Current studies comparing musculoskeletal pain levels between the genders focus on a single point in time rather than measuring change over time. The purpose of this study is to compare pain levels between males and females before and after treatment.U test was used to calculate differences in numerical rating scale (NRS) median scores between the genders for both time points in all 11 cohorts.Eleven different patient cohorts  included in two prospective outcome databases collected pain data at baseline and 1 month after treatment. Treatments were either imaging-guided therapeutic injections or chiropractic therapy. The Mann–Whitney Females reported significantly higher baseline pain scores at 4 of the 11 sites evaluated , subacromial (p = 0.002), knee (p = 0.023) injections sites and chiropractic low back pain (LBP) patients (p = 0.041)). However, at 1 month after treatment there were no significant gender differences in pain scores at any of the extremity sites. Only the chiropractic LBP patients continued to show higher pain levels in females at 1 month.In these 11 musculoskeletal sites evaluated before and after treatment, only 3 extremity sites and the chiropractic LBP patients showed significantly higher baseline pain levels in females. At 1 month after treatment only the LBP patients had significant gender differences in pain levels. Gender evaluation of change in pain over time is likely to be more clinically important than an isolated pain measurement for certain anatomical sites. While everyone with an intact nervous system experiences physical pain, research has shown that the reported intensity and prevalence of pain arising from the musculoskeletal system appears to differ between males and females,2. SpeciTwo recent systematic reviews of the literature looking at these gender differences in an experimental environment concluded that males have significantly more efficient diffuse noxious inhibitory controls (DNIC) compared to females and females are less tolerant to thermal stimuli and pressure pain, but not to ischemic pain. But the weight of the evidence does not show a clear and consistent pattern of gender differences in pain sensitivity,8. HowevThis specialized orthopaedic/rheumatology university hospital began collecting prospective outcomes data during 2009–2010 and this is ongoing in both the radiology and chiropractic departments in order to create large databases for research and quality assurance purposes. Patients undergoing imaging-guided therapeutic musculoskeletal injections and patients being treated by chiropractors for neck pain, low back pain, and imaging confirmed symptomatic disc herniations are included in these databases. Because the literature consistently reports gender differences in pain levels and prevalence based on anatomical region, assumptThis is a prospective outcomes study with 1 month follow-up on 11 different cohorts of patients using two large databases, one from the radiology department and the other from the chiropractic department. The study was conducted in a specialized orthopaedic/rheumatology university hospital. Ethics approval was obtained from the Canton of Zürich ethics commission prior to the start of the databases  and all patients signed informed consent immediately prior to their therapeutic intervention. No patient was included in any of the databases more than once.Consecutive patients over the age of 18 with pain strongly suspected to arise from the particular joint, nerve root or spinal canal targeted for injection and who had not responded to conservative treatments were included. Exclusion criteria included joint injections not intended for pain therapy . Patients with overlying skin infections or who were pregnant were also excluded. Patients on anticoagulants were excluded from having spine injections but not from the peripheral joint injections.Only those imaging-guided injection sites with at least 100 patients in the current database were included for analysis in order to limit this study to the most common MSK injection sites. This included cervical indirect nerve root blocks, lumbar epidural injections, lumbar facet joint injections, and lumbar nerve root blocks for the spine. Extremity injection sites included the gleno-humeral, subacromial, knee and hip joints.New patients over the age of 18 with back pain, neck pain, or magnetic resonance imaging (MRI) confirmed symptomatic lumbar disc herniation of any duration who had not received chiropractic or manual therapy in the prior 3 months were recruited from multiple chiropractic practices in Switzerland. Patients with specific abnormalities of the lumbar spine that are contraindications to chiropractic manipulative treatment, including tumors, infections, inflammatory spondylo-arthropathies, acute fractures, Paget’s disease and severe osteoporosis were excluded.Only the treatment sites with a minimum of 100 patients in the database were included in this study. Neck pain patients, low back pain patients, and patients with the specific MRI confirmed diagnosis of symptomatic lumbar disc herniation met this criterion. Patients in the cervical disc herniation database were not included due to the current small sample size.Under imaging guidance, a needle was placed into the relevant joint, adjacent nerve root or lumbar interlaminar space. A non-neurotoxic contrast agent was then injected to confirm correct needle placement. Once correct needle placement was confirmed, an injection of a local anesthetic (Naropin 0.2%) was delivered, followed by an injection of corticosteroid Figures  and2. TThirty two different Swiss chiropractors contributed patients to the chiropractic outcomes database and no individual data was collected concerning the specific treatments offered to each patient. However, data collected from the Swiss Job Analysis Study of chiropractors in 2009[The eleven point NRS  where 0 is no pain and 10 is the worst pain imaginable was used for all patients in the two databases. This value was recorded for the level of current pain in the radiology department immediately prior to the imaging-guided therapeutic injection or in the respective chiropractic clinics prior to the chiropractic treatment procedure. One month after the first treatment, patients who had received an imaging-guided therapeutic musculoskeletal injection returned a paper-based postal questionnaire which included information on their current pain level using the NRS scale. Chiropractic patients had this exact same data collected one month after the first treatment via telephone calls from trained independent research assistants. Data was manually entered into SPSS version 17.0 by one of the authors and one research assistant.U test was used to assess for significant differences between the genders for baseline NRS, 1 month NRS, and the NRS change score median values at 1 month for each region. P < 0.05 was determined to be significant. However, the mean values rather than the median values are reported in the tables to make the data easier to relate to the NRS scale and for comparison with other prior studies. Spearman’s correlation coefficient was used to evaluate the relationship between age and baseline NRS scores for each of the 11 cohorts.Means and standard deviations (SD) were calculated for the two data collection time points by gender for each injection and chiropractfic treatment site. Because the NRS data was skewed toward the upper end of the pain scale, the non-parametric Mann–Whitney Data was available for 3,900 patients, 1,954 from the imaging-guided therapeutic injections database and 1,946 from the chiropractic treatment database. Of these patients 1,855 (48%) were males. Of the four spinal injection sites, there was a higher prevalence of females for both epidural (61%) and lumbar facet (55%) injections Table . Fifty sIn the chiropractic treatment database, a strong prevalence of female patients was found for neck pain (62%) but a very slight male predominance (51%) was noted for low back pain patients. The lumbar disc herniation patients showed a very strong male prevalence of 79%.Comparing the two genders for the imaging-guided spinal injections showed no significant differences in baseline NRS scores, 1 month NRS scores, or 1 month NRS change scores for any of the injection sites Table . HoweverFor the patients undergoing chiropractic treatment for low back pain (n = 1065), there was a significant difference in the baseline pre-treatment NRS scores between males and females (p = 0.041) with females reporting higher scores. At 1 month the difference between the genders was higher (p = 0.001) Table . ChiroprAssessing for significant age differences between the genders for each of the 11 musculoskeletal sites found that females were significantly older for 3 of the imaging-guided injection sites and males were significantly older for chiropractic patients treated for low back pain Table . None ofTo our knowledge, this is the first study to specifically compare reported pain levels between males and females at specific anatomical sites before and after various musculoskeletal therapies using a large electronic database. Of the 11 musculoskeletal sites evaluated, females reported significantly higher baseline pain levels prior to gleno-humeral, subacromial and knee injections as well as LBP patients undergoing chiropractic treatment. However at 1 month after treatment there was no significant difference in NRS scores between the genders for the 3 extremity injection sites, indicating a better response for women. Only the LBP patients receiving chiropractic treatment continued to show the same gender difference in pain levels at one month. Although this may appear to support previous studies claiming that women report higher pain intensity compared to men,4,5, it reduction levels with treatment rather than meaningful differences in pain levels between subgroups at the same time point[Although there were statistically significant differences in baseline pain levels between the genders for 3 extremity injection sites and for chiropractic LBP patients, an important question to ask is whether or not these numerical differences are actually clinically relevant? Most previous studies reporting on gender differences in pain levels have not addressed this issue-6. Indeeme point-12. It hme point. HoweverOf the 7 different spinal sites evaluated before and after treatment, the only significant difference in outcome was for chiropractic patients treated for low back pain. Unlike previous European studies which reported that females have a higher prevalence of low back pain,13-17, iIt is well established that males are more likely to have lumbar disc herniations,19. HoweThe majority of neck pain patients in the chiropractic database were female (62%) as expected based on previous research, but forThe main limitation to this study is the fact that only patients presenting for specific treatments involving the musculoskeletal system were included due to the availability of information from large databases. Extrapolation of these results to other anatomical sites or treatments cannot be done without additional research. Furthermore, for most of the 11 sites