and the Numerical Pain Rating Scale (NPRS). The NDI is a condition specific outcome measure that is a commonly used outcome measure for people with neck pain and is the most studied and well-established of all the outcome measures for neck pain  and it iIn order to determine whether patients experienced a meaningful improvement the Minimal Clinically Important Difference (MCID) was calculated for the NDI and NPRS. MCID values assist in determining the minimal amount of change that represents a clinically important difference for the patient. The most rigorous estimate of MCID for the NDI for patients with neck pain has been reported as a 19 percentage point change (9.5 raw score). Other estimates of MCID for patients with neck pain include a 10 percentage point change (5 raw score)  and 15 pNext, we wanted to determine the value proposition of early physical therapist management of neck pain by examining the metrics of value and efficiency. Value is defined as the change in outcome per dollar. In this study, we calculated two value metrics using the changes in NDI and on the NPRS during an episode of physical therapy. The metric of value for disability was calculated by dividing the change score on the NDI  during an episode of care by the total charges for physical therapy multiplied by 100 during an episode of care ((Change in NDI/Charges for PT) x100)). This calculation allows for the interpretation of change in disability per 100 dollars. The metric of value for pain intensity was calculated by dividing the change score on the NPRS  during an episode of care by the total charges for physical therapy multiplied by 100 during an episode of care ((Change in NPRS/Charges for PT) x100)). Smaller numbers indicate lower value and larger numbers higher value.A variable for efficiency of physical therapist management of neck pain for decreasing disability was also calculated and has been previously reported for musculoskeletal conditions . The autDescriptive statistics and clinical characteristics were calculated for all patients in this sample. Means and standard deviations were reported for normally distributed continuous variables, median and interquartile range for number of visits and percentages were reported for categorical variables. Baseline patient characteristics, clinical outcomes and utilization of physical therapy were compared among timing groups using chi-squared analyses for categorical variables and independent t-tests for normally distributed continuous variables or Mann Whitney U tests for non-normally distributed continuous variables.The main outcomes of interest in this study were the odds of patients achieving MCID on the NDI and NPRS and the metrics of value and efficiency. Model selection for all analyses were performed using an initial set of potentially confounding variables based on previous literature on prognostic factors for neck pain such as age and gender  and concBoth unadjusted and adjusted analyses were performed with separate binary logistic regression models to compare the odds of achieving MCID on the NDI and the NPRS between patients receiving early physical therapist management and delayed physical therapist management. Covariates in the initial adjusted models included age, gender, and duration of treatment, number of visits and baseline NDI and NPRS scores. All covariates were retained in the final model with the exception of baseline scores on the NDI in the model estimating MCID on the NPRS and baseline scores on the NPRS in the model estimating MCID on the NDI. Odds ratios with 95 % confidence intervals were reported.Separate generalized linear regression models, normal distribution with identity link function, were estimated to compare the value for disability and value for pain between patients receiving early physical therapist management and delayed physical therapist management. Covariates in the initial models included age, gender, number of visits, duration of treatment and baseline scores for the NDI and NPRS. All covariates were retained in the final model when estimating value for disability and when estimating value for pain, with the exception of baseline scores on the NDI, all covariates were retained in the final model. Separate generalized linear regression models, normal distribution with identity link function, were estimated to compare the efficiency of physical therapist management for both change in disability and change in pain per visit between patients with receiving early physical therapist management and delayed physical therapist management. Covariates in the initial models included age, gender, duration of treatment and baseline scores for NDI and NPRS. In the final models estimating efficiency for change in pain and change in NDI the covariates included age, gender, admission NPRS score and duration of treatment and baseline score of outcome of interest. Estimates of means and 95 % confidence intervals between groups were reported. Data analysis was performed using SPSS statistical software (version 21.0). Significance level for all analyses was set at 0.05.One thousand five hundred thirty-one patients with non-specific neck pain were identified from the database after exclusion criteria were met. See Fig. The odds of achieving MCID or the amount change on an outcome measure that needs to occur for