Pain following surgical removal of impacted molars has remained an important concern among practitioners. Various protocols have been proposed to reduce postoperative pain. However, each one has special side effects and limitations. As green tea possesses anti-inflammatory and antibacterial properties, the aim of the current study was to evaluate the effectiveness of green tea mouthwash in controlling postoperative pain.In a study with split-mouth and double blind design, 44 patients in need of bilateral removal of impacted third molars underwent randomized surgical extraction; following one surgery patients rinsed with a green tea mouthwash from the first to seventh postoperative day and after other extraction rinsed with placebo mouthwash in the same duration. Both patients and surgeon were blinded to the type of mouthwash. The predictor variable was type of mouthwash and primary outcome variable was postoperative pain measured by visual analogue scale (VAS) during first week after surgery. In addition, number of analgesics patients used after surgery recorded. To measure the effect of green tea mouthwash, repeated measures test with confidence interval of 95% was performed.Total of 43 patients with mean age of 24 years underwent total of 86 surgeries. VAS value had no statistically difference prior rinsing among groups . However, the mean value of VAS following rinsing with green tea was statistically lower than placebo in postoperative days of 3–7 . In addition, while rinsing with green tea, patients took significantly lower number of analgesics after surgery . No side effects reported.Green tea mouthwash could be an appropriate and safe choice to control postoperative pain after third molar surgery. The main aim of dental practices is not only to provide appropriate treatment and restore function, but also is to remove pain and bring relief the to their patients . On the Various medications have been used to control postoperative pain following surgical removal of impacted molar teeth ,7-13. AnGreen tea (Camellia Sinensis) has been a popular drink in eastern countries for many years. Green tea is very rich in polyphenols including catechins which possess antioxidant, antidiabetic, antimutagenic, antiviral, antibacterial, and anti-inflammatory properties . It has The purpose of this study was to address the following question: is green tea mouthwash effective in relieving the pain following surgical removal of impacted mandibular third molars? The investigators hypothesized that the pain following rinsing with green tea after surgical removal of mandibular impacted third molar would equal to the pain following rinsing with placebo mouthwash.This study was performed at Mashhad Oral and Maxillofacial Surgery Clinic. The Ethical Committee of Mashhad University of Medical Sciences approved the study protocol and all the patients provided a signed detailed informed consent.To investigate the research hypothesis, the investigators performed a split-mouth, randomized, double-blind study based on the consent statement and Declaration of Helsinki.The study population consisted of 44 patients in need of bilateral impacted third molar surgery between April 2012 and September 2012.The inclusion criteria were: be 18–30 years old; have bilateral mandibular impacted third molars; have moderate difficulty level of impacted teeth on both sides of mandible based on the sum score of values regarding the spatial direction of the teeth, depth of impaction, and relationship with the ramus on preoperative panoramic radiography . The outcome variable was self-reported pain (based on VAS). Other study variables were demographic variables (including age and sex), surgical variables (including operation time and extraction difficulty score), and post surgical variables . Operation time defined as time between the first incision till flap closure.Green tea extract prepared in the pharmacology laboratory of Mashhad University of Medical Sciences with the following protocol: Camellia Sinesis leaves were dried in 40°C for 45 minutes and powdered with electrical mortar; 100 grams of powder mixed with 500 ml of water; After 48 hours this mixture was filtered and the sediment was removed; The remnant solution was stored in room temperature; After 4 days the powder of green tea extract was obtained.To obtain the green tea mouthwash, 5 g of extracted solved in 100 ml distilled water to produce 5% mouthwash. The rinse poured into 250 ml dark bottles. The placebo mouthwash consisted 250 ml distilled water. In addition, the mint flavor added to both study and placebo rinses to make the rinse type unidentifiable for patients.All the surgeries performed by an experienced surgeon using the same protocol: povidone iodine solution was applied around the mouth; 2% lidocaine + 1:80,000 epinephrine carpules were used to block the inferior alveolar/long buccal nerves; a mucoperiosteal envelop flap was created using a standard incision; if needed, bone removal, tooth sectioning, and bone recontouring were performed with a low-speed handpiece under sufficient sterile solution irrigation; following tooth removal the socket was irrigated with 60 ml of saline; the flap was sutured using 3–0 silk sutures. Patients were instructed to take two pills of Acetaminophen (325 mg) one prior the surgery and another 4 h after surgery. From the next day, patients instructed to take analgesics (Acetaminophen) after VAS assessment and also to record time and number of analgesics they had taken.Following each surgery, patients received a bottle containing 250 ml mouthwash. Each patient received both green tea extract and placebo mouthwash during study period; however, the type of rinse received for the first surgery was selected by flip of a coin. Randomization of surgical side in each patient was kept unknown to surgeon and patients till the end of the study period.Patients were instructed to rinse with 15 ml of mouthwash two times per day from one day after surgery till seven consecutive days. To record the pain, patients were instructed to quantify the level of their pain by using a 100 mm ruler as the visual analogue scale (VAS); 0 was no pain and 100 was severe and unbearable pain. Each VAS was recorded at the morning of 7 consecutive postoperative days before taking any analgesic medication and prior to rinsing.Two follow-up appointments, two days and 7 days after surgery, were held after each surgery to evaluate the healing process. In addition, the patients were told to come back if they faced persistent or increasing pain.Appropriate descriptive statistics  computed for each variable. To analyze data, Chi-square, independent sample t-test, and repeated measures of ANOVA were performed using SPSS software version 11.5 with the confidence interval of 95%.Total of 44 patients met the inclusion criteria; however, one patient excluded as he did not participate second surgery during study period. The mean age of participants was 23.67 ± 4.78. There were no significant differences in age, gender, surgical difficulty, and operation time in both groups . There were also significant changes in VAS values during the first week in both groups . Between groups analysis revealed that in study group the mean value of VAS was significantly lower in days 3 to 7 in comparison to control group . Also significant changes observed in number of analgesics during 7 postoperative days when considering grouping . Moreover, the number of analgesics used in green tea group was significantly lower than the control group in days 1–5 after surgery Table . Most ofNo side effects following rinsing with green tea or placebo mouthwashes reported.The aim of this study was to evaluate the effectiveness of green tea mouthwash on postoperative pain of impacted third molar surgery. The study hypothesis was rejected as the pain experienced by patients was significantly lower in study group when compared to control group.Pain following surgical removal of impacted molars is a common complication which starts few hours after surgery as the effect of local anesthesia has eliminated. To relief this pain, various protocols have been proposed; none of which was based on herbal medicine -13,21-29The mechanism of postoperative pain has dedicated to trauma during surgery as it increases biochemical mediators of pain and inflammation including prostaglandins, histamine, bradykinine, and serotonin . These mAromatic components of green tea have shown anti-inflammatory properties at the site of inflammation ,32. ResuIn addition to inflammation, bacterial infection following impacted molar surgery increases postoperative pain ,25. CateThe effectiveness of green tea mouthwash was in consistent with studies using antibiotics, chlorhexidine mouthwash, or low level laser therapy (LLLT) which have shown significant reduction in postoperative complications including pain ,24-29. HThis study was double blind as either the surgeon or the patient had no idea about rinsing solution. In addition, as the study was split-mouth, each patient served as his/her own control. This design led to elimination of age and gender as confounding variables. We also controlled for other confounding factors including difficulty of surgery, operation time, surgeon experience, and number of analgesics used after surgery.Previous reports state that amount of trauma during surgery affect the magnitude of postoperative pain directly ,33. Two According to the results of this study, number of patients used analgesics and also number of analgesics taken, were lesser in study group in comparison to control group. This could be dedicated to effectiveness of green tea in controlling postoperative pain. In addition, as the greater proportion of analgesics was taken during first two days after surgery and control group used higher number of analgesics, the insignificant difference in VAS of second day in two study groups may be related to analgesic drugs.Pain has a subjective nature and there exists difficulties to measure it. Seymour et al. reported that visual analogue scale (VAS) is a sensitive and reliable tool to evaluate the pain following surgical extraction of impacted molars . This scThere were also some limitations in the current study. Rinsing with mouthwash during the day of surgery lead to blood clot resolution; hence, we had to prescribe analgesics at the day of surgery – as the postoperative pain reaches highest level 6–12 h after surgery – and instruct patients to start rinsing at the first postoperative day. This limitation is under research as investigators have designed a study to use green tea extract via slow releasing systems that is usable immediately after surgery.The results of the current study indicated that daily rinsing with green tea may be beneficial to control postoperative complications of impacted molar surgery including pain. Moreover, the need for analgesics would become less and side effects following using antibiotics, NSAIDs, or chlorhexidine mouthwash could be escaped.The authors declare that they have no competing interests.ME and AN designed the study and wrote the study protocol. ME performed surgeries. NMR provided VAS and collected demographic and surgical data. AN performed randomization and kept it secret. HM analyzed the data and performed literature review. All authors participated in drafting, critical evaluation, and approval of final version of manuscript. All authors read and approved the final manuscript.