assessed, specific diagnoses were not easily available or confirmed. Further research into differences in reported pain levels based on gender for patients with confirmed diagnoses or specific abnormalities observed on diagnostic imaging would be valuable.Additional demographic variables should also be considered when comparing the genders for pain differences. These could include factors such as duration of pain, ethnicity, work status, body mass index, level of physical activity and medication usage. This information was not available for most of these current patients and represents another limitation. Comparison of pain differences by age categories was also not done in this study and could potentially be relevant as increasing age has previously been shown to increase pain sensitivity. HoweverOnly those anatomical treatment sites that had at least 100 patients in the database were assessed for this study. This occurred for two reasons. The first was to make sure that the sample sizes were large enough to detect any gender differences. The second reason was pragmatic as there are currently 67 different MSK injection sites with data in the radiology database, some with only a few patients. It was felt that including most of these anatomical sites in this study at this time would not add meaningful information.Additionally, as these were all prospective outcomes studies rather than randomized clinical trials, the improvement in pain levels and overall outcomes cannot definitively be attributed to any of these treatments. Another limitation is that only change in pain at 1 month after treatment was measured rather than longer-term outcomes. However, chiropractic studies at least, have shown that if patients are likely to improve, they do so quite quickly after the start of treatment-24.Although 4 of the 11 musculoskeletal areas evaluated found that women had significantly higher baseline pain scores, three of which were extremity injection sites, at 1 month post-injection there were no gender differences in pain levels for these three sites. Only LBP patients receiving chiropractic treatment demonstrated statistically significant gender differences in baseline and 1 month pain levels. The actual numerical differences in the pain scores that did show statistically significant differences were not large, particularly for the chiropractic LBP cohort. It is therefore questioned whether or not these baseline gender differences in pain levels are actually clinically relevant. This shows that it may be important to measure pain levels over time, at least for certain anatomical sites, to obtain an accurate clinical picture. Although chiropractic patients suffering from neck pain were predominately women, there were no differences in baseline pain scores or any outcome measure at 1 month compared to men. It cannot be ruled out however, that the gender differences observed were due to differences in other covariates that were not measured due to their lack of availability. Future studies comparing pain levels between the genders should explore differences in adjusted models.The authors declare that they have no competing interests.C K. P: Conception and design of the study; analysis and interpretation of data; drafting the manuscript. B. K H: Conception and design of the study; revising manuscript critically for important intellectual content; final approval of the version to be published. J H: Performance of imaging-guided injection procedures; revising manuscript critically for important intellectual content; final approval of the version to be published. C W. A. P: Performance of imaging-guided injection procedures; revising manuscript critically for important intellectual content; final approval of the version to be published. All authors read and approved the final manuscript.The pre-publication history for this paper can be accessed here:http://www.biomedcentral.com/1471-2474/13/241/prepub


Pre-operative decolonization therapy (DcTx) using chlorhexidine (CHG) body washes and/or intranasal mupirocin can reduce surgical site infections (SSI) but compliance is often suboptimal. The effectiveness of a novel approach to immediate pre-operative decolonization therapy using intranasal antimicrobial photodisinfection therapy (PDT) and CHG body wipes in reducing SSIs was assessed.To determine if immediate pre-operative decolonization using PDT and CHG body wipes reduced SSI rates.Between Sept 1, 2011 and Aug 31st 2012, 3068 elective cardiac, orthopedic, spine, vascular, thoracic and neurosurgery patients were treated with CHG wipes the night prior and day of surgery and received intranasal PDT in the preoperative waiting area. Weekend cases, procedures performed after the pre-operative dayshift, and emergency cases going directly to the operating room were not eligible. SSI surveillance remained unchanged from previous years and patients were followed for a minimum of three months. Results were compared to a historical control group consisting of 12,387 patients over four years and to a concurrent control group of 196 untreated patients.Staphylococcus aureus infection was higher in the concurrent untreated (61%= 11/18 infections) compared to the treated group (32%=16/50 infections). The reduction in SSIs compared to the historical rates resulted in a cost avoidance of approximately $1.2 Million (Can) and would have permitted approximately 140 additional surgeries to be performed.A significant reduction in the SSI rate was observed after the intervention [historical-control group 2.7% and treatment group 1.6% (p <0.0001 RR 1.0114)]. The risk of having a The combination of PDT and CHG wipes immediately pre-operatively reduces SSIs and is cost-effective.E. Bryce Grant/Research support from The Vancouver Hospital Foundation funded this project. Ondine Biomedical discounted the cost of PDT supplies and provided technical advice but had no role in data collection, analysis or interpretation of results, T. Wong Grant/Research support from The Vancouver Hospital Foundation funded this project. Ondine Biomedical discounted the cost of PDT supplies and provided technical advice but had no role in data collection, analysis or interpretation of results, D. Roscoe Grant/Research support from The Vancouver Hospital Foundation funded this project. Ondine Biomedical discounted the cost of PDT supplies and provided technical advice but had no role in data collection, analysis or interpretation of results, L. Forrester Grant/Research support from The Vancouver Hospital Foundation funded this project. Ondine Biomedical discounted the cost of PDT supplies and provided technical advice but had no role in data collection, analysis or interpretation of results, B. Masri Grant/Research support from The Vancouver Hospital Foundation funded this project. Ondine Biomedical discounted the cost of PDT supplies and provided technical advice but had no role in data collection, analysis or interpretation of results.


Clinical trials in chronic pain often collect information about interference with work as answers to component questions of commonly used questionnaires but these data are not normally analysed separately.We performed a meta-analysis of individual patient data from four large trials of pregabalin for fibromyalgia lasting 8-14 weeks. We analysed data on interference with work, inferred from answers to component questions of Fibromyalgia Impact Questionnaire (FIQ), Short Form 36 Health Survey, Sheehan Disability Scale, and Multidimensional Assessment of Fatigue, including "How many days in the past week did you miss work, including housework, because of fibromyalgia?" from FIQ. Analyses were performed according to randomised treatment group , pain improvement , and end of trial pain state .Comparing treatment group average outcomes revealed modest improvement over the duration of the trials, more so with active treatment than with placebo. For the 'work missed' question from FIQ the change for patients on placebo was from 2.2 (standard deviation [SD] 2.3) days of work lost per week at trial beginning to 1.9 (SD 2.1) days lost at trial end (p < 0.01). For patients on 600 mg pregabalin the change was from 2.1 (SD 2.2) days to 1.6 (SD 2.0) days (p < 0.001). However, the change in days of work lost was substantial in patients with a good pain response: from 2.0 (SD 2.2) days to 0.97 (SD 1.6) days (p < 0.0001) for those experiencing >/= 50% pain improvement and from 1.9 (SD 2.2) days to 0.73 (SD 1.4) days (p < 0.0001) for those achieving a low level of pain at trial end (<30 mm on the VAS). Patients achieving both >/= 50% pain improvement and a pain score <30 mm on the VAS had the largest improvement, from 2.0 (SD 2.2) days to 0.60 (SD 1.3) days (p < 0.0001). Analysing answers to the other questions yielded qualitatively similar results.Effective pain treatment goes along with benefit regarding work. A reduction in time off work >1 day per week can be achieved in patients with good pain responses. Fibromyalgia is a common chronic pain condition. It occurs in 1-2% of the population, more often in women than in men . ChronicIn clinical trials of treatments for chronic painful conditions - including trials in fibromyalgia - data on time off work and interference with work are typically collected as answers to component questions of commonly used questionnaires. Answers from these component questions are used to calculate overall scores of the questionnaires, but are not usually analysed separately and specifically with regard to work-related outcomes. Such an analysis - though not originally intended by the inventors of the questionnaires or the triallists who used them - nonetheless has the potential to provide useful insights into the outcomes associated with pain treatment: Do the patients with the greatest improvement in pain scores over the duration of the trial and those who have the lowest levels of pain at trial end also have the largest benefit with regard to work? How large is the benefit? Do patients with no or little pain improvement and high end of trial pain scores achieve any meaningful benefit regarding work?We have recently addressed the question whether benefit in chronic pain trials across different domains of life occurs in the same patients, using a large set of individual patient data from randomised controlled trials (RCTs) of pregabalin in fibromyalgia . We founWe analysed answers to work-related component questions from different questionnaires commonly used in chronic pain trials all addressing work but using different wording and assessment scales. Our aims were threefold: first, to illuminate the relationship between pain treatment, pain response, and work; second, to investigate the comparability of answers to work-related questions from different questionnaires; and, third, to provide a framework for future analyses of data on work-related outcomes collected in clinical trials in chronic painful conditions.We performed a meta-analysis of individual patient data from four large trials of pregabalin for fibromyalgia lasting 8-14 weeks, analysing data on interference with work, inferred from answers to component questions of Fibromyalgia Impact Questionnaire (FIQ), Short