a patient to identify as important is reported in Table Patients who received early physical therapist management demonstrated better value in decreasing disability and pain compared to patients who received delayed physical therapist management. When controlling for covariates, patients receiving early physical therapist management demonstrated a 2.27 percentage point change  in disability score per 100 dollars compared to patients who received delayed physical therapist management who demonstrated a 1.22 percentage point change in NDI per 100 dollars spent . Patients who received early physical therapist management also demonstrated a greater change in pain per 100 dollars  compared to patients who received delayed physical therapist management .Patients who received early physical therapist management also experienced more efficiency in reducing disability and pain with physical therapist management of neck pain. The patients who received early physical therapist management achieved a 3.44 percentage point change in NDI score per visit  and 0.57 point change  in pain compared to a 1.81 percentage point change  in NDI score and 0.42 point change  in pain per visit when patients received delayed physical therapist management. Both adjusted and unadjusted mean estimates and 95 % CI are reported in Table Improving value in musculoskeletal healthcare has emerged as an important objective and the Institute of Medicine (IOM) has made the recommendation that the public at large and people with pain, in particular, would benefit from a better understanding of pain and its treatment, in order to encourage timely care and improve medical management . MoreoveThe indirect costs for patients with neck pain can potentially supersede the direct costs to the healthcare system. A study in the Netherlands found that direct costs, such as healthcare, amounted to just 23 % of this figure while indirect costs, such as work absenteeism and disability, amounted to 77 % of the total costs . In thisWhen investigating the value of early physical therapist management of neck pain from the payer perspective, our findings are consistent with the literature which reports that earlier physical therapist management of spine pain can lead to less resource utilization , 39, 45.From the provider perspective, this study supports that the most efficient care can be provided when a patient is seen within the first four weeks of symptoms in order to experience the greatest decreases in their disability and pain. Bridging these findings with the patient perspective, this means it takes approximately half the number of visits when patients receive early physical therapist management to achieve a meaningful reduction (ie MCID) on the NDI and NPRS compared to patients who receive delayed management to achieve the same decrease in disability on the NDI and NPRS. Some may argue that patients receiving early physical therapist management of neck pain, may have different care seeking behavior due to experiencing more severe symptoms or simply this group experienced a regression towards the mean that accounted for the greater change in score compared to delayed physical therapist management. Although patients who received early physical therapist management had higher baseline NDI scores, the difference in the NDI scores between groups did not exceed error  nor wereThere are strengths in the current study. The concept of value proposition of early physical therapist management of neck pain was discussed from three perspectives: the patient, payer and provider. The benefit of early physical therapist management was potentially realized from all stakeholders. The policy implications of these findings provide support for early physical therapist management of neck pain. An additional strength of the study was the introduction of the metric of value specifically related to physical therapist management of neck pain. The metric of value calculated in this study is consistent with the definition of value in healthcare services, where value is defined the health outcomes achieved per dollar . We examThere are also limitations in the current study. The authors discuss the value of early physical therapist management of neck pain, not value of early physical therapist management of neck pain and its effect on downstream healthcare costs and utilization. Although this is a limitation, recent research in low back pain supports that providing early physical therapist management after consultation with a primary care provider was not associated with an increase in costs or utilization of specific services . TherefoFurther research in needed to examine the effect of early physical therapist management of neck pain relative to downstream costs and utilizations and to make specific recommendations on interventional strategies based on timing of physical therapist management of neck pain.Policy makers and payers contribute to the value equation by designing health policies that promote access and use of timely, appropriate healthcare services . In thisaOR, Adjusted odds ratio; FFS, Fee for service; IOM, Institute of Medicine; MCID, Minimal Clinically Important Difference; NDI, Neck disability index; NPRS, Numerical Pain Rating Scale; NSNP, Non-specific neck pain; OR, Odds Ratio; PT, Physical Therapy; USD, United States Dollar.