Objective: To study various characteristics of chest pain in acute myocardial infarction patients.Methodology: A total of 331 patients of AMI admitted at Cardiology unit Nishtar Hospital Multan and Chaudhry Pervez Elahi Institute of Cardiology Multan, irrespective of the age and gender, were included in this study. The study duration was one year starting from June 2011 to June 2012. Non-probability purposive sampling technique was used in this descriptive study. Informed consent to participate in this study was taken. Data were entered and analyzed using SPSS-11.Results: A total number of 331 patients with AMI were included in the study. Mean age was 54.99±11.25 years with minimum age 20 years and maximum age 90 years. It included 264(79.8%) male and 67(20.2%) female patients with male to female ratio of 3.9:1. Out of these 331 patients 308 (93.1%) patients reported chest pain as the presenting complaint. Remaining 23(6.9%) presented with clinical features other than chest pain. There were 127(38.4%) patients with pre-cordial chest pain, 115(34.7%) had retrosternal chest pain, 58(17.5%) were having epigastric pain. Severe chest pain was seen in 281(84.9%) patients while 26(7.9%) had only mild chest discomfort. Radiation of the pain to shoulder, neck and jaw was seen in 75 (22.7%) patients. In 42(12.7%) patients, pain radiated to both sides of chest. Another 55(16.6%) patients had pain radiation to chest, shoulder, upper arm and ulnar side of left forearm. Chest pain radiation to interscapular region along with both sides of chest was present in 10(3.0%) patients. In 11(3.3%) patients’ pain radiated only to left side of chest. Pain persisting for >20 minutes was reported by 298 (90%) patients while only 10(3.1%) had pain persisting for <20 minutes. Conclusion: There is considerable overlap in chest pain of cardiac as well as non cardiac causes. However, vigilant evaluation of characteristics of chest pain in history taking may help to overcome this dilemma. Severe and prolonged precordial chest pain in a male patient between the age of 41-70 years, with pain radiation to left shoulder, neck and jaw is highly suggestive of AMI. The clinical diagnosis of AMI requires an integrated assessment of the history especially with reference to chest pain along with some combination of indirect evidences of myocardial infarction using biochemical, electrocardiographic, and imaging modalities. In the United States, nearly one million patients suffer from AMI per year.Chest pain is the most common presenting complaint of acute myocardial infarction. The classic manifestation of ischemia is usually described as a heavy chest pressure or squeezing, a “burning” feeling, or difficulty in breathing. The discomfort or pain often radiates to the left shoulder, neck, or arm. Chest pain may be atypical in few cases. It builds in intensity over a period of few minutes. The pain may begin with exercise or psychological stress, but acute myocardial infarction most commonly occurs without obvious precipitating events.3 However, diagnostic evaluation reveals that only 15 to 25 percent of patients with acute chest pain actually have acute coronary syndrome.4,5 The difficulty is to discriminate patients with acute coronary syndrome from those with non-cardiac chest pain. Pope et al found that only 2.1 percent of patients with chest pain having acute myocardial infarction were discharged from the emergency department.6 Patients with acute myocardial infarction who are mistakenly discharged from the emergency department have short-term mortality rates of about 25 percent, at least twice what would be expected if they were admitted.7Each year five million patients come to emergency departments with chest pain.It is therefore of utmost importance to emphasize the evaluation of chest pain and to discriminate chest pain of acute myocardial infarction from non-cardiac chest pain. By doing this, we can eliminate the chances of mistaken discharge of patients with acute myocardial infarction having initial normal ECG. We can also decrease undue burden on health personnel by avoiding mistaken admission of those patients who do not actually have myocardial infarction or acute coronary syndrome.So the present study was conducted to find out the characteristic and peculiar features of chest pain which can ultimately help in diagnosis of AMI.A total of 331 patients of AMI admitted at Cardiology unit Nishtar Hospital Multan and Chaudhry Pervez Elahi Institute of Cardiology Multan, irrespective of the age and gender, were included in this study. The study duration was one year starting from June 2011 to June 2012. Non-probability purposive sampling technique was used in this descriptive study. Informed consent to participate in this study was taken. A pre-designed questionnaire was used to record the data. Data were entered and analyzed using SPSS-11.A total number of 331 patients with AMI were included in the study. Mean age was 54.99±11.25 years with minimum age 20 years and maximum age 90 years. It included 264(79.8%) male and 67(20.2%) female patients with male to female ratio of 3.9:1. Out of these 331 patients 308 (93.1%) patients reported chest pain as the presenting complaint. Remaining 23(6.9%) presented with clinical features other than chest pain.Majority of the patients i.e. 278(83.98%) were between the age of 41-70 years. There were 22 (6.64%) patients between the age of 71-90 years. Only 5(1.51%) were 30 years and below. There were 127(38.4%) patients with pre-cordial chest pain, 115(34.7%) had retrosternal chest pain, 58(17.5%) were having epigastric pain and only 2(0.6%) had pain in the back of chest as initial symptom. Only 3 (0.9%) patients had pain both in epigastrium and retrosternum. Severe chest pain was seen in 281(84.9%) patients while 26(7.9%) had only mild chest discomfort.Radiation of the pain to shoulder, neck and jaw was seen in 75 (22.7%) patients. In 42(12.7%) patients pain radiated to both sides of chest. Another 55(16.6%) patients had pain radiation to chest, shoulder, upper arm and ulnar side of left forearm. Chest pain radiation to interscapular region along with both sides of chest was present in 10(3.0%) patients. In 11(3.3%) patients’ pain radiated only to left side of chest. Another 11(3.3%) had pain radiation to ulnar side of arm only. Radiation of pain to the left shoulder alone was present in 16(4.8%), to interscapular region alone in 9 (2.7%) and to jaw alone in 4(1.2%) patients and 68 (20.5%) did not describe radiation to any site.Pain persisting for >20 minutes was reported by 298 (90%) patients while only 10(3.1%) had pain persisting for <20 minutes. Ninety two (27.8%) patients had sensation of heavy weight over chest. Pain was constricting in 36 (10.6%), choking in 30(9.6%), burning in 48 (14.5%) and stab like in 42 (12.7%) patients. Only 2(0.6%) had reported both choking and constricting pain while, another 2(0.6%) had choking as well as burning character chest pain. Acute myocardial infarction occurred in morning time in 128(38.7%) patients, 98 (29.6%) patients had AMI in evening while in 96(29.0 %) AMI occurred at night and 9 (2.7%) patients could not clearly describe the timing of onset.8-10Despite of all advances in the management of cardiovascular diseases, yet discrimination between chest pain due to AMI and non- cardiac chest pain remains a dilemma. Unfortunately, not much literature is available about the characteristics of chest pain to differentiate these two conditions. Only three of the selected studies combined different signs and symptoms for the diagnosis of AMI.11 In our study, we found that majority of the patients were between the age of 41-70 years, while a study conducted by Malik et al, 85% of the patients were between 41-60 years of the age.2 Age of presentation was slightly higher in our population as compared to that which was noticed by British Heart Foundation i.e. 30-69 years.12 In Belgium Bartholomeeussen et al13 found that incidence of AMI is high at the ages between 45–75 years. Our results are in accordance with the study conducted by Bartholomeeussen et al.13 However the mean age for first MI among south Asian is lower compared to the individuals in other countries.14Age is an important determinant of AMI in patients having chest pain. Incidence of AMI increases with increasing age. In females age of presentation is even higher by 5-10 years.15 Risk factors like hypertension and hyperlipidemia are more prominent for men than women in the late 40- to early 50-year range; then their prevalence is higher in women. Women have an extra protection during their early reproductive life due to the effect of sex hormones. In our study majority of the patients with AMI were male (79.8%). Studies conducted by Hafeez et al and Shabbir et al also showed male dominance.16,17 Albarran et al18 had also discovered that AMI is more common in males (68%) as compared to females (32%). Chirsten et al19 found AMI prevalence was 62% in males. In a local study conducted by Mujtaba et al20 at Karachi had also similar findings.At any given age, prevalence of coronary heart disease is greater in men than in women.21 Bosner et al22 analysed 1212 patients (534 men and 678 women) for the aetiology of their chest pain; of those 180 patients (92 men and 88 women) were diagnosed as having CHD. Pain was present on the left side of chest in 56 (63.6%) females and in 63 (68.5%) males. Bosner et al22 noticed that chest pain was localized on the right side of the chest in 34.1% patients. However, in our settings none of the patient presented with right sided chest pain.Site of the chest pain gives important clue to the diagnosis of ACS/AMI. Pain which is located in the center of chest is more likely to be ischemic than a peripherally located chest pain. We found that precordial chest pain is the most common site for chest pain. There were 127(38.4%) patients with precordial chest pain in our setting. De Silva also noticed that precordial and retrosternal sites are most common sites for chest pain in CAD.23,24 This is because of presence of heart on the left of chest, so pain radiates along left sided cervical nerve roots. In our study 55(16.6%) patients had pain radiation to left shoulder, left upper arm and ulnar side of left forearm. Solt et al25 claimed a high prevalence of chest pain radiation to the jaw especially in females. However, we have noticed that only 4(1.2%) patients had pain radiation to the jaw alone but pain radiation to the jaw was present in combination with radiation to shoulder and neck in 22.7% patients.Most common site where AMI pain radiates is left shoulder and arm.26,27 However those attacks of chest pain that are not very severe or prolonged, but distressing enough for patients to contact a general practitioner, present a more difficult problem in diagnosis and management.28Duration of chest pain more than 20 minutes can be taken as cutoff for AMI. In our study, it was found that 90% of patients had chest pain persisting for >20 minutes. Similar results have been proven in multiple other international studies.16 Abidov et al29 also found that some patients may present with symptoms other than chest discomfort; such as “angina equivalent” symptoms include dyspnea (most common), nausea and vomiting, diaphoresis, and unexplained fatigue. Chest pain remains most important symptom of AMI but in few patients it may not be there. Further studies on large scale are required about the characteristics of chest pain favoring AMI.Although chest pain is the most important symptom of AMI but it may be invariably absent in some patients. In our setting 6.9% patients had symptoms other than chest pain (painless AMI). In a study conducted by Hafeez et al pain less MI was seen in 6 % of the patients.There is considerable overlap in chest pain of cardiac as well as non cardiac causes. However, vigilant evaluation of parameters of chest pain in history taking may help to overcome this dilemma. Severe and prolonged precordial chest pain in a male patient between the age of 41-70 years, with pain radiation to left shoulder, neck and jaw is highly suggestive of AMI.