Form 36 Health Survey (SF-36), Sheehan Disability Scale (SDS), and Multidimensional Assessment of Fatigue (MAF), including "How many days in the past week did you miss work, including housework, because of fibromyalgia?" from FIQ. Analyses were performed according to randomised treatment group , pain improvement , and end of trial pain state .Pfizer Inc. provided Excel files containing individual patient data from four RCTs of pregabalin (Lyrica) in the treatment of fibromyalgia along with PDF files of the corresponding clinical trial reports. Pfizer study ID numbers of these trials and ClinicalTrials.gov identifier numbers (where available) were as follows:• 1008-105 • A0081056, NCT00645398 • A0081077, NCT00230776 • A0081100, NCT00333866 An enriched enrolment randomised withdrawal trial, the "FREEDOM trial" , was notPatients in the four included trials were at least 18 years old, fulfilling American College of Rheumatology classification criteria for fibromyalgia (1990 classification criteria) and with pain scores of ≥40 mm on the 100 mm VAS after stopping any relevant pain or sleep medication. Patients were randomised to receive pregabalin , or placebo, predominantly with a 2-week dose escalation phase followed by fixed dosing for up to 14 weeks of total trial duration. The minimum requirement for inclusion in this individual patient meta-analysis was that trials had to be both randomised and double blind.Trial and patient characteristics are detailed in Additional file We analysed individual patient data on pain scores and time off work or interference with work obtained at the beginning of the trials (baseline measurements) and at the end of trials. Data on time off work or interference with work were compared• according to randomised treatment group ,• according to pain improvement, as described by the comparison of baseline numerical pain rating scores  with end of trial numerical pain rating scores , and• according to pain state at end of trial, as assessed by the VAS pain score on a 0-100 mm scale.Not all questionnaires were used in all trials and not all patients had usable individual patient data available. Therefore the number of patients contributing to individual analyses differed. Numbers of patients contributing are given in Tables Cut-off levels for pain improvement and end of trial pain state were chosen with clinical relevance in mind and were based on published evidence. The Initiative on Methods, Measurement, and Pain Assessment in Clinical Trials (IMMPACT) defined benchmarks for interpreting change in chronic pain clinical trial outcome measures : a 'miniWe also analysed time off work and interference with work according to whether patients achieved the status of a 'state responder' , 'improvement responder' , 'double responder' (state and improvement responder), or 'non-responder' (neither state nor improvement responder).This approach was applied to the following five component questions from four commonly used questionnaires:• "How many days in the past week did you miss work, including housework, because of fibromyalgia?"  from the FIQ;• "When you worked, how much did pain or other fibromyalgia symptoms interfere with your ability to do your work, including housework?"  from the FIQ;• "During the past 4 weeks, how much did pain interfere with your normal work (including both work outside the home and housework)?"  from the SF-36;• "The symptoms have disrupted your work/school work"  from the SDS;• "In the past week, to what degree has fatigue interfered with your ability to work?"  from the MAF.Spreadsheet calculations from the individual patient data were performed independently of Pfizer by one of the authors: Jocelyn Paine from the commercial spreadsheet calculating and programming service 'Spreadsheet Factory' . The staBased on response data from the question "How many days in the past week did you miss work, including housework, because of fibromyalgia?" from the FIQ we compared placebo and pregabalin treatment arms of the trials Table . There wWhile the analysis of patients according to randomised treatment group (and irrespective of pain response) reveal only modest average improvements when trial beginning and end were compared, analysing patients according to pain improvement revealed substantial differences. Those patients with the largest pain improvements  also had the largest changes in days off work. Those with at least 50% pain improvement gained about one day of work per week  likewise revealed a close relationship between pain experience and time off work. While there was little difference in time off work in those with a final VAS pain state >50 mm, those with a pain state >30-50 mm benefited substantially, and patients with a final pain state of 0-30 mm benefited extensively, gaining about 1.3 days of work per week  revealed modest improvement when trial beginning and end were compared, somewhat more so in the pregabalin groups than with placebo (data not shown).Analyses of state and improvement responders likewise yielded qualitatively similar results. We investigated between-question similarity by calculating the percent improvement in answers to the different work-related questions, in each case comparing responses at trial beginning and end. We performed these analyses according to pain improvement over the duration of the trials Table  and accoPatients with an end of trial pain state of 30 mm or less on the 0-100 mm VAS had an improvement in the score for the FIQ questions about days of work missed and work interference of 61% and 56%, respectively. Those with a final VAS score >50 mm only had minimal improvement in days of work lost and work interference Table . Again, Analysis of data at the level of the individual patient can reveal insights over and above those that can be obtained from the analysis of group mean values but it is only possible when trial data are made available at the level of the individual patient. We had such data for pregabalin trials in fibromyalgia, but not for pregabalin in other painful conditions, nor for other drugs in fibromyalgia or other painful conditions. The availability of clinical trial data at the level of the individual patient is uncommon, especially where trials have consistently used several different assessment scales permitting analysis of the relationship between treatment success as measured by pain relief and work interference.This study demonstrated that most benefit regarding work in trials of pregabalin for fibromyalgia is obtained by patients who have large improvements in pain intensity, achieve a low level of pain after treatment, and especially if they achieve both of these outcomes. Comparing treatment groups irrespective of pain outcomes reveals a picture of only modest average benefit of active treatment when compared with placebo. However, substantial benefit in work-related outcomes can be demonstrated in those for whom treatment 'works' in the sense that it leads to a reduction in pain or a low end of trial pain state. Relationships between higher levels of pain and increased disability and interference with activities have been shown for a variety of conditions including cancer pain, phantom limb pain, back pain, and carpal tunnel syndrome -30, but The point that fibromyalgia leads to substantial interference with work is well worth making. The status of fibromyalgia as a valid disease entity, let alone one with a substantial impact on a variety of domains of life, has long been in question because a clear physical correlate of the disease could not be demonstrated. Not surprisingly, in the face of such scepticism the diagnosis of fibromyalgia is often delayed . RecentlThe IMMPACT group suggested that 50% improvement in pain intensity is 'substantial improvement' . Other eOur analysis provides further evidence that benefit due to treatment of fibromyalgia with pregabalin across different domains of life occurs largely in the same patients, as we previously suggested . Those pWe found that data from several questions about time off work and interference with work with somewhat different wording and from different questionnaires yielded overall similar results, though when expressed as percent improvement in scores  is present. We had no objective records of time at work or time off work on which to base our analysis; nor did we have a detailed description of the type of occupation. This would have been interesting because different kinds of occupation may be differently affected by pain and its treatment. Moreover, we only used data from four trials of pregabalin in fibromyalgia where we had individual data available; other chronic pain conditions and treatments might produce different results.These limitations determine the agenda for future research: The first step would be a repetition of this type of analysis for different work-related questions, different treatments and different chronic pain conditions to determine whether or not our findings are general. Because data on time off work and interference with work are commonly collected in chronic pain trials, this is primarily a question of obtaining access to the data and performing the analyses. The second step will be more difficult: to collect more detailed information on occupation and objective data on time off work as part of clinical trials in chronic pain. We hope that raising the awareness of these issues will lead to such data being collected in chronic pain trials in the future.This meta-analysis of individual patient data from four trials of pregabalin for fibromyalgia demonstrates that effective pain treatment, described in terms of pain improvement over the course of the trials and end of trial pain state, is linked with benefit regarding work. A reduction in time off work of more than one day per week can be achieved in patients with good pain responses. Analysing answers to work-related component questions from different questionnaires yields qualitatively similar results.FIQ: Fibromyalgia Impact Questionnaire; IMMPACT: Initiative on Methods, Measurement, and Pain Assessment in Clinical Trials; MAF: Multidimensional Assessment of Fatigue; NS: no significant difference; RCT: randomised controlled trial; SD: standard deviation; SDS: Sheehan Disability Scale; SF-36: Short Form 36 Health Survey; VAS: visual analogue scaleSS received research support and grants from charities, Bandolier, Reckitt Benckiser, and Georg-August-University Göttingen and received lecture fees from University Children's Hospital Zurich and Oxford Medical Knowledge. RAM received lecture fees from Merck, Pfizer, Menarini, Lundbeck, AstraZeneca; served as a consultant for Merck, Pfizer, Eli Lilly, Flynn, Futura, Altana, Fujisawa, GSK, Shire, Sanofi-Aventis, Grünenthal, Organon, ZARS; received research grants from Merck, Pfizer, Abbott, AstraZeneca, Menarini, GSK, Aspreva, Janssen-Cilag. CJP received lecture fees from Merck, Gilead and Lundbeck in the past year, served as a consultant for Merck, Pfizer and Sanofi-Aventis in the past year and received a departmental grant from Napp in the past year. SD received research support from UK government and charities. HJM received lecture or consultancy fees in the past year from Menarini, Esteve, Grünenthal, Pfizer, Reckitt Benckiser, IMS and Archimedes.SS and RAM were involved with the original concept, planning the study, writing it, analysis, and preparing a manuscript; JP performed the calculation; SD, CJP, EH, and HJM. were involved with planning, and writing. All authors read and approved the final manuscript.The pre-publication history for this paper can be accessed here:http://www.biomedcentral.com/1471-2474/12/125/prepubStudy and patient characteristics. The studies are identified by their Pfizer study ID numbers, the ClinicalTrials.gov identifier numbers (where available), and references to publications.Click here for file