Postoperative pain is considered as a reason of patient’s delay in discharge and disability aggravation. Therefore, multimodal approaches have been suggested in order to mitigate pain and decrease postoperative side effects.The aim of this study was to evaluate analgesic effect of a single dose injection of dexamethasone on reducing postoperative pain in laparoscopic cholecystectomy.In this double-blind, prospective study, 122 patients aged 18-60 years old, whom were selected for laparoscopic cholecystectomy, were classified into two case and control groups, and 61 patients were included in each group. The case (D) group underwent general anesthesia and a single- dose intravenous injection of dexamethasone. The Control (C) group received general anesthesia and intravenous injection of normal saline. Total dose of consumed meperidine and pain intensity during first 24 hours were evaluated in both groups.No significant difference existed between two groups regarding age, sex, weight and operation time. Pain intensity in group D was significantly less than group C (P < 0.01) after two, six and 12 hoursof surgery. No significant difference existed in pain intensity between two groups at the beginning of and 24 hours after the surgery (P > 0.05). Meperidine consumption in group D was significantly less than group C (P < 0.05).Findings of present study showed that single dose of intravenous dexamethasone, led to less pain intensity and amounts of meperidine consumption, in comparison with placebo. One the most important causes of patient’s illness after surgery is induced surgical trauma pain that can lead to chronic postoperative pain . AlthougPrevious studies showed that preemptive analgesia causes attenuation of signals entering spinal cord, which is much more effective than controlling pain after its induction . DiffereThe aim of this study was to investigate the effect of single- dose intravenous dexamethasone administration on postoperative pain in patients undergoing laparoscopic cholecystectomy.This was a clinical double- blind, prospective study, carried out between 2012 and 2013. All of patients in case and control groups were selected from patients referred to Razi hospital in Ahvaz- Iran.After proposal approval by ethical committee of Ahvaz Jundishapur University of Medical Sciences and obtaining informed consent and patients training by verbal explanation regarding how to assess pain intensity on visual analogue scale (VAS), 122 patients whom were candidate for laparoscopic cholecystectomy, aged 18-60 years, with American Society of Anesthesiologists (ASA) classes I and II were selected. Patients with hepatic and renal insufficiency, history of corticosteroid hypersensitivity, previous gastric ulcer, receiving corticosteroids or immunosuppressive drugs, diabetes mellitus, and receiving analgesics and opioids were excluded. Afterward, subjects were divided into two groups of 61 patients completely randomly with computer-generated list of random numbers.2 and achieving intra-abdominal pressure of 14 mmHg. Patients received remifentanil (0.1 µ/kg/min) and propofol (50 µ/kg/min) as maintenance dose, to maintain anesthesia. Patients were reversed by neostigmine (0.05 mg/kg) and atropine (0.02 mg/kg). Both anesthesiologist and patients were not aware of performed classifications.After electrocardiographic monitoring, pulse oximetry, blood pressure measurement, capnography, and hydration with 10 mL/Kg of crystalloids in all subjects, general anesthesia was induced with midazolam (0.05 mg/Kg), fentanyl (2 µ/kg), sodium thiopental (5 mg/kg), and atracurium (0.5 mg/kg). Group D received 0.1 mg/kg (up to 8 mg) of dexamethasone, and group C received 2 ml of normal saline after anesthesia induction. At beginning of the surgery, four trocars were placed into the abdomen and surgical procedure initiated right after injection of COThe post-operative pain intensity was measured with intervals of zero, two, six, 12 and 24 hours after entrance to postanesthesia care unit (PACU) by VAS, in which the minimum pain score is zero and the most severe pain that can be imagined is 10. A resident of anesthesiology, who was not aware of patient’s drug group, carried out these evaluations using a questionnaire. If pain score was equal or more than three, 0.2 mg/kg of meperidine was administered intravenously, and total consumed meperidine during 24 hours was recorded.Considering power of 80% and confidence interval (CI) of 95%, sample size was calculated as 61 samples for each group; therefore, 122 samples as a whole were included by NCSS software, based on variance analysis for repeated samples. All of the statistical data were reported as mean ± SD. After data collection, they were analyzed using SPSS version 18 software. To compare mean pain values in either case or control groups, independent samples t-test; and to compare pain scores at different hours square t-test and test of repeated measurements were applied. Significance of data was considered as P < 0.05.In the present study 122 patients were divided into two groups receiving placebo (C) and dexamethasone (D). There was no excluded patient. According to the results in According to the results in Results of present study revealed that intravenous single-dose of dexamethasone can reduce postoperative pain at first 12 hours in comparison with placebo. The intravenous single-dose dexamethasone can also decrease total consumed analgesic. Lim et al. found that intravenous injection of dexamethasone before and after laparoscopic cholecystectomy has been effective in reducing postoperative pain . Also, sNevertheless, Elhakim et al. showed that while the intravenous dexamethasone was effective in reducing postoperative nausea and vomiting, it was not effective in case of postoperative pain . Pain afSince multiple factors are considered for postoperative pain, application of approaches that leads to short- term analgesia cannot cause functional improvement and reduction of the length of hospitalization; hence, the multimodal approaches are considered , 9. Beca Strong anti-inflammatory properties of dexamethasone have caused to introduction of “dexamethasone induced postoperative pain reduction” theory. Although analgesic mechanism of dexamethasone is still unclear, it seems that a decrease in cyclooxygenase and lipoxygenase production, via inhibition of peripheral phospholipase, plays a main role , 17.While long- term consumption of steroids is associated with some side effects such as increased risk of wound infection, delayed wound healing, adrenal suppression and glucose intolerance, their single-dose administration is safe , 13. PerThe study showed that time of dexamethasone injection is important on reducing postoperative pain as well; since initiation of its biological effect is one to two hour after injection . In our Laparoscopic cholecystectomy is one of selective surgical approaches for cholecystitis, which is done frequently. Therefore, achieving sufficient analgesia for this procedure is very important. Regarding the present study, it seems that intravenous single-dose dexamethasone can reduce postoperative pain and opioid consumption.