Under-diagnosis of pain is a serious problem in cancer care. Accurate pain assessment by physicians may form the basis of effective care. The aim of this study is to examine the association between late referral to a Palliative Care Team (PCT) after admission and the under-diagnosis of pain by primary physicians.by the palliative care physicians only. Late referral to PCTs after admission was defined as a referral to the PCT at ≥20 days after admission. Because the two groups displayed significantly different regarding the distributions of the duration from admission to referral to PCTs, we used 20 days as the cut-off point for “late referral.”This retrospective study was performed in the Teikyo University teaching-hospital for a period of 20 months. We investigated triads composed of 213 adult cancer inpatients who had coexisting moderate or severe pain at the initial PCT consultation, 77 primary physicians, and 4 palliative care physicians. The outcome of the present study was the under-diagnosis of pain by primary physicians with routinely self-completed standard format checklists. The checklists included coexisting pain documented independently by primary and palliative care physicians at the time of the initial PCT consultation. Under-diagnosis of pain was defined as existing pain diagnosed p < 0.0001). After adjusting for potential confounding factors, under-diagnosis of pain by the primary physicians was significantly associated with late (20 or more days) referral to a PCT . Other factors significantly associated with under-diagnosis of pain were coexisting delirium and case management by physicians with < 6 years of clinical experience.Accurate pain assessment was observed in 192 triads, whereas 21 triads displayed under-diagnosis of pain by primary physicians. Under-diagnosis of pain by primary physicians was associated with a longer duration between admission and initial PCT consultation, compared with accurate pain assessment (25 days versus 4 days, Under-diagnosis of pain by primary physicians was associated with late referral to PCTs. Shortening the duration from admission to referral to PCTs, and increasing physicians’ awareness of palliative care may improve pain management for cancer patients. It is commonly believed that 75% of patients with cancer will have pain at some point in their disease process and that adequate pain management can be achieved through simple measures in 85 − 95% of cases ,2. HowevIt has been reported that accurate pain assessment by physicians is associated with improved outcomes for pain management -8. In adIn previous studies, the barriers to pain assessment have been examined from a variety of perspectives, including barriers related to patients and health care professionals . The mosThe aim of the present study was to assess the relationship between late referral to a PCT after hospital admission and the under-diagnosis of pain by primary physicians in Japan, which may help to identify the optimal time to consult with a PCT for pain assessment.We retrospectively examined the relationship between the duration from admission to initial PCT consultation and under-diagnosis of pain by primary physicians. We reviewed the electronic medical records of 351 consecutive cancer inpatients who had been referred to the PCT between June 2009 and March 2011. Our study samples comprised triads of patients and their primary and palliative care physicians at the initial PCT consultation.The present study was conducted according to the principles of the Declaration of Helsinki. The study protocol was reviewed and approved by the Institutional Review Board and the Ethics Committees of Teikyo University.We conducted this study at Teikyo University Hospital, in Japan, which is a teaching-hospital with 24 medical departments and 1154 beds, providing general acute care. The Department of Palliative Care at the hospital has provided PCT services since April 2009.We retrieved data from all consecut ive cancer inpatients over 18 years of age and with moderate to severe pain who were referred to the PCT of the hospital by their primary physicians during a 20-month period. Patients who were referred to the PCT on two or more occasions, and those without moderate or severe pain were beyond the scope of this study and were excluded from the study. We defined coexisting moderate or severe pain as that rated by patients at an intensity of pain was either ≥ 4 on the Numerical Rating Scale (NRS), or ≥ 8 on the Abbey Pain Scale (APS), documented by palliative care physicians ,16.All primary physicians  who referred a selected patient to the PCT were included in the study.The PCT comprised three palliative care physicians, one psycho-oncology physician, and two nurse practitioners. The service provided by the PCT was primarily consultative and was available to all inpatients upon request by a patient’s primary physician. The PCT conducted daily rounds and participated in decision-making for the treatment program, critical care, nursing, respiratory therapy, and nutritional service. At the initial PCT consultation, the palliative care physicians assessed the referred patients, proposed problems, and organized possible solutions.Primary and palliative care physicians independently recorded each patient’s problems using the same standardized checklist  at the initial PCT consultation. As cancer pain is generally chronic, and given that the mean interval between referral to the PCT and the initial medical interview by the PCT was 0.7 days, we considered the assessment of cancer pain by primary and palliative care physicians to have been performed at the same time. In addition, primary physicians documented the reason for referral to a PCT, and the intensity and locations of pain were documented by primary physician. The form for palliative care physicians comprised three parts; patients’ checklists documented by palliative care physicians, characteristics of pain rated by patients, and assessment and therapy plan documented by palliative care physicians. The characteristics of pain, such as a diagram of locations of pain, and intensity of pain as measured in the patient’s marks on the NRS, were based on the Brief Pain Inventory (BPI) . For patTo directly compare the assessments of primary and palliative care physicians, we defined accurate pain assessment as the identification of existing pain by both primary and palliative care physicians using the standard format at the time of the initial PCT consultation. Under-diagnosis of pain was defined as the identification of pain by only palliative care physicians.Various definitions of “palliative care consultation” or “referral” have been proposed ,18. The Covariates that can affect pain assessment by a physician include patient demographics, such as age (continuous), gender, primary cancer site, Karnofsy Performance Status (KPS), therapy status, purpose of admission, current opioid use at the initial PCT consultation, duration of hospitalization, coexistence of delirium, as well as physician characteristics, such as years of experience , and clinical department. Current opioid use at the initial PCT consultation has been shown to affect the prescription of opioids by a primary physician and to reflect a physician’s knowledge of palliative care .From 2003 to 2006, the Cancer Control Act was established to improve the quality of life for all cancer patients in Japan, and disseminating the knowledge of palliative care among physicians was identified as an important area of improvement. Since the Act took effect, palliative care has been a part of medical education, and so physicians with 6–10 years of experience have studied palliative care as medical students. Therefore, we used this group of physicians as a reference. The coexistence of delirium was diagnosed by a psycho-oncology specialist, who was a member of the PCT, using the Diagnostic and Statistical Manual of Mental Disorders (DSM-IV) criteria. Clinical departments were divided into three categories based on clinical experience related to cancer patients, as collected from the database of cancer patients registered at the hospital in 2009. As the physicians’ gender was not reported with regard to barriers to pain assessment, it was excluded from the covariates.First, we summarized the baseline demographics of the patients and physicians, and the symptom profiles, including percentages and medians for clinical variables. Second, the results of the baseline assessment were compared according to the two categories of pain assessment: accurate pain assessment and under-diagnosis of pain by primary physicians. Comparisons were made using the Wilcoxon rank-sum test for continuous variables and the chi-square test or Fisher’s exact test for categorical variables, depending on the variable type and data distribution.P < 0.05 (two-sided) were considered to indicate statistical significance. All analyses were performed using SAS software .Third, logistic regression models were used to assess the relationship between late referral to the PCT and the risk for under-diagnosis of pain after adjusting for covariates. The results were shown as the odds ratio (OR) and 95% confidence interval (CI). No multicollinearity was observed among the independent variables. Values of Of the 351 hospitalized patients consecutively referred to a PCT during the study period, 69 were excluded because they had been referred to the PCT on two or more occasions, and another 69 patients were excluded because they did not have moderate or severe pain . The majority of the primary physicians (81%) were male and 40% had been practicing medicine for 6–10 years. The primary physicians had consulted with the PCT 3.7 ± 0.6 times (mean and standard deviation).Table The majority of patients (91%) were referred to the PCT for advice regarding symptom management. The rate of diagnosis of pain by both primary and palliative care physicians was 66%. These findings were nearly the same as those of previous studies .p < 0.0001). Physicians with clinical cancer experience used the NRS to assess the pain intensity. Neither clinical departments (Tables The relationships between triads characteristics and pain assessment by primary physicians are shown in Table s Tables  and 4 noWe performed a multiple logistic regression analysis for the effect of late referral to the PCT on under-diagnosis of pain. After adjusting for patient age, gender, KPS, primary cancer site, treatment status, purpose of admission, coexistence of delirium, duration of hospitalization, current opioid use at the initial PCT consultation, primary physician clinical department, and primary physician experience, the analysis revealed that late referral to the PCT was significantly associated with an under-diagnosis of pain (OR, 2.91; 95% CI, 1.27 − 6.71; Table The main finding of the prese nt study was that under-diagnosis of pain by primary physicians was associated with a long duration between admission and the initial PCT consultation. Patients who were referred to the PCT more than 20 days after admission were 2.91 times more likely to