The increasing number of patients with chronic pain in Japan has become a major issue in terms of the patient's quality of life, medical costs, and related social problems. Pain is a multi-dimensional experience with physiological, affective, cognitive, behavioral and social components, and recommended to be managed via a combination of bio-psycho-social aspects. However, a biomedical approach is still the dominant method of pain treatment in Japan. The current study aimed to evaluate comprehensive psychological functions and processes in Japanese chronic pain patients.The Rorschach Comprehensive System was administered to 49 in-patients with non-malignant chronic pain. Major variables and frequencies from the test were then compared to normative data from non-patient Japanese adults by way of the t-test and chi-square test.Patients exhibited high levels of emotional distress with a sense of helplessness with regard to situational stress, confusion, and ambivalent feelings. These emotions were managed by the patients in an inappropriate manner. Cognitive functions resulted in moderate dysfunction in all stages. Information processing tended to focus upon minute features in an inflexible manner. Mediational dysfunction was likely to occur with unstable affective conditions. Ideation was marked by pessimistic and less effective thinking. Since patients exhibited negative self-perception, their interpersonal relationship skills tended to be ineffective. Originally, our patients displayed average psychological resources for control, stress tolerance, and social skills for interpersonal relationships. However, patient coping styles were either situation- or emotion-dependent, and patients were more likely to exhibit emotional instability influenced by external stimuli, resulting in increased vulnerability to pain.Data gathered from the Rorschach test suggested psychological approaches to support chronic pain patients that are likely to be highly beneficial, and we thus recommend their incorporation into the course of current pain treatments. The number of patients with chronic pain in Japan is estimated to be approximately 17 million ,3.Pain of any kind can be a strong impetus for patients to seek medical care as they assume that pain indicates a serious medical matter. Pain is defined by the International Association for the Study of Pain (IASP) as "an unpleasant sensory and emotional experience associated with actual or potential tissue damage, or described in terms of such damage" and regarded as chronic when non-malignant pain persists for more than six months . EmotionMost of our chronic pain patients appeared to be exhausted both physically and psychologically when referred to our Department of Psychosomatic Medicine. Patients often complained of dissatisfaction with previous treatments and distrust of medical professionals. Consequently, our physicians often experienced difficulty in establishing therapeutic relationships with these patients at the time of admission. Kenny suggests that a fundamentally complicating factor between a patient and his/her physician may originate from "struggles for legitimating the cause of pain", as either biogenic or psychogenic . This isPsychological aspects of chronic pain patients have been the subject of many studies, which have revealed important psychological constructs that can prolong or exacerbate pain, such as pain catastrophizing , fear avPsychological measures of these studies were obtained by self-reporting questionnaires which focused mainly upon the assessment of psychopathology. However, findings often appeared to be due to the presence of chronic pain and related symptoms rather than psychopathology, and did not indicate the original psychological resources of the patients concerned. In consideration of the complexities of pain experiences, the Rorschach Comprehensive System (CS) could be used to provide multi-dimensional psychological aspects of chronic pain patients. This system investigates both original psychological resources and processes that generate symptoms and/or behaviors as they are similar to those in producing Rorschach responses. Furthermore, respondents' efforts to minimize problems might not bias the results as they are rarely aware of the type of interpretation to be made for their responses . Using tThe Rorschach CS has never been fully explored in Japanese patients suffering from chronic pain, and this study therefore aimed to investigate comprehensive psychological characteristics of Japanese patients with chronic pain.One hundred and three (103) in-patients reporting non-malignant pain for more than six months were admitted to the Department of Psychosomatic Medicine in Kansai Medical University Hospital between January 2006 and June 2008. Twenty-three patients (22%) who were under 20 or over 70 years of age were excluded in order to compare the Rorschach data against control non-patient Japanese adults within the same age range. Nineteen patients (18%) could not be contacted upon their admission for logistical reasons, and ten (10%) were excluded due to physical conditions or as a result of decisions made by their attending physicians. Two patients (2%) refused to participate. After written informed consent had been obtained from the remaining forty nine (49) patients, the Rorschach CS was administered by the first author, a clinical psychologist. One patient was subsequently eliminated due to an insufficient number of responses, as normal protocol tests with less than 14 responses are considered invalid in the CS system , leavingTable The Rorschach Comprehensive System (CS) has standard administration rules and is the most commonly-used scoring system in the world. It has good inter-rater and test-retest reliability with good statistical construct validity ,25. In tThe responses of our chronic pain patients were scored by the first author, a clinical psychologist. Scorings were reviewed by a second clinical psychologist affiliated with a different department and finalized after discrepancies had been discussed. Further consultations were made with a Rorschach expert to finalize data when agreement was not reached between the two local psychologists. Both clinical psychologists were trained in the administration and scoring of the Rorschach CS and have extensive experience with this system.Means and frequency data of all major variables arising from the Rorschach CS were compared between chronic pain patients (hereafter referred to as 'CP patients') and non-patient adults (hereafter referred to as the 'NA group'). The latter group consisted of 200 males 35.26 ± 12.28) and 200 females (35.92 ± 12.02) with the mean age of 35.59 (±12.84) [ ± 12.28 All procedures were submitted and approved by the Ethical Committee of Kansai Medical University Hospital.Tables Here, we examined the capacity to make decisions and implement specific behaviors that meet the demands of situations which involve the use of resources, stimulus demands, and stress tolerance. The Adjusted D score , the D score , and the Experience Actual score  in CP patients were within the expected range, and no significant inter-group differences were apparent. The Experienced Stimulation score  of CP patients was within the expected range, but was significantly higher than that of the NA group . Fewer CP patients exhibited the introversive coping style, implying that fewer CP patients reasoned things through while keeping emotions aside before making decisions or problem-solving. Half of CP patients and half of the NA group were classified as exhibiting the ambitent style, which is an inconsistent or flexible way of using thoughts and emotions according to situations. More CP patients exhibited the extratensive style, suggesting that they tend to invest more of their feelings into decision-making and/or problem-solving processes and are more likely to use interactions with their environment as a source of information and/or gratification.Variables relating to affect examine the role of emotions in the psychological function and organization of the person. The frequency of a positive Suicide Constellation  in CP patients was significantly higher (6%) than the NA group , such as self-destructive thoughts (S-CON), depressive mood (DEPI > 4) and a sense of helplessness due to situational stress (SumY). These patients did not use the tactic of psychologically ignoring the complexity and/or ambiguity of a field (L), and their psychological function and processing seemed more complicated and confused by ambivalent feelings . Their modulation of emotional discharge was likely to be unstable; in other words, CP patients exhibited a tendency to either excessively internalize their feelings (SumC'), or discharge them expulsively in a more uncontrolled manner .Here, we examined three aspects of cognitive function, or a cognitive triad, i.e. (i) information processing; (ii) cognitive mediation; and (iii) ideation, thinking process leading to some form of mental conceptualization of translated information.Variables of information processing assess mental procedures entailed in the input of information. There were no significant differences in the total number of responses (R) to 10 inkblots between CP patients (22.02 ± 8.45) and the NA group (23.51 ± 6.9), or when considering the Whole response  and the Hypervigilance Index . Common Detail response  was significantly lower in CP patients than the NA group ; instead, they focus more on minute or unusual features within a new field of information (Dd). Scanning efficiency and the quality of processing activity of CP patients appears more than adequate compared to the NA group (Zd), but more patients in the CP patient group exhibited a little difficulty in shifting their attention (PSV).Variables concerning cognitive mediation assess mental operations that translate or identify inputted information. The Perceptual-Thinking Index positive score  was significantly greater in CP patients than the NA group . The probability of fewer conventional responses occurring in simple and/or precisely-defined situations with CP patients was low , even if problems were observed (X + %). However, CP patients exhibited a moderate elevation in the incidence of mediational dysfunction , when associated directly to unstable affective conditions, particularly relating to possible feelings of negativity or anger (S-).Variables concerning ideation assess conceptualization of translated inputs. Morbid content  in CP patients showed a slightly higher incidence