The mean increment in PSFS score of the ISWIgroup was 2.9±2.2 1 day after treatment, while that in the control group was 0.9±2.2.Our study showed that ISWI was effective for relieving pain and improving function inaLBP patients at short-term follow-up. ISWI might be an alternative treatment foraLBP patients, especially in areas where medications are not available, as well as inspecific patients , who are unable toreceive medications or other forms of analgesia because of side effects.Intracutaneous sterile water injection (ISWI) is used for relief of low back painduring labor, acute attacks of urolithiasis, chronic neck and shoulder pain followingwhiplash injuries, and chronic myofascial pain syndrome. We conducted a randomized,double-blinded, placebo-controlled trial to evaluate the effect of ISWI for relief ofacute low back pain (aLBP). A total of 68 patients  between18 and 55 years old experiencing aLBP with moderate to severe pain  were recruited and randomly assigned to receiveeither ISWIs (n=34) or intracutaneous isotonic saline injections . The primary outcome was improvement in pain intensity using the VAS at 10, 45,and 90 min and 1 day after treatment. The secondary outcome was functionalimprovement, which was assessed using the Patient-Specific Functional Scale (PSFS) 1day after treatment. The mean VAS score was significantly lower in the ISWI groupthan in the control group at 10, 45, and 90 min, and 1 day after injection(P<0.05,  Low back pain is one of the most common problems presenting in primary care and is themost commonly reported type of pain worldwide 2345.The principal clinical goals of treatment for aLBP are to relieve pain, reduce time awayfrom work, improve physical functioning, develop coping strategies through education,and diminish the likelihood of developing chronic low back pain. A wide range ofpharmacological and non-pharmacological therapeutic treatments are available for aLBP,but their benefits and effectiveness still need to be verified 910. ThSeveral studies have demonstrated that intracutaneous sterile water injection (ISWI)provides statistically and clinically significant pain relief in women who experiencecontinuous lower back pain during labor 171819Therefore, the present study aimed to determine whether ISWI is an effective method ofameliorating aLBP, especially for those who do not want, are unsuitable for, or do nothave access to other pain therapies.This study was a randomized, placebo-controlled, double-blinded, clinical trial thatevaluated the efficacy and safety of ISWI for the treatment of aLBP. This trial wasconducted from March 2012 to February 2013. The randomization scheme wascomputer-generated and completed prior to the start of the study. The patients wererandomly allocated to either the experimental group or control group at a ratio of1:1. Experimental group patients received ISWI in the lumbosacral regions, whilecontrol group patients received corresponding intracutaneous injections of isotonicsaline. We obtained the outcome variables at five different times: before treatment,at 10, 45, and 90 min, and 1 day post-treatment.Written informed consent was obtained from each participant. The study was approvedby the Ethics Committee of Lianyungang No.1 Hospital. We offered no economicincentives to the participants, and the patients were not billed for the treatment.The participants and treating clinician were blinded to treatment allocation.The patients  included in this study were recruited from theFirst People’s Hospital of Lianyungang City, located in Jiangsu Province. Theeligibility criteria for this trial were as follows: aLBP that was localized betweenthe costal margin and above the inferior gluteal folds without radiating pain to thelimb; aged between 18 and 50 years with aLBP of <2 weeks duration; the firstepisode of aLBP; and moderate to severe aLBP . Exclusion criteriawere as follows: aLBP attributed to known or suspected serious pathology ; presumptive orconfirmed lumbar nerve root compression; previous spinal surgery; pregnancy; patientswho received any analgesic treatment within 12 h prior to recruitment in the study;experience of any side effects after taking NSAIDs; and reluctance or inability tocomplete the questionnaire.The sample size was estimated using the mean difference in VAS scores for aLBPbetween the experimental and control groups. Based on previous pilot studies, thedifference in the mean change in VAS score between the two groups was 2.2. Weconservatively set this value as 2. When a two-tailed test with a test power of 80%and significance level of 5% was used, the minimum number of