have experienced under-diagnosed pain by primary physicians than those referred earlier. This association was independent of age, gender, KPS, primary cancer site, treatment status, purpose of admission, coexistence of delirium, current opioid use, duration of hospitalization, clinical department, and years of experience of the primary physician. To our knowledge, few studies have demonstrated a relationship between late referral to the PCT and under-diagnosis of pain. These results support previous studies that showed early referral to palliative care was related to improved quality of care .The World Health Organization defines palliative care as “an approach that improves the quality of life of patients and their families facing problems associated with life-threatening illnesses,” and states that this is achieved “through the prevention and relief of suffering by means of early identification and impeccable assessment and treatment” . AlthougIn the present study, late referral to a PCT was associated with the under-diagnosis of pain by primary physicians, and thus a long duration of hospitalization preceded the late referral to a PCT. As patients with advanced cancer deteriorate over time, they may develop a state of unconsciousness, such as delirium. Delirium and psychological problems may contribute to the under-diagnosis of pain. We found that delirium was more common in patients with later referrals to the PCT than in those who received early referrals, and that patients with no delirium were significantly associated with the under-diagnosis of pain (OR 2.92, 95% CI 1.23 − 6.94; Table However, we considered the possibility that the under-diagnosis of pain would lead to late referral to the PCT. Previous studies have investigated patient’s and physician’s factors related to the under-diagnosis of pain -12. The Previous studies have reported that early referral to PCTs is beneficial to cancer patients, however, physicians usually refer patients to specialized palliative care programs in the very late stages of cancer ,18. AlthThe present study has several limitations. First, this study was conducted at a single institution using a retrospective design. Nevertheless, we believe our findings can be generalized to numerous hospitals and physicians. Although our study included a homogenous study population, a low exclusion rate, and an adjustment for important confounders, the nature and number of problems documented at the initial PCT consultation did not differ from those reported in previous studies . FurtherMoreover, we did not directly measure the physicians’ knowledge of palliative care which is considered a factor in the under-diagnosis of pain. However, physicians who had been practicing for 6–10 years, and thus had been trained in palliative care after 2003, tended to refer patients to the PCT sooner and generally displayed greater knowledge of palliative care. Thus, a physician’s years of experience served as a surrogate for knowledge of palliative care in the present study.Finally, we did not consider the strength and type of pain experienced by patients. The effects of these variables on accurate pain assessment should be prospectively evaluated in a future study.Despite these limitations, this study presents findings with important implications and suggests the benefits of early referral to a PCT, as a long duration between admission and initial PCT consultation was associated with under-diagnosis of pain of cancer inpatients. These findings emphasize the need for earlier referral to PCTs for accurate pain assessment for primary physicians.The authors declare that they have no competing interests.MA, EY, and EA designed the study and drafted the paper. MA led the data collection and analysis. MA wrote the paper. All authors contributed to the paper, reviewed drafts and approved the final content. All authors read and approved the final manuscript.The pre-publication history for this paper can be accessed here:http://www.biomedcentral.com/1472-684X/11/7/prepub


Hip fractures account for 350,000 fractures annually and the projected incidence is expected to exceed 6.3 million by 2050. As the number of hip fractures continues to increase as a result of the aging American population, the importance of limiting and preventing complications is magnified.This study demonstrated the clinical effects of a continuous fascia iliaca compartment block placed pre-operatively when combined with a comprehensive pain protocol. All patients who presented to our institution with a hip fracture were given the option of having a continuous fascia iliaca compartment block for pain control versus usual pain management . The block was monitored by the pain service until the day of discharge from the hospital. Data was collected regarding mean pain scores, average length of stay and opioid medication use.There were eighteen males and twenty four females. The pain score on post-operative day zero was reduced from a 2010 annual average of 4.1 to 1.7 in the pilot study group on the visual analog score. On post-operative day one, the 2010 annual average was 2.9 compared to 1.4 in the pilot study group. The length of stay was decreased from the 2010 annual average of 5.9 days to 4.8 days in the pilot study group. The patients used an average of 18mg of morphine equivalent medications during the average infusion time of 40.7 hours. There were no falls or infections noted within our pilot study group.Overall, it has been noticed that the reduction in opioid usage in this elderly patient population, with an average age of seventy five years, has produced alert and mobile patients often as early as post-operative day one. The length of stay has decreased along with the average pain score in the pilot sample of forty two patients.Hip fracture; Fascia Iliaca Compartment Block; Pain Score Hip fractures account for 350,000 fractures annually and the projected incidence is expected to exceed 6.3 million by 2050 . As the Multiple studies support this finding stating that fascia iliaca compartment blocks following hip fractures are effective and easily learned . Fascia It has been shown that patients with higher post-operative pain have an increased length of hospital stay, delayed ambulation, and long-term functional impairment .Summarily, the concerns regarding patients with hip fractures include pre-operative pain control, side effects from systemic medications, post-operative pain control, and complications including falls. It appears from the literature that the implementation of a fascia iliaca compartment block protocol could reduce the occurrence rate of all the identified concerns.This study was approved by the IRB at Miami Valley Hospital .During January 2011, forty two patients were identified either as a transfer from another facility or upon presentation to the emergency department with a hip fracture. Following identification, each patient was given the option of having a continuous fascia iliaca compartment block (FICB) for pain control. All patients were included for this protocol; there were no exclusion criteria except for patient consent for participation. The anesthesiologist was contacted and consent for the procedure was obtained. The majority of the blocks were done in the emergency department with a minority being done on the orthopaedic unit for patients transferred from other hospitals. The block was performed anywhere from 1 - 4 hours after arrival to the hospital. The fascia iliaca is located anterior to the iliacus muscle within the pelvis. It is joined superior-laterally to the iliac crest and medially to fascia overlying the psoas muscle. Using ultrasound to locate the fascia layer of the psoas muscle, a needle was injected through the skin proceeding just underneath the fascia. Ultrasound permits the visualization of the needle tip piercing the fascia lata then the iliacus fascia. Local anesthetic was then injected which creates a fluid-filled space beneath the fascia. The local anesthetic travels cephalad and reaches the nerves of the lumbar plexus: the femoral, the lateral cutaneous and the obturator. This procedure is a compartment block, therefore 50 - 60 ml of local anesthetic is injected. For longer lasting analgesia, a catheter was threaded through the needle into the fascia iliaca area. A continuous infusion of local anesthetic is then joined to the catheter and maintained for several days using the On Q Pain ball. After an initial bolus of 60mL of 0.5% ropivacaine, a continuous infusion of 0.2% ropivacaine was infused at an average rate of 10mL/hr maintained until 1 - 2 days after surgery.The block effects were monitored by the perioperative pain service. During this time, a standard protocol at our institution for patients with hip fractures was implemented including the pre-emptive receipt of Celebrex and Lyrica unless contraindicated, scheduled Tylenol, and oral and intravenous opioids as needed. This protocol also includes documentation of pain scores and medication administration including opioid consumption. The data compiled from these standardized care measures was collected as part of this study. The patients are on bedrest restrictions prior to surgery due to their fracture. The pain catheter is removed on the morning following surgery and there are no restrictions as physical therapy would ensue later that day.The average age of this forty two person group was seventy five years (range 53 - 99 years). The group consisted of eighteen males and twenty four females. The mean pain score was averaged for each post-operative day from all pain scores recorded by the nursing staff for that day . The paiThe population affected by hip fractures is a population with multiple co-morbidities. There are concerns for obtaining adequate analgesia while controlling for the amount of opioid medications used. A reduction in opioid usage during hospitalization for hip fractures reduces the risk of opioid-induced side effects: acute delirium, urinary retention, and constipation. Stevens et al completed a randomized, double blind study of total hip arthroplasty patients with a modified fascia iliaca block and found a decrease in the amount of morphine used between the control and trial groups .Pain and medication use can affect the mental status of elderly patients, including the prevalence of delirium. Mouzopoulos et al found that in hip fracture patients at intermediate risk for delirium, the fascia iliaca compartment block significantly prevented the occurrence in delirium . AdequatWe demonstrated the benefits of a continuous fascia iliaca compartment block placed pre-operatively when combined with a comprehensive pain protocol as measured by pain score, opioid consumption, and hospital length of stay. Regarding future studies, we have an ongoing study comparing 200 patients with continuous infusion fascia iliaca compartment blocks with 200 patients without the blocks in our hip fracture population. We plan to do a multivariate analysis of our results in addition to a cost analysis as the hip fracture population comprises a significant amount of resources.