from the expected value, and was significantly greater than that in the NA group , but that they did not defensively substitute fantasy for reason in stressful situations (Mp < Ma). Furthermore, CP patients did not exhibit a conceptual failure with discrimination and/or the inability to use concrete reasoning (INCOM), but they did show cognitive mishaps (Wsum6) with regard to: 1) use of distorted language and/or idiosyncratic modes of expression (DV); 2) indecisiveness and/or a defensive attempt to detach themselves from the task at hand (DR); and/or 3) strained effort or use of unconventional reasoning to justify an answer (ALOG).Variables on self-perception assess self-image and self-involvement. Vista response  showed a slightly higher incidence from the expected value, and was significantly greater in CP patients than the NA group , and that their self-image is likely to be negative (MOR). However, this perception of themselves or others might not always be based on reality (Pure H = 0).Interpersonal perception and behavior data assess how a person perceives others, and how they will behave in various interpersonal situations. The frequency of positive Coping Deficit Index  showed no inter-group difference between CP patients and the NA group. Texture response  was significantly lower in CP patients than the NA group . However, they are generally not open to close emotional interactions, and can be apprehensive (T). They tended to perceive interpersonal exchanges as aggressive or competitive (AG) with less reality-based evidence (PureH = 0), and were warded off challenges (PER), which then led to less effective and/or maladaptive interpersonal behavior .When pain becomes persistent, it often accompanies various types of aversive emotional and cognitive effects, which are likely to lead to deterioration of private and social lives. Rudy et al suggest that the characterization of pain as only a sensory discomfort of the pain-specific part of the body is not sufficient without inclusive perspective of emotional states and accompanying thoughts as the central role for clinically important pain control strategies . The purAffective states of CP patients revealed that they experienced highly unusual distress or discomfort , including situational stress-related psychological helplessness (Y), self-destructive preoccupation (S-CON) and implicit depressive mood (DEPI). When we consider the IASP definition of pain, our present findings demonstrate that the pain experience is accompanied by various types of emotional distress in addition to pain specific discomfort . WhetherPerception of control has an important relationship with affective distress . PatientCausal relationships between chronic pain and depression have been the subject of much debate. None of CP patients in the present study met the criteria for a major depressive episode, although DEPI positive frequency was significant compared to the NA group. Rudy et al found that when patients perceived a persistent pain as far beyond control, then they were more likely to increase affective distress, and proposed that the psychological mediators might be in the development of depression secondary to chronic pain . A furthAs for emotional discharge, our CP patients showed excessive internalization or inhibition of emotions (C'), and were expressive in an uncontrolled manner . Their emotions were not well controlled and expressed in extreme manners. This could be explained by the emotional states of CP patients showing significant low L, high Blends and Col-Shading, indicating that patients were suffering psychological complexity such as confusion and ambivalent feelings that they were not able to articulate properly. Also, emotions involving diffuse bodily states are often chaotic and change rapidly such that the language available to describe emotional states tends to be vague or amorphous . The higWith regards to alexithymia, Acklin and Bernat proposed the trait for this condition in patients with low back pain based upon results from ambitent coping style and seven Rorschach constrictedness variables, including low R, low M, low WsumC, low FC, low Blends, high Lambda, and low EA . The resThree cognitive functions, the 'Cognitive Triad' have been defined as: 1) information processing, 2) cognitive mediation, and 3) ideation. These are collective functions and reflect a continuous or circular process to form the basis of all deliberate and/or meaningful behaviors .Information processing results demonstrated that our CP patients actively processed information effectively (D), and their scanning efficiency (Zd) and quality of processing activities (DQ +) were usually more adequate than the NA group. However, CP patients were likely to focus more upon minute or unusual features of a new field of information (Dd), and had a tendency to be inflexible in shifting their attention (PSV). This is reminiscent of the features of chronic pain patients who tend to be attentive to their pain and their complaints sometimes are felt as obstinate. Their focus on pain might lead to increased pain stimuli. Tracy et al reported that increased attention to pain increased pain intensity, whereas significant pain reduction was observed during distraction .Cognitive mediations evaluate how the inputted image is identified or translated, focusing the extent to which the person acknowledges external reality when making decisions, as opposed to being influenced by psychological status. Cognitive mediations of our CP patients were less appropriate  than the NA group, but the probability of a less conventional response  occurring was minimal in simple and/or precisely defined situations. However, their mediation showed moderate dysfunction  with deviations from expected values. The significant incidence of these minus responses in CP patients indicated that some of their personal aspects caused the stimulus field to be disregarded and replaced by internal aspects projected into the response. Minus responses could be provoked by many reasons such as ideational sets, preoccupations and emotional elements, and all kinds of emotions can interfere with mediation . As indiIdeation focuses upon the characteristics of thinking, the quality and clarity of ideation, the frequency with which associated aspects manifest, and the manner in which it is used. Results from our CP patients suggested difficulties in conceptual thinking or an issue of ideational clarity as shown in the highly significant values of MOR and WSum6. MOR, a moderate pessimistic set, suggested that CP patients anticipate gloomy outcomes for their efforts, and that this negative perception is likely to be reinforced and interact with a sense of helplessness, as indicated by emotional issues. In addition, when the highly significant value of ALOG, which represents a tendency of unconventional or strained reasoning to justify the answer, is applied to pain and pain-related situations, it is likely to promote a type of catastrophic pain thinking and therefore contribute to a more intense pain experience and increased emotional distress . This maIn a medical setting, the National Institute for Japanese Language found that most Japanese patients had the experience of being puzzled by unfamiliar words in conversations with physicians . In doctFirst, it is useful to point out that our CDI negative results Table  suggest Our self-perception data contribute to our understanding of interpersonal perceptions and behaviors. Significantly low T and high PER values suggest that CP patients tended to be overly concerned with personal space and that they were much more cautious or defensive about creating or maintaining close emotional ties with others. Significantly high AG values showed that CP patients tended to perceive interpersonal exchanges as aggressive or competitive without reality-based evidence. Thus, their interpersonal behavior might not always be effective and adaptive. These findings indicate that CP patients appeared to lack emotionally close relationships and to be isolated. This situation is likely to make chronic pain patients focus more upon pain and their misery, as Turk and Flor found in many chronic pain patients whose preoccupation with their own bodies would lead to increased awareness and overestimation of sensory information .Rorschach CS data compiled from our CP patients were examined in terms of emotional, cognitive and interpersonal aspects, as well as their original psychological resources. Findings suggest that pain and pain-related situations were mostly viewed as major stressors in patients' lives that triggered a certain degree of emotional distress, cognitive dysfunction and maladaptive interpersonal relationships. Our results did not indicate psychopathology, a finding consistent with previous studies by Gatchel & Okifuji and Maruta ,42. PhysOur present study has several limitations. The chronic pain patients investigated in this study represented one extreme of the total chronic pain patient population and should not be viewed as being representative of the Japanese chronic pain population in general. Our patients had a long history of pain. Consequently, Rorschach findings may be related to other dimensions of psychological adaptation to disease and health-related quality of life. Our study involved a female to male ratio of 2:1 and therefore psychological characteristics might be more reflective of female patients. Further studies should be designed to take this into account. In the present study, comparisons were made to normative data from non-patient Japanese adults. Future investigations have already been implemented using control data. Other types of psychological assessment measures specific to pain could be added as a test battery in order to further our understanding of the more specific features of patients with chronic pain. Interactions with patients and medical professionals were not examined in this study and future research will be needed to help the patient-doctor relationship become more productive and therapeutic.A comprehensive series of psychological characteristics determined from Japanese patients with non-malignant chronic pain were examined and compared to non-patient Japanese adults using the Rorschach CS. Results showed that these patients demonstrated high emotional distress, moderate cognitive dysfunction, and ineffective interpersonal interactions. This was in spite of the fact that they originally exhibited adequate psychological resources with capacities for control, stress tolerance and adequate interpersonal skills. In consideration with the multi-dimensional experience of pain, we recommend that medical professionals incorporate some degree of psychological intervention into conventional pain treatment regimens.The authors declare that they have no competing interests.KY conceptualized and designed the study, collected and analyzed the data, interpreted the results, and drafted the manuscript. KK and MF helped in drafting the manuscript. MY helped in the Rorschach analysis while AT and IB helped with the statistical analysis. HM, YM, TA and YN provided overall advice. All authors read and approved the final manuscript.