participants requiredfor each group was 31 participants. To allow for 10% loss in follow-up, a total of 68participants were required.The intracutaneous injection technique and examination of injection sites of allpatients were conducted by the same pain specialist, who had >20 years of clinicalexperience. The injection sites consisted of all tender points (defined as feelingtender to pressure) and trigger points (defined as feeling tender and a radiatingsensation when pressed). The location of each injection point was determined inaccordance with previous studies and clinical experience ,26. Tend¯,Germany) with a thin needle  wasused for injections. After the needle was disinfected with alcohol, 0.5 mL sterilewater or isotonic saline was injected to create blebs at the injection site. Three tofive injections were administrated in rapid succession, emptying the syringe . The injections of sterile water caused a briefstinging sensation lasting for approximately 20 s  at baseline and on the 1st day post-injection ,29.The One day after treatment, the patients were asked to rate their global rating ofchange on a 7-point Likert scale with responses of 1="completely gone", 2="muchbetter", 3="better", 4="a little better", 5="about the same", 6="a little worse", and7="much worse" ,31. The The number of participants using intramuscular injections of parecoxib sodium foradditional treatment and the number of adverse events at day 1 post-injection wererecorded. On the first post-injection day, the patients were asked to complete aquestionnaire regarding whether they would accept the same treatment during a futureepisode of aLBP.t-test andthey are reported as means±SD. Categorical variables were compared using thechi-square test or Fisher’s exact test and are reported as numbers or percentages.Furthermore, the Mann-Whitney U test was used if the normality assumption wasviolated. For comparison of the VAS, PSFS, global rating of change, and satisfactionwith intervention between the two groups, the independent t-test orMann-Whitney U test was used. The percentage of participants using intramuscularinjection of parecoxib sodium for additional treatment, the percentage of adverseevents, and the percentage of participants who accepted the same treatment during afuture episode of aLBP in each group were calculated and compared using thechi-square test or Fisher’s exact test. Two-tailed tests at a significance level of0.05 were used. All statistical analyses were performed using SPSS version 16.0software .Continuous variables were compared using the independent A flowchart of the study is shown in 2. Atotal of 41 of 68 (60.1%) patients were women. A total of 29 of 68 (42.6%) patientsclaimed to perform regular physical exercise, and 40 of 68 (58.8%) patients weremarried. No significant differences in age, BMI, sex, regular physical exercise, andmarital status were observed between the two groups. At baseline, the mean rating ofpain intensity score was 6.7 for the experimental group and 6.6 for the controlgroup, with no difference between the groups (P=0.919). The median duration ofcurrent aLBP episodes in participants at the time of enrollment was 5.4 days. Therewas no significant difference in the PSFS score and the number of injection sitesbetween the two groups  than the control group . Thissignificant difference in the VAS was maintained at all other follow-up examinationtimes .There was a significant reduction in VAS score at 10 min after treatment comparedwith that at baseline in both groups, but this difference was more pronounced in theexperimental group (P<0.001). The mean VAS score was also significantly morereduced in the experimental group compared with the control group at 45 min(P<0.001), 90 min (P<0.001), and 1 day post-treatment (P=0.029). The meandifference in the pre- and post (10 min)-injection VAS score between the two groupswas 2.2 points  in favor of theexperimental group. This finding indicated that, on average, ISWI induced a greaterreduction in pain than did intracutaneous injections of isotonic saline. Thisdifference was also observed at 45 min, 90 min, and 1 day post-treatment .The mean PSFS 1 day after treatment was significantly higher than the pretreatmentscore (P<0.001) in both groups. The PSFS score 1 day after treatment in theexperimental group (6.2±1.8) was significantly higher compared with that in thecontrol group . The mean increment in PSFS score on a 0 to 10scale in the experimental group was 2.9±2.2 1 day after treatment, while the meanincrement in the control group was 0.9±2.2. The mean difference in increment of thePSFS score between the two