Introduction. Trigeminal neuropathy is most often secondary to trauma. The present study explores the underlying causes and the factors that influence recovery.Material and methods. A retrospective case study was made involving 63 patients with trigeminal neuropathy of traumatologic origin, subjected to follow-up for at least 12 months.Results. Fifty-four percent of all cases were diagnosed after mandibular third molar surgery. In 37 and 19 patients the sensory defect was located in the territory innervated by the mental and lingual nerve, respectively. Pain was reported in 57% of the cases, and particularly among the older patients. Regarding patient disability, quality of life was not affected in three cases, while mild alterations were recorded in 25 subjects and severe alterations in 8. Partial or complete recovery was observed in 25 cases after 6 months, and in 32 after one year. There were few recoveries after this period of time. Recovery proved faster in the youngest patients, who moreover were the individuals with the least pain.Conclusion. Our patients with trigeminal neuropathy recovered particularly in the first 6 months and up to one year after injury. The older patients more often suffered pain associated to the sensory defect. On the other hand, their discomfort was more intense, and the patients with most pain and the poorest clinical scores also showed a comparatively poorer course. Key words:Post-traumatic trigeminal neuropathy. Trauma, whether accidental or iatrogenic, is the most common cause of trigeminal neuropathy (TN). Most caThe present study evaluates a series of 63 patients with post-traumatic TN, with a view to identifying the underlying causes, the clinical manifestations and the factors that influence recovery.A retrospective case study was made of 63 patients seen for sensory alterations of the face and diagnosed with trigeminal neuropathy of traumatic origin in the period 1996-2009. The following inclusion criteria were established: patients showing a sensory defect in the mucocutaneous territory innervated by one or more trigeminal branches, produced by a traumatic process, and with a minimum follow-up period of 12 months. Those cases with a symptoms-free period between the time of trauma and the appearance of neuropathy were excluded. All patients gave informed consent to participate in the study.No immediate anterior traumatism capable of accounting for the neuropathy was documented. We registered the presence, degree and duration of the associated discomfort, which was rated as follows: burning, itching, stabbing, flashing pain. A clinical scale was used to score the degree of disability resulting from trigeminal neuropathy: no effect (daily life activities not affected), mild , moderate  or severe (causes important disability).Extraoral panoramic X-rays were obtained in all cases. Maxillofacial or cranial computed tomography scans were performed in some cases. Vitamin B complex was prescribed, and in the case of pain amitriptyline 50-75 mg/day and/or carbamazepine 400-600 mg/day was administered. The clinical course was assessed one, 6 and 12 months after the visit to the clinic, and at the last control, and was rated as full recovery, partial recovery, or no improvement.A descriptive analysis was made of all the study variables. Comparisons between qualitative variables were made using the chi-squared test, accepting statistical significance for p<0.05.The mean patient age was 45.4 years (range 17-76). There were 11 men and 52 women (ratio 1:5).The following antecedents of trauma were recorded: impacted lower third molar removal , simple extraction (9 patients), removal of impacted root fragments (4 patients), implant placement (9 patients), dental anesthesia in conservative dental treatment (4 patients), endodontic treatment (1 patient), and direct facial traumatisms (2 patients).In 46% of the cases neuropathy was located on the left side, in 49% on the right side, and in 5% of the cases the disorder proved bilateral. The most frequently affected territory corresponded to the third trigeminal branch: the inferior alveolar nerve in 37 cases, and the lingual nerve in 19 cases. The territory of the second trigeminal branch was affected in four cases, while the second and third branches were implicated in two subjects. Lastly, all three branches of the fifth cranial nerve were affected in one case.In addition to the sensory defect, 57% of the patients (36 cases) suffered associated pain. The pain was described as burning in 19 cases, itching in 6, stabbing in 5, and flashing or fulgurant in three. The pain was poorly defined in three patients. Regarding patient disability, quality of life was not affected in three cases, while mild alterations were recorded in 25 subjects and moderate or severe alterations in 8.In relation to drug treatment, 5 patients received no treatment, while 25 received only vitamin B complex. Combination carbamazepine and amitriptyline was prescribed in 18 patients, while four received carbamazepine alone, and 9 received amitriptyline. Lastly, two patients received other drugs and analgesics.After 6 and 12 months of follow-up, 25 and 32 patients showed improvement, respectively. On occasion of the last control (mean 3 years), 35 patients had improved. Full recovery took place in 9 cases within the first 6 months of follow-up, with another 7 cases over the next 6 months. After this period there were no further recoveries, however .Marginally significant differences were recorded on comparing the presence of pain by age intervals . Of the patients over 60 years of age, 81.3% complained of pain. In the 41-60 years age range this proportion dropped to 55%, while the youngest patients (20-40 years of age) reported pain in 44.4% of the cases. The mean age of the patients with associated pain was 50.41 years versus 38.7 years in the case of the patients without pain . A statistically significant association was observed between patient age and the presence of pain.Statistically significant differences were observed on correlating patient age to pain intensity . In effect, pain intensity was seen to increase with advancing age. This was corroborated by analysis of variance (ANOVA) between the age groups and pain intensity  – the oldest subjects reporting the greatest intensity of pain Fig. .Pain was reported by four males and 32 females, though no statistically significant differences in the presence of pain between the two sexes was observed , since many females were included in the study series. No correlations were found between patient sex and the characteristics, frequency or duration of pain.In contrast, a significant relationship was observed between pain intensity and the clinical course. This relationship was examined by mixed ANOVA, taking as independent variables the time elapsed from one clinical control to the next  and the intensity of pain , while recovery or non-recovery was taken as the dependent variable. , and as second factor the clinical score. Patient improvement in turn was taken as the dependent variable. The analysis revealed a statistically significant relationship, with lower clinical scores being correlated to greater mean patient improvement Fig. .Trigeminal neuropathy is most often secondary to trauma, with a proportion of close to 40% of all cases . The mosLikewise, due to the anatomical position of the lingual nerve in relation to the third molar, the former can be damaged during maneuvering to extract the molar ,8-10. ScTrigeminal neuropathy (TN) secondary to dental anesthesia has been little described in the literature, and was recorded in four of the cases of our series. Chan and Mulford  publisheAccording to Karas et al. , sensoryThe prognosis depends on the severity of the nerve damage. Kipp et al. , followiSandstedt and Sörensen  examined


Objective: Pain reduction has been the subject of continuous research in the field of oral and maxillofacial surgerysince postoperative pain with ranging of intensity and duration may affects the patient submitted in an oralsurgical procedure. The aim of present study was to compare the analgesic effectiveness between two differentanesthetic solutions (articaine and lidocaine) in third molar surgery.Study Design: A prospective, randomized and clinical study with patients submitted to third molar surgery at twodistinct times. The visual analogue scale, the McGill Pain Questionnaire and the analgesic consumption recordwere used to measure the pain after each surgical time.Results: Duration of surgery, latency, the amount of anesthetic used and analgesic consumption showed clinicaldifferences with highlights of articaine, though statistical significance was not observed (P<0.05). The pain scoresindicated similar anesthetic efficacy with both solutions.Conclusion: In the present study no significant differences were observed between lidocaine and articaine in thecontrol of postoperative pain. Key words: Articaine, lidocaine, pain control, lower third molar. Pain is a protection mechanism of the body to a tissue injury by different stimulations, which transmit a signal to the Central Nervous System . Dental Pain reduction has been the subject of continuous research in the field of oral and maxillofacial surgery since postoperative pain with ranging of intensity and duration may affects the patient submitted in an oral surgical procedure. Therefore, a method to decrease or eliminate patient pain has its usefulness justified . VariousThe increased availability of local anesthetics has improved interest in research about dental pain control. Nowadays the professional can select from a broad variety of local anesthetic drugs that have the specific properties demanded by the specific case of the patient and the kind of surgical procedure. The concept of local anesthetic action is based on hindering the generation and conduction of nerve impulses. Thus, the impulse is aborted, hindered from reaching the brain and is not interpreted as pain by the patient .Among the local anesthetics, lidocaine is the “standard gold” drug in nowadays. Articaine is outstanding as the local anesthetic indicated for dental procedures and control of postoperative pain ,7. The pA prospective,randomized, controlled, parallel group and comparative study design was realized with the aim of observing an association of events. This study was conducted during one year in Aracaju, Sergipe, Brazil. The studied population was selected by spontaneous or referenced demand for services from the Dentistry Department at the Federal University of Sergipe (UFS) in which each patient served as his/her own control. Participation in the study required the patient’s consent in accordance with the recommendations of the National Health Committee and Brazilian Health Department and was approved by the Research Ethics Committee of this institution by number 0025.0.107.000-06. A sample of 20 patients ranging from 18 to 30 years old was studied. The inclusion criteria were: patients undergoing removal of bilateral lower jaw third molar surgery in a symmetrical position requiring ostectomy and/or tooth sectioning for extraction. Orthopantomographic radiograms were taken to ensure the similarity of the tooth inclinations and angulations. Third molar had to be class A or B and position 1 or 2, according to Pell & Gregory classification, based on the space relationship of the tooth to the ascending ramus of the mandible and to the occlusal plane of the lower second molar. The Winter’s classification was considered for vertical and/or mesioangular position , respecting the volume of 4.5ml, with 3.6ml being injected for blocking the inferior alveolar nerve and 0.9ml reserved for blocking the buccal nerve.To perform the surgical procedure, the material and instruments routinely required for this surgery were used. The surgery to remove the lower third molar followed the standardized technique. Briefly, an “L” shaped incision was made, and a mucoperiosteal flap was elevated. When osteotomy and tooth section were performed on one side, the other side received the same treatment in order to standardize the surgical trauma. All procedures were performed under abundant irrigation with sterilized 0.9% physiological solution. The close of the mucoperiosteal flap was performed with 3-0 silk . The difficulty of the removal procedure was determined according to the 4 grades by Champbell`s method: (I) simple tooth extraction, (II) bone removal or tooth division, (III) bone removal and tooth division, and (IV) the same as (III) but very difficult , these being subdivided into 20 groups. From these, the patient only chooses a word from each group, which characterizes the current pain. After data collection, the answers were classified into the above-mentioned standards of pain. The Visual Analogue Scale ranges from 0 to 100 (0 is no pain and 100 the worst pain imaginable). The patient was instructed to draw a vertical line to designate a point on the scale to express the degree of pain intensity. According to Collins et al. . Using the principal variable, the visual analog scale (VAS) scores for postoperative pain, and considering a difference of 20 mm as clinically significant (estimated mean standard deviation 15 to 25 mm) the sample size was calculated as 20 patients in each group, that means in this study 20 patients, each side of patient with a different local anesthetic, considering a type II error of 0.20 and a type I error of 0.05, and a statistical power of 80%.Of the 24 patients entered into the study two were excluded from the analysis due to incomplete pain diary form, and the others 2 patients did not return to the second surgery. Due to the within-subject spit mouth study design with the patient constituted his/her own control, the influence of sex and weight, as well as others demographic factors, had little effect on treatment outcome.Among the studied sample of 20 patients, ranging from 18 to 30 years old, we found a mean age of 23.25 years.A prevalence of women was recorded, in a ratio of 3:1, no significant between-group differences were found in the mean duration of surgery, amount of local anesthetic used , and theIn the period of 2 hours evaluation, all patients referred pain, irrespective of the type of anesthetic used. The number of patients reported referring pain using lidocaine was the double (30%) between the levels of intense and worst, when compared with the patients who had used articaine 15%) (mean score- 26.1 mm / 29.9 mm for lidocaine), but the difference was not significant . The mean pain intensity scores throughout 24-h investigation period are shown in . The same occurred with the 6-hour period ; it should be pointed out that the worst level of pain was measured by 1 patient who used lidocaine, which did not occur when the articaine solution was used. Similar data were recorded in the 12 post-operative hours .One day after surgery, it was observed that a lower number of patients who had used articaine referred pain, and also presented slight pain intensity (4 patients). When analyzing the data obtained by the Visual Analogue Scale, the presence of pain and evaluated intensity could be determined for the type of anesthetic used, and no significant difference between the results presented for these anesthetic solutions was found.At all the evaluation times there was no quantitative difference in the number of pills who had used after surgery, considering both anesthetic solutions . The Mc Gill Pain Questionnaire generated the following measures: number of chosen descriptors and pain index. The number of chosen descriptors corresponds to the words that the sick person chooses to explain pain. The standards classified as sensory and affective were the pain evaluation descriptors which were most frequently mentioned by the patients in this study .The age of the sample consisted of patients ranging from 18 to 30 years of age, which can be verified in the majority of comparative studies related anesthetic and third molar surgery ,11,12.A gradual reduction in pain intensity was identified in the evaluated times, as well as in the percentage of patients with postoperative pain. This reduction is justified by the peaks of postoperative pain that generally occur in first 8, 12 hours ,13,14.In the present study, no difference in postoperative pain was found between the two tested anesthetic solutions. This contradicts the conclusions found in the study of Ruprecht and Knoll-Kohler  where thOur findings were similar to Malamed et al. , whose tIn a general evaluation, the similarity of effectiveness of the anesthetics used in postoperative pain control is well established, being based on the patient’s analgesic consumption that presented an equivalent ratio. When considering that pain manifests more intensely in first 12 hours with the peak generally being observed around the 6th, 8th hours -22, thisNo significant differences were observed between the tested anesthetic solutions for postoperative pain control in third molar surgery, with the use of the Visual Analogue Scale, the McGill Pain Questionnaire and the consumption of analgesics as published in Evans et al.  report aResearch based on these pain control parameters is difficult to standardize, due to the pain threshold of each patient, as well as degree of difficulty of patients to understand the instructions for filling out the questionnaire. It is suggested that further research must be conducted with higher number of patients.