Epicrania fugax (EF) is a novel syndrome, described as a paroxysmal and brief head pain, starting in posterior cranial regions and rapidly spreading forward ipsilateral eye, nose or forehead. Two patients with comparable clinical features stemming from frontal scalp to ipsilateral posterior regions have been recently described and proposed as backward radiation epicrania fugax (BREF). We report a new series of nine BREF and compare their clinical characteristics with 18 forward radiation EF (FREF). Since first description of BREF in February 2010 we have assessed nine patients  with this clinical picture at an outpatient headache office in a Tertiary Hospital. Comparison is established with 18 FREF patients , attended since the publication of first series of EF in March 2008. We found no differences between BREF and FREF, respectively, in age at onset (43.4 ± 13.1 vs. 42.5 ± 17.7 years), female/male ratio (5/4 vs. 12/6), pain intensity , duration (7.1 ± 4.9 vs. 5.7 ± 4.3 s) and frequency of episodes per day (7 ± 8.4 vs. 9.9 ± 15.4). Patients in BREF group presented less frequently interictal pain in stemming point (22.2 vs. 55.5%) and accompanying autonomic signs (33.3 vs. 55.5%), but without statistical significance in both the cases. This series reinforces the proposal of EF as a new headache variant or a new headache syndrome. Clinical picture of brief pain paroxysms starting in the anterior scalp and radiating backwards does not fit known headaches or neuralgias and might correspond to a reverse variant of EF, clinical characteristics of which are comparable to FREF. Epicrania fugax (EF) is a novel syndrome first described by Pareja et al.  in 2008 To this first series, 15 new patients with the same clinical features have been added, so reinforcing the proposal of EF as a new headache variant or a new headache syndrome –4. RecenSince the first description of BREF in February 2010, we made, in an outpatient headache clinic located in a Tertiary Hospital, a prospective search of the patients complaining of brief pain paroxysms running front to back, from anterior to posterior cephalic regions. As we searched for a novel headache syndrome, we took special care not to induce false answers during the interviews.A detailed history was obtained in all the cases, including precipitant event and the coexistence of other types of headache. The characteristics of pain paroxysms were carefully evaluated, including temporal features (duration and frequency) and spatial features . Other characteristics such as pain quality, pain intensity , or pain accompaniments, especially autonomic signs have been included. The presence of any triggers or interictal pain was also evaluated. Subsequently, a complete physical and neurological examination was performed, including inspection, palpation and sensory examination of the stemming area, as well as palpation of the supraorbital, infraorbital, supratrochlear, minor occipital and greater occipital nerves. Computed tomography or magnetic resonance imaging of the head, and routine blood work-up with erythrocyte sedimentation rate and immunological screening were carried out in all the cases.We also made a prospective search of patients with a clinical picture from March 2008, which would be comprised under the headings or epicrania fugax with forward radiation, as was described by Pareja at al . We regit test was employed in the quantitative variables.Statistical analysis was performed with SPSS 18.0 software. Level of significance was established at 5%. We compared the characteristics of both groups with a Chi-square test and also Fisher’s exact test, if necessary. Two-tailed Student Through a one-year period, we assessed nine patients , with pain paroxysms comparable to BREF. Mean age at onset was 43.4 ± 13.1 years range 26–62). Demographic and clinical features of these nine patients are shown in Table 6–62. DemWe found no differences between BREF and FREF, respectively, in age at onset (43.4 ± 13.1 vs. 42.5 ± 17.7 years), and female/male ratio (5/4 vs. 12/6). A complete examination of stemming points did not reveal trophic changes in any of the patients and sensory disturbances were appreciated in 8 out of 12 patients, who suffered interictal pain. Palpation of pericranial nerves did not detect abnormal findings, and laboratory tests and imaging studies were also normal in all the cases.n = 5), forehead (n = 1) or frontal region (n = 3), and inmediately spread backwards along a linear trajectory to occipital (n = 7) or parietal (n = 2) scalp. In two of the patients, there was an interictal pain in stemming point located in a circumscribed area, resembling nummular headache. In one of them exam disclosed a focal sensitive dysfunction. Paroxysms were described as stabbing in most of the patients (n = 6), or as electric, burning or pressing (1 patient each).Pain paroxysms were strictly unilateral in all BREF patients (in five cases on the left and in four on the right). Four cases described a history of migraine and one of tension-type headache, but EF was considered as quite different from the other headaches. Pain started in eye , pain intensity in a 0–10 visual analogical scale (6.9 ± 2.1 vs. 6.8 ± 2.1), frequency of episodes per day (7 ± 8.4 vs. 9.9 ± 15.4), presence of triggers (22.2 vs. 22.2%) and prophylactic treatment requirement (77.7 vs. 66.6%).Patients in BREF group presented less frequently interictal pain in stemming point (22.2 vs. 55.5%) and accompanying autonomic signs (33.3 vs. 55.5%), but in both the cases without statistical significance.In 2008, Pareja et al.  describeRegarding EF, there are several entities to which differential diagnosis have to be considered. For instances, there are similarities between EF and primary stabbing headache (PSH). PSH is a primary headache syndrome, with a female preponderance, characterized by short (3 s or less) stabbing pain paroxysms in a localized area that start and end in the same place , 11. FreNummular headache (NH) resembles EF in the presence of a focal painful area. Pain in NH is typically continuous and, when paroxysms are superimposed, they begin and end in situ , 13. EigLacrimation, rhinorrhoea and itching eye are autonomic signs that appears in some of our patients. These signs are typical of other headache syndromes such as SUNCT  or SUNA  . These hUnlike SUNCT, SUNA  can be dThe pathogenesis of EF is uncertain. Origin of this pain is probably peripheral according to the existence of a stemming or trigger zone in a focal area, and the stabbing or electric character of the pain. Paroxysms of pain can originate in the terminal branches of supraorbital nerve (SON) or greater occipital nerve (GON), and eventually extend to the peripheral fibers or branches. It has been proposed that the spreading of the pain is due to the electric transmission or paracrine diffusion of chemical mediators. Central mechanisms in which trigeminal afferents are implicated cannot be excluded, mainly in those patients presenting with autonomic signs .We report nine patients with the same features described for EF, except the direction of radiation. When we compare them with a group of patients fulfilling the characteristics of EF, we do not find differences between both the groups.Our report reinforces EF as an independent headache syndrome and proposes BREF as a not infrequent variant of EF. Their features do not fit other acknowledged headaches or neuralgias. Another option is to in considered BREF and FREF as the same entity with the different presentations. Further observations are requiered for a definitive characterization of these headaches.


Neuropathic pain has been little studied in leprosy. We assessed the prevalence and clinical characteristics of neuropathic pain and the validity of the Douleur Neuropathique 4 questionnaire as a screening tool for neuropathic pain in patients with treated leprosy. The association of neuropathic pain with psychological morbidity was also evaluated.Adult patients who had completed multi-drug therapy for leprosy were recruited from several Bombay Leprosy Project clinics. Clinical neurological examination, assessment of leprosy affected skin and nerves and pain evaluation were performed for all patients. Patients completed the Douleur Neuropathique 4 and the 12-item General Health Questionnaire to identify neuropathic pain and psychological morbidity.One hundred and one patients were recruited, and 22 (21.8%) had neuropathic pain. The main sensory symptoms were numbness (86.4%), tingling (68.2%), hypoesthesia to touch (81.2%) and pinprick (72.7%). Neuropathic pain was associated with nerve enlargement and tenderness, painful skin lesions and with psychological morbidity. The Douleur Neuropathique 4 had a sensitivity of 100% and specificity of 92% in diagnosing neuropathic pain. The Douleur Neuropathique 4 is a simple tool for the screening of neuropathic pain in leprosy patients. Psychological morbidity was detected in 15% of the patients and 41% of the patients with neuropathic pain had psychological morbidity. Neuropathic pain has only recently been recognised as a complication of leprosy. We assessed 101 treated leprosy patients in Mumbai and found that 22 of them had neuropathic pain. The pain occurred as numbness 86%, tingling 68%, and decreased sensation to light touch 81%. This pain was significantly associated with nerve enlargement and tenderness, which suggests that ongoing inflammation may be important in causation. A questionnaire-based screening tool (Douleur Neuropathique 4) for detecting neuropathic pain has been developed and validated in other patients groups. We are the first group to have used the DN4 as a screening tool in leprosy patients and found that it worked well, detecting 78% of patients with no inappropriate diagnoses. There is also an increasing recognition that leprosy is associated with psychological morbidity. Neuropathic pain is also associated with psychological morbidity. We also assessed psychological morbidity using the 12-item General Health Questionnaire and found that neuropathic pain and psychological morbidity are associated with leprosy patients. Leprosy patients with neuropathic pain thus have a double hit for psychological morbidity. Clinicians looking after leprosy patients should warn their patients about neuropathic pain and assess their patients for psychological morbidity. Mycobacterium leprae that principally affects skin and peripheral nerves.M.leprae infection is treated with multi-drug therapy (MDT) and all patients receive either dual or triple drug therapy for up to 12 months. MDT is highly effective with a relapse rate of 1%. New nerve damage is treated with steroid therapy, but only about 50% of patients will have improvement in nerve function after a course of steroid treatment.Leprosy is a chronic granulomatous disease caused by Neuropathic pain is defined as “pain arising as a direct consequence of a lesion or disease affecting the nervous system”.Several diagnostic questionnaires have been developed to alert the clinician about the possibility of neuropathic pain, for example the Douleur Neuropathique 4 (DN4). The DN4 consists of seven items related to sensory descriptors and three related to signs which require a simple clinical examination.Little is known about neuropathic pain in leprosy patients. 