groups was 2.0 points in favor of the experimental group.For the patients’ global impression  of the treatment, therewas a significant difference between the two groups as follows. The experimentalgroup showed a higher level of satisfaction with the treatment (6.6±2.0) than did thecontrol group  using parecoxib for theiradditional pain relief subsequent to sterile water injection was not significantlydifferent from that in the control group . More patients in theexperimental group (64%) claimed that they would want to use the same pain reliefmethod in a future episode of aLBP than those in the control group .No serious adverse events were observed during the trial in either group. The onlycomplaint reported in the trial was transient burning pain at the injection sites,and this pain lasted approximately 20–30 s. A higher percentage of patients in theexperimental group  reported transient burning pain than did the controlgroup .This study shows the safety and efficacy of ISWI versus placebo  inpatients with aLBP. ISWI provided a higher degree of pain relief and functionalimprovement than did placebo injections. These results suggest that ISWI has superioreffects on reduction of pain and improvement in functional status, as shown by the VASscores of aLBP and PSFS scores, compared with isotonic saline injection.Our study also indicated that intracutaneous isotonic saline injections had asignificant effect in reducing pain and increasing function. This finding is inagreement with previous observations during pain research in which placebo managementhad a considerable analgesic potency ,26. The In aLBP, sometimes there is a brief "hyperacute" period of 24-48 h during which patientsare essentially immobilized and motion is hampered by pain and intense spasm.Fortunately, this hyperacute period occurs in a small amount of patients and generallyresolves within 24-48 h . In our As previously reported, transient intense pain associated with administration negativelyaffects patients’ experiences of ISWI ,19,20,22Recently reported clinical trials have focused on the practicality of ISWI for differentpain syndromes. However, the results of these trials are not concordant. In accordancewith the results of pain in our study, ISWI has been reported to relieve acute laborpain, acute renal colic pain, neck and shoulder pain in whiplash syndrome, and chronicmyofascial pain syndrome 232425An important strength of this study is that interventions were performed by the sameexperienced clinician who was blind to the group allocation and outcome measures.Additionally, the participants and the outcome investigator and analyst remained blindedto treatment allocation throughout the study. A further strength of our study was thesmall overall loss to follow-up (<5%).The primary limitation of this study was the fact that we did not include a controlgroup without treatment. Therefore, we cannot make conclusions about "absolute"treatment effectiveness for ISWI or isotonic saline. Clinically significant results maydiffer from statistically significant results. Previous studies have reported that areduction in VAS score of ≥3.5 and improvement in PSFS score of ≥2 are clinicallysignificant in low back pain patients ,39. In oIn future studies, the maximum duration of pain relief and the effectiveness of repeatedinjections of sterile water in patients with aLBP should be determined. The optimaltissue depth for injection and the volume of sterile water to be injected should also beprecisely defined. The use of subcutaneous injections to reduce the intense burning painassociated with intracutaneous injections and evaluation of the effects of subcutaneoussterile water injections on aLBP could be considered for future studies. Finally, futurestudies should also establish the treatment effect of ISWIs on aLBP in actual clinicalpractice. Currently, there are few data to support whether a subgroup of individuals aremore likely to benefit from this method. Therefore, stringent eligibility criteria ofthe study may be an important consideration for future clinical applications.Our data showed that ISWI was effective in ameliorating pain and improving function inaLBP patients. This procedure is safe, easy to perform, inexpensive, and suitable foralmost everyone. This method may be suitable for patients with moderate to severe aLBPincluding those who are too old or too young for other treatments, who may not haveaccess to medications, those who are purposely trying to avoid other forms of analgesiabecause of perceived or actual side effects, and those in rural and remote areas or insome developing countries.