Previous studies of long-term treatment response in fibromyalgia and other chronic pain states have generally been limited to approximately one year, leaving questions about the longer-term durability of response. The purpose of this study was to demonstrate continuing efficacy of milnacipran by characterizing changes in pain and other fibromyalgia symptoms after discontinuing long-term treatment. The mean length of milnacipran treatment at the time of randomized withdrawal was 36.1 months from initial exposure to milnacipran .After completing a long-term, open-label, lead-in study of milnacipran (which followed varying periods of exposure in previous studies), adult patients with fibromyalgia entered the four-week open-label period of the current study for evaluation of ongoing treatment response. After the four-week period to confirm new baseline status, 151 patients taking milnacipran ≥100 mg/day and reporting ≥50% improvement from pre-milnacipran exposure in Visual Analogue Scale (VAS) pain scores were classified as responders. These responders entered the 12-week, double-blind withdrawal period in which they were randomized 2:1 to continue milnacipran or switched to placebo. The prespecified primary parameter was loss of therapeutic response (LTR), defined as increase in VAS pain score to <30% reduction from pre-milnacipran exposure or worsening of fibromyalgia requiring alternative treatment. Adverse events and vital signs were also monitored.P < 0.001). Median time to LTR was 56 days with placebo and was not calculable for milnacipran, because less than half of the latter group of patients lost therapeutic response by study end. Additionally, 81% of patients continuing on milnacipran maintained clinically meaningful pain response (≥30% improvement from pre-milnacipran exposure), compared with 58% of patients switched to placebo . The incidences of treatment-emergent adverse events were 58% and 47% for placebo and milnacipran, respectively. Mean decreases in blood pressure and heart rate were found in both groups, with greater decreases for patients switched to placebo.Time to LTR was shorter in patients randomized to placebo than in patients continuing milnacipran (Continuing efficacy of milnacipran was demonstrated by the loss of effect following withdrawal of treatment in patients who received an average of three years of milnacipran treatment.NCT01014585ClinicalTrials.gov:  Fibromyalgia is a complex disorder characterized by chronic widespread pain, fatigue, stiffness, poor sleep, depressed mood and cognitive difficulties -3. On thCentrally acting analgesics, such as the tricyclic compounds, were investigated once it became clear that the diffuse pain and other symptoms of fibromyalgia were likely due to aberrations in the central nervous system. Preliminary studies with amitriptyline and cyclobenzaprine showed efficacy in patients receiving one to three months of treatment ,10. ThesAs the pathophysiology of fibromyalgia became better understood, research focused on other centrally acting analgesics that would likely improve this condition . This leAlthough treatment benefits were found in the extension studies and the open-label milnacipran study, none included a placebo control group, because placebo-controlled, parallel-group clinical trials are ethically and practically difficult to conduct over long periods of time in patients with chronic pain. Therefore, this randomized withdrawal study was conducted to investigate the effects of discontinuing treatment of fibromyalgia patients who had completed participation in the long-term, open-label milnacipran study . This deEnrollment began on 20 November 2009, and the last patient visit was completed on 7 June 2010. The study was conducted at 58 US centers and approved by the institutional review board or ethics committee at each site , twelve weeks with patients randomized to milnacipran or placebo (double-blind) and one week of tapering (double-blind). After the four-week open-label period, patients receiving a minimum dosage of milnacipran 100 mg/day and achieving ≥50% pain improvement from pre-milnacipran exposure  pain score prior to any milnacipran treatment in any study) were classified as responders and randomized (2:1) to continue milnacipran at the same dosage or were switched to placebo. Pain improvement was assessed using 24-hour recall VAS pain scores . The 50% threshold was not selected as a benchmark for clinically meaningful pain reduction, but rather to enrich the population of responders so that loss of response after randomization  could be measured. Patients not meeting the protocol-defined responder criteria were also randomized and followed in the study. However, because these patients were not the primary focus of the study, their results are not presented in this report.Randomization codes were generated and securely stored by Forest Research Institute, Inc . An interactive voice and/or web response system was used to calculate the mean pain intensity score during the last week of the open-label period, to allocate patients to the appropriate responder or nonresponder population and to dispense investigational medications, which were sealed and coded to maintain the double-blinding.The primary efficacy parameter was time to loss of therapeutic response (LTR), defined as time from baseline (randomization) to the first double-blind study visit in which a patient had <30% reduction in VAS pain from pre-milnacipran exposure or worsening of fibromyalgia requiring alternative treatment, as judged by the study's principal investigator. The 30% threshold was based on an accepted definition of clinically meaningful pain reduction . PatientSecondary efficacy parameters included time to worsening based on the Patient Global Impression of Change (PGIC) and the Multidimensional Assessment of Fatigue (MAF) global fatigue index . Based oAdditional efficacy parameters included time to worsening in Short Form-36 Health Survey (SF-36) Physical Component Summary (PCS) and Mental Component Summary (MCS) scores , with woAdverse events, vital signs and clinical laboratory tests were monitored for safety. Treatment emergent adverse events were defined as adverse events that occurred after the first dose of double-blind treatment or increase in severity during this period. Efficacy and safety assessments were conducted at all study visits with the exception of PGIC, which was assessed at weeks 2, 4, 8 and 12 of the double-blind period.Assuming that 60% of the placebo and 35% of the milnacipran groups would experience LTR by end of the double-blind period, it was estimated that 180 enrolled patients (placebo = 60 and milnacipran = 120) would be needed to detect a 25% difference between treatment groups with 90% power at the two-sided 5% significance test. The safety population included all randomized patients who received one or more doses of double-blind treatment. The intent-to-treat population included patients in the safety population who had one or more postrandomization pain assessments. Kaplan-Meier estimates were used to analyze time to LTR and time to worsening based on PGIC, MAF, SF-36 PCS and SF-36 MCS scores, with comparisons between treatment groups analyzed using the logrank test. Hazard ratios (HRs) with 95% confidence intervals (95% CIs) were calculated using a Cox proportional hazards model with treatment group as the explanatory variable. Patients who completed the study without experiencing LTR or who withdrew for any reason other than LTR were censored in the primary efficacy analyses.An analysis of covariance model was used to calculate mean changes from randomization, with treatment group and study center as factors and baseline value as a covariate. Missing data were imputed using the last observation carried forward approach. Tests were two-sided performed at the 5% level of significance. Descriptive statistics were used to analyze changes from randomization in vital signs and clinical laboratory values, with the end of the study defined as the last available assessment in the double-blind period. All analyses were performed using SAS version 9.1.3 software .n = 100) or switched to placebo (n = 51)  were classified as responders and randomized to continue milnacipran  . In addition, the percentage of patients maintaining 30% or more pain improvement from pre-milnacipran exposure was 81% in the milnacipran group and 58% in the placebo group . The only nonsignificant finding was for sensitivity analysis III, which simply defined LTR as worsening of fibromyalgia requiring alternative treatment.Patients discontinuing milnacipran had significantly shorter time to LTR than patients who continued treatment . In addition, mean least squares changes from randomization indicated greater worsening in VAS pain, BPI average pain, FIQR and SF-36 PCS scores with placebo versus milnacipran, with significant between-group differences observed at all study visits (P < 0.05) , nasopharyngitis (2.5%) and nausea (2.5%). No serious adverse events occurred during this period, and two patients discontinued due to adverse events (one with nausea and one with hypertension). During the double-blind period, 47% of patients continuing milnacipran and 58% of patients switched to placebo reported one or more treatment emergent adverse events , diastolic blood pressure  and pulse . Potentially clinically significant changes in vital signs were found in one patient receiving milnacipran  and one patient receiving placebo . No potentially clinically significant change in laboratory parameters occurred in more than two patients in either treatment group.Future Revascularization Evaluation in patients with Diabetes Mellitus: Optimal Management of Multivessel Disease (FREEDOM) study of pregabalin in fibromyalgia [Because it can be difficult to conduct long-term, placebo-controlled, parallel-arm studies to assess the efficacy of chronic pain medications, we used a randomized, placebo-controlled, withdrawal design in this trial to evaluate the loss of therapeutic response in patients with fibromyalgia who discontinued long-term treatment with milnacipran. As in other withdrawal studies , includiomyalgia , the preomyalgia .P < 0.001).In the current study, we analyzed data from patients who achieved ≥50% pain improvement after receiving 1.5 to 4.5 years  of milnacipran treatment in one or more prior clinical trials. Milnacipran dosages had been optimized for each patient entering the withdrawal study (50 mg/day to 200 mg/day), although the present analyses were limited to patients receiving at least the minimum recommended dosage of 100 mg/day . The resThe primary endpoint, as well as two of the three sensitivity analyses, included either worsening of fibromyalgia or discontinuation from the study as a definition of LTR. Sensitivity analysis II, however, was based solely on the pain criterion . The results of this analysis, in conjunction with analyses of mean pain scores at various time points , may provide some important insights about pain responses in patients who had received up to 4.5 years of prior milnacipran treatment. First, notable pain improvements were found in patients who received long-term milnacipran treatment, as indicated by the 73% decrease in mean VAS pain score from pre-milnacipran exposure (65.7%) to randomization 17.5%) (Table 7.5% Tab. AlthougP < 0.001). These findings were supported by mean worsening from randomization in FIQR and SF-36 PCS scores, which were significantly worse with placebo than milnacipran at every study visit.This study also demonstrated that improvements in global status (PGIC), fibromyalgia severity (FIQR) and physical functioning (SF-36 PCS) occurred in patients receiving long-term milnacipran treatment. A higher percentage of patients discontinuing milnacipran