26.4% of 358 newly presenting leprosy patients from a referral centre in Brazil had neuropathic pain.The clinical presentation of neuropathic pain in leprosy patients can be continuous or intermittent and occur at a single or multiple locations. Studies in India and Brazil found most patients with neuropathic pain had a “glove and stocking” symptom distribution, characteristic of polyneuropathy Several studies have shown increased prevalence of psychological morbidity in patients with leprosy. In some series, up to 65% of patients have psychological morbidity, depression being the most common.Non-psychotic mental disorders are defined in ICD-9 as “disorders in which the symptoms are distressing to the individual and recognized by him or her as being unacceptable”.This cross-sectional study was designed to assess the prevalence and characteristics of neuropathic pain in leprosy patients who have completed MDT. From previous studies Between July and August 2008, we enrolled 101 patients  from Bombay Leprosy Project clinics in the state of Maharashtra, India. Every patient (estimate n = 150) over the age of 16 who attended the clinics during the study period and had taken a full course of MDT was invited to participate. We did not collect reasons for non participation in the study as we should have done. This sample size was used because we estimated that we would detect about 20 patients with neuropathic pain.Leprosy was diagnosed when a patient had one of the following: skin lesions typical for leprosy; and/or thickened peripheral nerves; and/or acid fast bacilli on slit skin smears.Patients were defined as having neuropathic pain if distribution of pain was neuroanatomically plausible, confirmatory tests of neurological examination demonstrated positive or negative sensory signs confined to the innervation territory of the affected peripheral nerves, and pain was causally associated with having had leprosy.All patients were given a blank body chart  and askeNerve enlargement and tenderness was clinically evaluated by palpation of the main peripheral nerves , and defined as present or absent. Motor function was tested in the following nerves by assessing the muscle they supply: facial nerve (orbicularis oculi) ulnar nerve (abductor digiti minimi), median nerve (opponens pollicis) and common peroneal nerve . Sensory testing was done using a series of Semmes-Weinstein monofilaments (MF) (0.05 gm / 0.2 gm / 2 gm / 4 gm / 10 gm / 300 gm) to assess punctate static light touch perception in skin areas supplied by the ulnar, median and posterior tibial nerves.The WHO disability criteria, which has three levels, 0, 1 and 2, was used to document disability. Zero is scored when no disability is present, 1 when loss of sensation in hand or foot is present, and 2 when there is visible damage or disability including deformity, lagophthalmos or hand or foot ulcer.Both DN4 and GHQ-12 questionnaires were completed by the patient, with the clinician asking the questions since many patients were not functionally literate. When completing the DN4 questionnaire, if the patient had any of the symptoms, the area in which s/he had it was recorded beside each symptom. In these cases a clinical assessment of the area was undertaken, evaluating ‘hypoesthesia to touch’ by applying light touch with finger on the painful area and a non-painful area simultaneously, and ‘hypoesthesia to pinprick’ using the 300 g MF. Dynamic mechanical allodynia was evaluated using a brush on the painful area and patients responded Yes/No to the evoking of pain.For the GHQ-12, the patients were asked how they had felt during the past four weeks. If they had any symptoms, they were asked what cause they attributed to them. Interpretation of the answers is based on a four point response scale scored using a bimodal method . A score of four or more indicates the presence of a disorder, without diagnosing the exact pathology.Ethical approval was received from the London School of Hygiene and Tropical Medicine Ethics Committee prior to commencing the study. Ethical approval in India was received from the Bombay Leprosy Project Managing Committee.On recruitment, patients were given an explanation of the study, which was translated to Hindi or Marathi when needed before being invited to sign the consent form which was also in Hindi and Marathi. No patient was paid to participate in the study.A database was created using a Microsoft Excel spreadsheet, and analysed using Stata 10.1. A χ2 test was then used comparing all the variables to the outcome variables neuropathic pain, psychological morbidity, and presence of disability. For those variables with a significant p value a Mantel-Haenszel test was performed . MissingOne hundred and one patients were recruited , age range 17 to 89 years , of whom 22 (21.8%) had neuropathic pain. Ninety four patients (93%) had MB leprosy, and 7 (7%) had PB leprosy. Most patients (73%) had been diagnosed and treated for leprosy between 2001 and 2007; 20 between 1991 and 2000. During the period of recruitment about 150 patients were reviewed from urban and rural areas in the Bombay Leprosy Project clinics.Sixty nine patients (68.3%) had ongoing skin involvement with patches, nodules, ulcers or infiltration. Twenty four (23.8%) had painful skin lesions, of whom 9 (37.5%) had neuropathic pain. Forty six patients (45.5%) had nerve enlargement and 19 (18.8%) had nerve tenderness. Nerve enlargement was present in one nerve only in 14 patients (30.4%) and in multiple nerves for 32 (69.6%). Nerve enlargement was found most often in the ulnar nerve (65.22%), then the lateral popliteal (43.5%), posterior tibial (39.1%) and greater auricular (37.0%) nerves. Nerve tenderness was most commonly elicited in the ulnar nerve (68.4%), followed by the posterior tibial (57.9%), lateral popliteal (31.6%) and great auricular (15.8%) nerves.Ulnar nerve motor impairment was detected in 35 patients (34.7%). Combining motor and sensory testing, 65 patients had ulnar nerve impairment (64.4%) and 42 (41.6%) median nerve impairment. Seventy patients (69.3%) had plantar sensory impairment. Sensory testing detected impairment in the areas supplied by the lateral and medial plantar (69.3%), ulnar (45.5%), median (38.6%) and trigeminal (6.9%) nerves.Twenty two patients had neuropathic pain (21.8%) by the clinical definition, and Patients described sensory symptoms as numbness (19), tingling (15), burning sensation (13), electric shocks (11), pins and needles (10), painful cold (6) and three had itching and these symptoms overlapped in individual patients. Eighteen patients had hypoesthesia to touch in the painful area, 16 had hypoesthesia to pinprick, and one had allodynia.Twenty eight (27.7%) patients scored 4 or more on the DN4 questionnaire whilst 22 had neuropathic pain by the clinical definition. None of the patients clinically diagnosed with neuropathic pain scored less than 4 on the DN4. These six patients experienced some of the symptoms listed in the questionnaire occasionally in a certain area, but without pain or discomfort. One patient had pain with no anatomical plausibility. In this group the DN4 used for screening for neuropathic pain had a sensitivity of 78.6% and a specificity of 100%.Fifteen (14.9%) patients had psychological morbidity, mainly anxiety, mild or incipient depression, which they associated with having leprosy. Forty one percent of the patients with neuropathic pain had psychological morbidity. Some patients who scored less than 4 on the GHQ-12 explained that although they had some symptoms, such as lack of sleep or increased strain, they felt that these were not associated with their leprosy.Forty four patients (43.6%) had disability, eight had grade 1 (7.9%), and 36 grade 2 (35.6%). Of the 22 patients with neuropathic pain, 11 (50%) had disability grade 0, five had grade 1 (22.7%) and six grade 2 (27.3%).Neuropathic pain is significantly associated with psychological morbidity (p = 0.0001), nerve enlargement (p = 0.016), nerve tenderness (p = 0.0003), trigeminal nerve impairment (p = 0.0194), and painful skin patches (p = 0.0335) . No signThe study found a high prevalence of neuropathic pain (21.8%) among patients with treated leprosy at a referral centre in India. Neuropathic pain was associated with nerve enlargement and tenderness, and painful skin patches. Psychological morbidity was also significantly associated with neuropathic pain. In all patients, the diagnosis of definite neuropathic pain could be made because they had an established diagnosis of leprosy, and also positive and negative sensory signs on clinical neurologic examination correlating with the peripheral nerves that are affected in leprosy.The prevalence of neuropathic pain in treated leprosy patients was higher than expected from clinical practice, but similar to that found in patients with diabetic neuropathy in India (26.1%).Our study design, a cross sectional prevalence study, means that the patients in this study are typical of patients who attend leprosy clinics with post-treatment complications. Thus we had a bias towards patients with MB leprosy which is not surprising because patients with MB leprosy are at a higher risk of developing nerve damage and reactions.et al in 17 patients with neuropathic pain attending a leprosy clinic in Hyderabad found nerve tenderness in multiple nerves.We found a significant association between neuropathic pain and nerve enlargement. Nerve enlargement is one of the diagnostic criteria for leprosy and is present in significant numbers of new patients. However, the persistence of nerve enlargement after treatment suggests that there is ongoing disease in the peripheral nerves of our patients with neuropathic pain. The association with nerve tenderness is also important because this is evidence of ongoing inflammation in the patients with neuropathic pain. A previous study by Lund The relationship of neuropathic pain with painful skin patches will require further histopathological studies such as skin biopsy evaluation of intra-epidermal nerve fibre assessment. The patients in this study are probably typical of patients who attend leprosy clinics with late complications. Sixty-six percent of patients had ongoing or a history of leprosy reactions and their medication, including steroids, thalidomide and other immunosuppressants, reflects this. It is interesting that similar numbers of patients with and without pain are taking steroids. It is interesting that we did not find an association between use of thalidomide and neuropathic pain, since painful neuropathy is a well recognised adverse affect of thalidomide.The DN4 questionnaire performed well in this group and the resource poor field setting with a sensitivity of 100% and a specificity of 92% which compares well with other analyses.Leprosy patients have a large burden of post-disease complications which are not easy to detect since the patient will not always access leprosy clinics, and health workers at general health facilities may not be able to diagnose and treat them. Neuropathic pain is a chronic complication that could possibly be prevented if nerve damage is detected at an early stage and appropriate treatment with corticosteroids is started. Although steroid treatment of even early nerve damage has a variable efficacy with 50–65% of patients responding with improved nerve function after a course of steroid treatment.The association of neuropathic pain with psychological morbidity increases the importance of neuropathic pain, not only as a physical symptom, but as a possible cause of psychiatric co-morbidity. A study on HIV associated neuropathy in South East Asia found that 20% of patients had sensory neuropathy and 36% evidence of depression.No randomised controlled trials of analgesic treatment for neuropathic pain in leprosy or even well designed exploratory studies have been reported.The main weakness of the study was that the grading of the pain intensity was not done. We also did not systematically exclude potential other pathologies such as diabetes or post herpetic neuralgia. This should be done in future studies. Furthermore, the diagnosis of psychological morbidity was not based on clinical psychiatric evaluation but on GHQ-12 scores only. For the questionnaire, we used the Hindi translation, which often had to be simultaneously translated to Marathi, and which has not yet been validated, and this may therefore have altered the results.The study demonstrates a high prevalence of neuropathic pain in patients who have completed treatment for leprosy and are generally not accounted for in leprosy statistics. The main symptom was numbness (86.4%) followed by tingling (68.2%), which differs from the findings from other studies.The DN4 is a useful and simple tool for the screening of neuropathic pain, which makes it appropriate for leprosy field work. Its high specificity in the study is important in its further application outside research environment, considering the chronic implications of neuropathic pain.The relationship of neuropathic pain with psychological morbidity found in this study further increases the magnitude of the problem. It will be important to continue research in this field in order to attend the needs of these patients in terms of prevention, diagnosis and treatment.Checklist S1STROBE checklist(0.09 MB DOC)Click here for additional data file.