Although various analgesics have been used, postoperative pain remains one of the most troublesome aspects of tonsillectomy for patients.The aim of the present study was to evaluate the effectiveness of premedication using pregabalin compared with placebo (diazepam) on postoperative pain control in patients undergoing tonsillectomy.P < 0.05 was considered statistically significant.Forty-eight adult patients were randomly divided into a control group and a pregabalin group. Preoperatively, patients in the control group received 4 mg diazepam orally as placebo, whereas those in the pregabalin group received 300 mg pregabalin orally. All participants were provided with patient-controlled analgesia using fentanyl for 24 hours after surgery. Postoperative pain treatment included acetaminophen 650 mg three times daily for 8 postoperative days. The primary outcome measure was the total amount of patient-controlled fentanyl consumption after tonsillectomy. Secondary outcome measures were the number of injections of ketorolac tromethamine (each 30 mg) requested by patients, pain scores, overall satisfaction scores, drowsiness, nausea, dizziness, headache, and vomiting after the surgery. P < 0.001). There were no significant differences in the number of ketorolac tromethamine injections, pain scores, overall satisfaction scores, drowsiness, nausea, dizziness, headache, and vomiting between the two groups.The total amount of fentanyl demanded decreased significantly in the pregabalin group (Administration of 300 mg pregabalin prior to tonsillectomy decreases fentanyl consumption compared with that after 4 mg diazepam, without an increased incidence of adverse effects.KCT0001215 Tonsillectomy is one of the most common surgical procedures performed in otorhinolaryngology. However, postoperative pain following tonsillectomy is one of the most difficult to manage in this area of surgery. The severe pain from a tonsillectomy can delay the recovery process and extend the hospital stay . TherefoRecent advances in the pathophysiology of pain have suggested that it is possible to prevent or attenuate the central neural hyperexcitability that contributes to enhanced postoperative pain ,4. Pregahttp://cris.nih.go.kr/cris/index.jsp, registration number: KCT0001215). The purpose and method of the research were explained to the patients before the surgery, and written consent was obtained. The protocol for this trial and supporting CONSORT checklist are available as supporting information; See The study was approved by Institutional Review Board of Incheon St. Mary’s Hospital (IRB Number: OC10MISE0025) and the Korean Food and Drug Administration (KFDA). It was registered at clinical research information service, republic of Korea  allergy to drugs in the study, (2) alcohol or drug abuse, (3) treatment with antidepressant or antiepileptic medication within 4 weeks of the operation, (4) pregnant or breastfeeding patients, (5) tonsillar malignancy, (6) impaired kidney function, or (7) daily intake of analgesics or intake of any analgesic within 24 hours of surgery.TM, Abbott Laboratories, Illinois) with the same parameters , and the total amount of injected fentanyl was recorded before discharge. Additionally, 30 mg of ketorolac tromethamine was injected intramuscularly at the patient’s request, and the number of ketorolac tromethamine injections was recorded. The grade of pain was self-assessed by the patients using a visual analogue scale (VAS) that ranged from 0 (no pain) to 10 (most severe pain). The pain grade during resting periods (rVAS) and during swallowing (sVAS) was assessed at 1, 2, 4, 8, 12, and 24 hours postoperatively, and then daily for 7 days after discharge. Each patient was questioned regarding their overall satisfaction with the analgesic effects during the first 24 hours after surgery and again 8 days after surgery . Possible side effects of the medications, including drowsiness, nausea, dizziness, headache, and vomiting, were assessed and recorded in the patient’s medical chart during the 24 hours following tonsillectomy.Prior to surgery, we explained the goal of this study to all patients, who were then educated in the use of the visual analogue scale (VAS) chart and the use of a patient-controlled analgesia (PCA) pump. The night before and 1 hour before surgery each patient received either a 150 mg capsule of pregabalin   or a 2 mg capsule of diazepam orally . General anesthesia was induced with intravenous propofol (2 mg/kg) and tracheal intubation was facilitated with intravenous rocuronium bromide (0.6 mg/kg). Anesthesia was maintained with sevoflurane and 50% nitrous oxide in oxygen. Paralysis was reversed with glycopyrrolate and pyridostigmine at the end of surgery. Tonsillectomy was performed using the same technique for all patients, including monopolar electrocautery; bleeding was controlled using simple compression, bipolar electrocautery, and topical application of hydrogen peroxide. As a basic analgesic regimen, both groups were given acetaminophen 650 mg three times daily  for 8 postoperative days. While in the hospital, patients in both groups were supplied with 1% fentanyl that was administered via a PCA device  test. Descriptive statistics were obtained to determine the influence of each group’s clinical parameters on the results. A χ2 test and a t-test were conducted to assess the differences in the clinical characteristics of the two groups. A Mann—Whitney U-test or t-test was used to analyze overall differences between groups. We used the t-test to analyze the differences in each variable between groups at each designated monitoring point of the follow-up period. Repeated measures ANOVA was used to analyze the