reported feeling "much worse" or "very much worse" since randomization as compared with patients who continued treatment  should expect to continue to require long-term treatment.No unexpected safety issues were observed in this study. Nausea and headache, the most commonly reported treatment emergent adverse events with milnacipran in placebo-controlled trials ,26,39 anA few limitations should be noted. First, on the basis of the results reported above, no conclusions can be drawn about the effects of discontinuing milnacipran in patients who did not meet the stringent ≥50% pain responder criterion. However, subsequent analyses of this study indicate that patients who had 30% to <50% pain improvement from pre-milnacipran exposure, which indicates clinically meaningful improvement, also experienced loss of therapeutic effect after milnacipran was discontinued . Second,In patients who received milnacipran for an average of three years , loss of therapeutic response upon discontinuation of treatment provides evidence of long-term efficacy of this medication for the management of fibromyalgia.BPI: Brief Pain Inventory; FIQR: Revised Fibromyalgia Impact Questionnaire; LTR: loss of therapeutic response; MAF: Multidimensional Assessment of Fatigue; MASQ: Multiple Ability Self-Report Questionnaire; MCS: Mental Component Summary; PCS: Physical Component Summary; PGIC: Patient Global Impression of Change; SF-36: Short Form-36 Health Survey; VAS: Visual Analogue Scale.DJC has received grants and research support from Pfizer Inc and Forest Laboratories. He has been a consultant for and has served on advisory boards for Pfizer Inc, Eli Lilly and Co, Forest Laboratories, Inc, Cypress Bioscience, Inc , Pierre Fabre Pharmaceuticals, UCB and AstraZeneca. PJM has received research and grant funding as well as consultation fees from Forest Laboratories, Inc, Cypress Bioscience, Inc, Eli Lilly and Co, Pfizer Inc, Allergan, Inc, Wyeth Pharmaceuticals, Jazz Pharmaceuticals and Fralex Therapeutics. In addition to being full-time employees of Forest Research Institute, Inc, a wholly owned subsidiary of the study sponsor , RHP, JMT and YW hold stock in the parent company.DJC and RHP contributed the design of this study. JMT was the study director. PJM was a principal investigator of the study. YW performed statistical analyses of the data. All authors had full access to the data and participated in the interpretation of study results. All authors were also involved in drafting and revising the manuscript. All authors approved the final manuscript for publication.List of Institutional Review Boards and Study Centers.Click here for file


Little is known about the integration of acupuncture for chronic pain in primary care settings, especially in low income and minority communities. The purpose of this ongoing NCCAM-funded study was to explore the feasibility and effectiveness of adding acupuncture to routine management in the primary care setting for diverse, low income chronic pain patients.Primary care physicians at four community health centers in the Bronx, NY referred adult patients with chronic pain due to osteoarthritis, neck or back pain for acupuncture. The acupuncture was offered weekly for up to 14 weeks at the primary care sites, delivered by student/preceptor teams from the Swedish Institute and the Pacific College of Oriental Medicine. Using a repeated measures design we evaluated changes in pain and function over a 6-month period as compared to baseline. Outcome measures were collected during a 6-week pre-treatment phase for baseline measures and then at 2, 4, 8, 12, and 16 weeks, with a final assessment at 6 months.Regarding feasibility, we received over 400 referrals, reflecting a high level of interest in acupuncture services from both clinicians and patients. We also found that acceptability was high in that patients who began treatment tended to continue treatment, with a mean number of treatments per patient over 7. Regarding effectiveness, a preliminary analysis of completers to date found that pain severity and physical well-being were significantly improved from baseline at the six month follow-up. Mean BPI severity score decreased from 6.64 to 5.37 . Mean SF-12 physical well-being score increased from 31.61 to 35.51 .Acupuncture can be delivered in the primary care setting to chronic pain patients in an underserved area. A preliminary analysis shows that it can be effective in reducing pain and improving quality of life.


Adequate post-operative pain relief following total knee replacement (TKR) is very important to optimal post-operative recovery. Faster mobilisation and rehabilitation ultimately results in optimum recovery outcomes, but pain is often the limiting factor. This study evaluates the potential clinical benefit of the InterX neurostimulation device on pain reduction and rehabilitative outcome.A clinical trial under the Hywel Dda Clinical Audit Committee to validate the clinical benefit of Non-invasive Interactive Neurostimulation (NIN) therapy using the InterX device was performed in patients undergoing TKR. 61 patients were randomised to treatment groups in blocks of two from the Theatre Operation List. The control group received the standard hospital course of pain medication and rehabilitation twice daily for 3 post-op days. The experimental group received 8 sessions of NIN therapy over 3 post-op days in addition to the standard course received by the Control group. Pain and range of motion were collected as the primary study measures.Sixty one subjects were enrolled and randomised, but 2 subjects (one/group) were excluded due to missing data at Baseline/Final; one subject in the InterX group was excluded due to pre-existing rheumatoid pain conditions confounding the analysis.The experimental group pre- to post-session Verbal Rating Scale for pain (VRS) showed that NIN therapy consistently reduced the pain scores by a mean of 2.3 points (SE 0.11). The NIN pre-treatment score at Final was used for the primary ANCOVA comparison, demonstrating a significantly greater cumulative treatment effect of a mean 2.2 (SE 0.49) points pain reduction (p = 0.002). Control subjects only experienced a mean 0.34 (SE 0.49) point decrease in pain. Ninety degrees ROM was required to discharge the patient and this was attained as an average despite the greater Baseline deficit in the InterX group. Eight control patients and three experimental patients did not achieve this ROM.The results clearly demonstrated the clinical benefit of NIN therapy as a supplement to the standard rehabilitation protocol. The subjects receiving InterX fared significantly better clinically. Within a relatively short 3-day period of time, patients in the experimental group obtained the necessary ROM for discharge and did it experiencing lower levels of pain than those in the control group. Adequate post-operative pain relief following total knee replacement (TKR) is very important to optimal post-operative recovery. The fasCurrent pharmaceutical pain relief options for TKR pain have limitations due to associated side effects, often requiring additional treatment for them. Side-efHistorically, electrical stimulation modalities, such as transcutaneous electrical nerve stimulation (TENS), have been used to manage pain and facilitate recovery from various traumatic conditions-12. In gThere are a number of factors that may contribute to the lack of efficacy of TENS in this application. Literature has shown that the variables of electrode placement-18, freqThere is increasing evidence that successful optimization of electrode position, amplitude and frequency parameters in a dynamically changing pattern may well be the key critical to successful therapeutic outcomes-27. The The InterX device operates by scanning the tissue to determine its impedance and to use the electrical characteristic of the skin to identify and target optimal treatment points. As stimulation is performed, the impedance of the skin under the electrode changes and is sensed by the device through the completed electrical circuit which in turn automatically varies the waveform parameters. Different preset stimulation patterns are selected in subsequent therapy sessions to prevent physiological accommodation and each of these presets automatically delivers a varying frequency to ensure optimal effects. The preThe handheld application of NIN has previously been shown to significantly reduce pain, medication intake and inflammation while also increasing range of motion following hip and ankle surgery,26. In tThe objective of this investigation was to observe whether greater post-operative pain relief and range of motion (ROM) could be obtained by using the InterX 1000 device and Flexible Array Electrodes when combined with standard in-hospital rehabilitation protocols in patients undergoing primary TKR surgery as compared to standard in-hospital rehabilitation methods alone. Primary study endpoints (pain severity and knee range of motion (ROM)) would ideally show a reduction in pain severity and greater ROM in the InterX treatment group. Secondary endpoints (pain medication use and signs of inflammation) could result in a reduction in medication use and in knee joint inflammation. Circumferential measures of the knee were taken to try to demonstrate any possible changes in signs of inflammation. There is controversy about the reliability of this measure but we felt there was enough evidence to include this in the study as it has been used recently along with both skin temperature and inflammatory biomarkers in patients ,35.This randomised, controlled, prospective study was conducted under the Hywel Dda Clinical Audit and Risk Committee as it was performed to demonstrate the efficacy of a recognized technology on a new population of patients. The clinical audit passed ethics review through the Audit and Risk Committee. All subjects signed informed consent. The control group received the standard in-hospital rehabilitation protocol while the experimental group received standard in-hospital rehabilitation plus eight sessions of NIN therapy. Subjects were randomised to treatment group by the Theatre Operation List whereby subjects were randomly assigned treatment group by the order in which they were operated, alternating treatment group assignment in blocks of two.61 subjects were enrolled into the study following elective total knee joint replacement from the orthopaedic clinic in the catchment area of Prince Philip Hospital, Carmarthenshire NHS Trust in Wales, UK. Surgery was performed using two main types of knee implant (cruciate retaining and cruciate sacrifice). Inclusion criteria specified that patients were to be 50-80 years of age with radiographic evidence of joint disease in at least 2 of the 3 knee compartments  who were scheduled for elective TKR. Subjects were to have no associated neurological deficit, sensory loss, paraesthesia, or hyporeflexia. Subjects were to have a clinically significant functional limitation (limited mobility and/or instability of the knee joint) and diminished quality of life prior to TKR. Additionally, subjects had to be willing to abide by the protocol and treatment schedule and sign informed consent. Subjects with local or systemic infections, medical conditions that substantially increase the risk of serious peri-operative complications or death were excluded from the study. Subjects with implanted neurostimulators, insulin pumps, and/or cardiac pacemakers were excluded due to the incompatibility of treatment with an electrical nerve stimulator. Subjects with epilepsy/seizure, dementia or cognitive disorders, pregnancy, psychiatric disease, active tumour or cancer, fracture or dislocation, or at substantial risk of venous thrombosis were also excluded from the study. Signs of