interaction between time and group for each variable. For evaluation of side effects such as drowsiness, nausea, dizziness, headache, and vomiting, Fisher’s exact test comparing the two groups was used.Results are presented as the mean ± standard error. Fifty patients were included and were randomly assigned to a group. Two subjects were considered dropouts after initial randomization (both withdrew) and were therefore not subjected to further statistical analysis. Consequently, 48 patients were included in the final analyses . As showP < 0.001) (P = 0.24). We found a trend to a decrease in rVAS over time within the first 8 days postoperatively (P = 0.04), even though there was an increase in rVAS two days after discontinuation of PCA because of patient discharge from hospital (P = 0.50). There was an increase in sVAS two days after discontinuation of PCA because of patient discharge from hospital but we could not determine whether there was a trend to decreased sVAS over time within the first 8 days postoperatively (P = 0.11) (P = 0.34)  . The res< 0.001) . In the hospital . Through = 0.11) . The ove = 0.34) . Drowsin = 0.34) .The present study was designed to evaluate the effects of pregabalin on postoperative tonsillectomy pain control and to control for the influence of sedation or dizziness. In this study, we have demonstrated that pregabalin reduced the fentanyl requirement significantly in the pregabalin group compared with the diazepam control group. Pain scores both at rest and during swallowing in the pregabalin group following tonsillectomy were lower than in the diazepam group, although a significant difference was not found. To our knowledge, this is the first study that has investigated the effectiveness of pregabalin premedication on postoperative tonsillectomy pain control compared with diazepam as an active placebo.P < 0.001), which is concordant with the findings of other studies [Pregabalin was originally developed as a spasmolytic agent and adjunct for the management of generalized or partial epileptic seizures resistant to conventional therapies . The pha studies –9,13 thaP > 0.05, The postoperative side effects that accompanied the surgery when pregabalin was used as a preemptive analgesic conflict with previous results. In a consecutive report regarding laparoscopic OB/GYN surgery by Jokela et al. ,16, the The dosage and medication method of pregabalin that effectively reduce postoperative pain and minimize the adverse effects have not yet been delineated. In a study by Mathiesen et al. , patientTo investigate purely pain control while reducing the influence of side effects such as sedation, we used diazepam as an active control. However, this study has some limitations. The measures of pain may be influenced by the patient’s compliance or subjectivity. Therefore, further studies using neurotransmitters ,12, suchAlthough opioids play a fundamental role in the management of post-tonsillectomy pain, their use is associated with a number of side effects, including nausea, vomiting, and respiratory depression. Therefore, it is necessary to develop an effective approach to control post-tonsillectomy pain by combining treatment modalities that can block different pain mechanisms. In our study, pregabalin, which can control central neuronal pain sensitization, decreases fentanyl consumption without increasing the incidence of adverse effects compared with diazepam, which has a sedative effect. We believe that these results indicate that although pregabalin may have sedative side effects, in the context of post-tonsillectomy pain it has a more analgesic effect than a sedative effect. Therefore, we suggest that the addition of pregabalin prior to tonsillectomy may play an adjunct role in the control of post-tonsillectomy pain.The administration of 300 mg pregabalin prior to tonsillectomy decreases fentanyl consumption without increasing the incidence of adverse effects compared with 4 mg diazepam.S1 CONSORT Checklist(DOC)Click here for additional data file.S1 Protocol(DOCX)Click here for additional data file.S2 Protocol(DOCX)Click here for additional data file.


Microvascular decompression (MVD) of the trigeminal nerve has been so far reported to be effective in 12/19 SUNCT and SUNA patients (63 %) with neurovascular compression.We report the outcome of MVD, using Jannetta procedure, in nine cases of medically intractable chronic SUNCT and SUNA patients.Nine patients with chronic SUNCT and SUNA with a vascular loop indenting or distorting the trigeminal nerve ipsilaterally to the side of the pain demonstrable on MRI scan were offered MVD of the trigeminal nerve. All the patients failed to respond or tolerate adequate dosages of: lamotrigine, topiramate, oxcarbazepine, carbamazepine, duloxetine, pregabalin or gabapentin and greater occipital nerve blocks. Intravenous lidocaine improved the pain only during infusion in some of them.Seven SUNCT and two SUNA patients underwent MVD of the trigeminal nerve. They all had multiple daily severe headache attacks at baseline. At a median follow-up of 15 months (range: 8-30 months) after the operation, four patients became and remained pain free, one patient each had 90%, 70% and 50% improvement, respectively. The patient who improved by 50% was rendered pain free on preventive treatments. Two patients became pain free for 12 months, before pain returned. One patient suffered a CSF leak after the procedure.MVD of the trigeminal nerve was effective in 7/9 SUNCT/SUNA patients (78%). Although longer follow-up is needed to establish the long term outcome of this procedure, these preliminary data support the role of MVD in the surgical management of SUNCT and SUNA.No conflict of interest.