venous thrombosis like redness and pain in the lower leg usually become evident within 72 hrs of surgery if they are going to occur. If the Physician saw any of these signs then treatment with the InterX was to be halted.Subjects had standard operative anaesthesia to include general anaesthesia with either spinal anaesthesia or with femoral nerve block during the procedure. The nerve block was a single shot using morphine with doses ranging from 150-250 mcg. Post-operatively, pain was to be mediated from surgery to Day 2 by patient controlled analgesia (PCA) morphine (1 mg/mL) strictly monitored by a nurse, diclofenac suppositories (Volterol) and acetaminophen (Paracetamol). After 48 hrs, patients were stepped down to codeine with acetaminophen (Cocodamol) and diclofenac suppositories (Volterol) plus oral morphine for breakthrough pain. The medication was offered to patients and provided on an as needed basis (prn).All subjects were followed for three days in-hospital prior to discharge to home. While in-hospital, the subjects underwent in-hospital rehabilitation exercises twice daily to include the following. On day one, subjects are transferred to a chair and try walking with a walking frame and they perform ROM exercises. On day two, subjects perform ROM exercises, walking with a frame and then walking with support using canes. On day three, subjects go to occupational therapy and do stair climbing, mimic getting in and out of a car, and walk with cane support. The goal is to get to 90° flexion.Subjects randomised to the experimental group received NIN therapy according to the following schedule: Day 0 (0-24 hrs post-op), no treatment due to bandaging; Day 1 (24-48 hrs post-op), two InterX treatments of twenty minutes each using Preset 4 at approximately 1 pm and 4 pm; Day 2 (48-72 hrs post-op), three InterX treatments of 20 minutes each using Preset 4 ; Day 3 (72-96 hrs post-op), three InterX treatments of 20 minutes each using Preset 1 . Baseline measures are those taken on Day 1 at approximately 1 pm . Final measures are those taken on Day 3 at approximately 4 pm prior to the final treatment.NIN therapy was delivered via two InterX 1000™ devices, each with a Dual Flexible Array Figure . Each arIn the initial version of the protocol, the study measurements were assessed at each time point. However, because of the time involved in study measurement collection imposed on the nursing/rehabilitation routines, the protocol was amended to collect ROM and knee circumference data only at the first (Baseline) and last  study time period. VRS was recorded at every treatment and medication was recorded as taken. The primary study variables were designated as the VRS and ROM; secondary study measures included the total daily pain medication taken and knee circumference. Study measurements were taken at 9 am, 1 pm and 4 pm for the control group, and just prior to and following NIN therapy administration at those same times for the experimental group.Subjects verbally rated the intensity of their knee pain using an 11-point numeric scale . This scale, similar to the Visual Analogue Scale (VAS), has demonstrated validity and reliability. At BaseKnee flexion was measured by the nurse using a standard goniometer (20 cm Jamar-E-Z by Physiomed). At Baseline and Final, all subjects were measured. Experimental group subjects were measured pre- and post-treatment at each time point. Control subjects had only a single measurement at each time point. Patients were seated and asked to actively flex their knee as far as pain would allow. This flexion was then measured by the nurse practitioner.The dose and frequency of all pain medications were recorded daily for all patients in mg for PCA morphine use and for diclofenac suppositories, and pill counts for acetaminophen, and codeine with acetaminophen using standardized dosage forms.The circumferential girth at 2 inches above the knee of both the affected and unaffected knees was measured. The un-operated knee measurement was subtracted from the operated knee measurement as a possible indicator of signs of inflammation of the operated knee. These measures were made at Baseline and Final time points for all patients.The trial's sample size was determined based on observed variation in pain scores from earlier studies, and the investigators' judgment that a two-point reduction in reported pain  represented a clinically meaningful result. It is generally accepted that a 30% reduction of pain in acute cases represents a clinically meaningful change, so a twpost-hoc. Ultimately, 28 subjects in the experimental group and 30 subjects in the control group are included in the below analyses  was analysed on the change in ROM between Baseline and Final Figure . An analTable In retrospect, it is believed that this measure in this situation was probably an inappropriate measure to include because the goal of post-operative pain medications in a procedure of this magnitude, is to stay ahead of the pain and so standard administration of pain medicines at regular intervals are administered by hospital staff regardless of the subject's level of pain. It is noteworthy that the experimental group, who started with higher levels of pain at Baseline, reported lower levels of pain, or no pain, using the same amount of pain medications as the control group who were reporting no significant relief from pain. It was deemed not possible to convert the different types of medications into one measure as they included opioids and NSAIDs. So this data stands as a backdrop to demonstrate that the pain reduction seen in the experimental group was due to the NIN treatment and not due any variations in medication intake. It should be noted that the experimental group did take less medication than the control (see Table The effect of treatment (NIN vs. control) was analysed on the change in inflammation (measured as the difference between circumferences of the non-operated and operated knees) between the Baseline and Final. An analysis of covariance was used with the inflammation measured during the Baseline serving as the covariate term. The treatment effect was not significant (p = 0.44), with an adjusted mean change for the experimental group of 1.11 cm vs. an adjusted mean change for the control group of 1.59 cm. The standard error of the estimated difference between the two groups (0.48) was 0.67. Note that both groups experienced an increase in the circumference of the affected knee following the surgery as is normal for this type of invasive procedure. The difference between treatment groups at Final is consistent with the difference seen at Baseline. However, it should be noted that the experimental group took on average 27% less NSAIDs. The average change in knee circumference was very small and almost within the normal variations expected with repeated measures, which may indicate that this circumferential method in this study may not have been a reliable way to measure changes in inflammation. So whilThis study was undertaken as an audit of the Hywel Dda NHS Trust in Wales to validate the clinical benefit of NIN therapy as a supplemental rehabilitative therapy following TKR. The hospital currently uses NIN therapy as a standard course of therapy in the chronic pain clinic. The results of this study clearly demonstrated the clinical benefit of NIN therapy with the InterX device as a supplement to the standard in-house rehabilitative protocol for patients following TKR. By random assignment to treatment group, subjects with more severe pain and more ROM-restricted were placed in the InterX group. Within a relatively short 3-day period of time, patients in the InterX group obtained the necessary ROM for discharge and did it experiencing significantly reduced levels of pain compared to those in the control group.only if it used optimally and that amplitude and frequency appear to be the most important variables. Secondly, that TENS is only effective for partial pain relief whereas analgesic pharmaceuticals have the potential for complete pain relief, though side effects often mitigate this. Typically, TENS has been considered effective only if the supplemental use of TENS results in a reduction of analgesic consumption without increased pain scores. In Bjordal's article, it is suggested that a positive outcome also occurs when there is a decrease in pain scores, but the analgesic consumption (at a tolerable level) is maintained. The author also mentions that the best treatment effects were observed using the higher frequencies of TENS at 85 Hz and at an amplitude of > 15 mA or a strong sensation to the patient.In making conclusions regarding the effectiveness of electrical stimulation to counteract pain, several relevant ideas have been discussed by Bjordal  in the mWithin this study, the latter scenario was observed. Subjects here experienced greater pain relief on tolerable pain medication regimens. The greater pain relief seen in this study allowed the patients to push harder in rehabilitation to reach the discharge criteria since the InterX treatment group was clinically more severely hampered with pain and ROM restrictions at Baseline. It should be noted that the InterX was used at a variable frequency covering the optimal range suggested by Bjordal et al and also at an amplitude in the range of > 40 mA. It is oEvidence shows that InterX NIN therapy probably activates the gate control mechanism of pain control, but due to the short treatments, long-lasting effects and cumulative reductions in pain reported by patients, gate control probably is not the primary mechanism of pain relief-27. InteThe results of this study clearly demonstrated that the delivery of NIN through the Flexible Array Electrode is effective for the management of pain in this population of patients, supporting previous literature pertaining to the handheld application of NIN in the post-surgical setting. The InterX is designed to optimize treatment point location, amplitude and frequency to ensure better clinical results and this technological aspect is maintained in this application. The clinical benefit of NIN therapy with the InterX device as a supplement to the standard in-house rehabilitative protocol allows patients suffering pain to regain function quicker, especially if their pain levels are particularly high. Even though subjects with more severe pain and more ROM-restriction were randomly assigned to the InterX group, the subjects receiving NIN therapy with InterX fared much better clinically with significantly reduced pain levels and improvements in ROM compared to control subjects. The implications of these findings are that patients suffering severe pain following TKR struggle to get sufficient relief from the standard of care of medications and that the inclusion of NIN therapy into the standard of care will offer greater and more consistent pain control, without the need for increased medication even with the worst cases.ANCOVA: analysis of Covariance; cm: centimetres; MANOVA: multivariate test of differences; NSAIDS: nonsteroidal anti-inflammatory drugs; NIN therapy: non-invasive interactive neurostimulation; PCA: patient controlled analgesia; ROM: range of motion; TENS: transcutaneous electrical nerve stimulator; TKR: total knee replacement; VRS: verbal rating scaleThe author(s) AN and DT declare that they have no competing interests. Author ZV is a paid consultant for Neuro Resource Group and holds shares in the company, although she was not involved in collection or interpretation of data.AN was the principle investigator and oversaw the implementation of the protocol. DT performed all treatments, measurements and data collection. ZV assisted in the development of the study protocol only. All authors have read and approved the final publication article.