Objectives. To investigate and compare postoperative pain after one-visit root canal treatment (RCT) on teeth with vital pulps using three different obturation techniques.Study Design. Two hundred and four patients (105 men and 99 women) aged 12 to 77 years were randomly assigned into three treatments groups: cold lateral compaction of gutta-percha (LC), Thermafil technique (TT), and Backfill - Thermafil obturation technique (BT). Postoperative pain was recorded on a visual analogue scale (VAS) of 0 - 10 after 2 and 6 hours, and 1, 2, 3, 4, 5, 6 and 7 days. Data were statistically analyzed using multivariate logistic regression analysis.Results. In the total sample, 87% of patients experienced discomfort or pain in some moment between RCT and the seventh day. The discomfort experienced was weak, light, moderate and intense in 6%, 44%, 20% and 6% of the cases, respectively. Mean pain levels were 0.4 ± 0.4, 0.4 ± 0.3, and 1.4 ± 0.7 in LC, BT, and TT groups, respectively. Patients of TT group experienced a significantly higher mean pain level compared to other two groups (p < 0.0001). In TT group, all patients felt some level of pain at six hours after RCT.Conclusions. Postoperative pain was significantly associated with the obturation technique used during root canal treatment. Patients whose teeth were filled with Thermafil obturators (TT technique) showed significantly higher levels of discomfort than patients whose teeth were filled using any of the other two techniques. Key words:Postoperative pain, root-canal obturation, root-canal treatment, Thermafil. Pain is an unwanted yet unfortunately common sensation after root canal treatment (RCT) which commences a few hours or days after treatment and is always an unpleasant experience for both patients and clinicians -2. Root The reasons for postoperative pain can be many including chemical, mechanical, or microbial injuries to the periapical tissues that result in acute inflammation . No signMechanical factors, including over instrumentation or extrusion of root-filling materials, have been associated to the presence of postoperative pain ,5, suggeThe aim of this study was to evaluate and compare postoperative pain after one-visit RCT using three different obturation techniques.Patient selectionThe Ethics Committee of the University approved the investigation. Consecutive patients (n = 338) attending a trained endodontist (LOA-E) for primary RCT on only one tooth were invited to participate in this prospective study. All diagnoses were vital pulps, either asymptomatic irreversible pulpitis caused by carious exposures, either normal pulp of patient being referred for intentional endodontic therapy for prosthetic reasons. The individual diagnosis was confirmed by obtaining the dental history, periradicular radiographs, periodontal evaluation, percussion, and cold test . Previous NSAIDs or antibiotic treatment was recorded.All patients were informed of the aims and design of the investigation, and the first 270 that agreed to participate and signed an informed consent were included in the study. Patients were supplied written instructions on how to assess and record the postoperative pain. However, only 204 patients (105 men and 99 women), with ages ranging 12 to 77 yr  could be analysed finally because 66 subjects (dropout rate = 24%) did not completed and/or returned the questionnaires.Selection of the obturation technique Ninety patients were randomly assigned to each one of the three obturation techniques: 1) treatment with cold lateral compaction of gutta-percha (Group LC); 2) treatment with Thermafil technique (group TT); and treatment with Backfill Thermafil obturation technique (group BT). After drop out, 80 patients were assigned to LC group, 61 to TT group, and 63 to BT group.  summarizEndodontic protocolAll teeth were cleaned, shaped, and obturated during the patients’ first visit. Local anaesthesia was achieved by local infiltration with 4% articaine with 1:100,000 epinephrine  or, in hypertensive patients (8%), 3% mepivacaine without vasoconstrictor . After anesthesia, an endodontic access cavity was established by using 014 round carbide and Endo Z burs . Canals were prepared using the step-back technique with hand instrumentation. A glide path was established with stainless steel hand instruments up to a size #10. Cleaning and shaping preparation was achieved using middle-coronal preflaring carried out with Gates Glidden burs  . Patency was established and verified with #10 files. The ideal working length was determined using an electronic apex locator  and periapical radiographs. The canal was cleaned and shaped by hand with K-Flexofiles . The final instrumentation size was determined as three sizes larger than the first file binding at the working length. Master apical files ranged from #25 to #50, depending on both root anatomy and initial diameter of the root canal. Apical preparation was completed using step-back at 1-mm increments. Irrigation was always performed with 5.25% NaOCl solution.The teeth of the LC group were obturated with cold lateral compaction, using AH Plus  and gutta-percha . AH Plus was mixed according to the manufacturer’s instructions. The master gutta-percha cone was coated with AH Plus sealer, placed into the root canal, and fitted to the working length. Then, the gap for accessory cones was created using a #25 finger spreader . Excess gutta-percha was removed using a warm excavator.Thermafil technique, with a plastic carrier, was used to obturate the teeth of the TT group. A thin layer of AH Plus sealer was placed into the root canal with a paper point. A Thermafil obturator (taper .04), selected after verification, was heated in the Thermaprep® Plus Oven . The heated obturator was slowly inserted into the canal to the previously determined working length. A plugger was used to condense the coronal gutta-percha around the carrier until the gutta-percha hardened. Excess coronal gutta-percha and the plastic handle were removed with a round bur  at 2000 rpm, without water cooling. Then, the gutta-percha was vertically condensed with pluggers nº 1/2 and 3/4 .The teeth of the BT group were obturated with the modified master cone heat-softened backfilling technique , as described by Da Silva et al. . A guttaIn the three groups, the teeth were temporized using a sterile cotton pellet and Cavit .Pain / discomfort assessmentEach patient received instruction on how to use a questionnaire for the numeric and verbal evaluation of pain / discomfort . The queStatistical analysisRaw data were entered into Excel . The relationship between obturation techniques and clinical factors and postobturation pain was analyzed using odds ratio as well as logistic regression models based on bivariate and multivariate analysis (p < 0.05). Student t test was used to compare mean pain levels. The SPSS statistical software  was used.Seventeen percent of patients showed no postoperative pain, but 83% experienced discomfort or pain in some moment between the intervention and the seventh day. The discomfort experienced was weak, light, moderate and intense in 6%, 44%, 20% and 6% of the cases, respectively. describe describePostoperative pain levels when the TT obturation technique was used are described in . All theThe percentages of patients feeling pain in the total sample and in each treatment group are shown in Fig. . There wMean pain level for all techniques was 0.71 ± 0.46 Fig. . Mann-WhMultivariate logistic regression analysis was run for the dependent variable “presence of pain after 6 hours”, adjusting for age, pulpal status, NSAIDs pre medication, obturation technique and treatment length as covariates. Analysis showed that age (p = 0.03) and pre medication with NSAIDs (p = 0.0021) were factors associated statistically to the presence of pain at 6 hours, but obturation technique did not correlated significantly .The purpose of this study was to compare the postoperative pain after endodontic therapy on teeth with vital pulps using three different obturation techniques. As long as we know, this is the first study analyzing this topic. The results of this study suggest that the TT obturation technique is significantly associated to higher postoperative pain levels.Mild discomfort after root canal treatment is a common experience for patients . The reaOne of the main problems in studying pain is the patient’s subjective evaluation and its measurement. For this reason, the methodology used in assessing pain level is critical . In thisPostoperative pain is common after endodontic treatment, so it is very important for the dentist to control this pain as well as to know how widespread the problem is . Root caResults of the present study show that, although seventeen percent of patient showed no postoperative pain at any time, strikingly, 83% experienced some pain level during the week after the root canal treatment. This percentage of patient feeling pain is the highest reported in the literature -6. This Analyzing the time course of the reported pain, results show that maximum pain level occurs six hours after the treatment in the three groups, as well as the percentages of patients feeling pain . This result agrees with the findings of other studies ,23 that Results of the present study demonstrate that, at every time, mean pain level was higher in the patients treated with the TT technique. Moreover, mean pain level with TT technique was more than twice at all times, compared to LC and BT filling techniques. Strikingly, all the patients treated with the TT technique reported some pain at 6 hours (p < 0.01). Higher pain levels associated to TT obturation technique can be explained by the extrusion of gutta-percha that frequently occurs when this technique is used . Da SilvThe type of root canal instrumentation technique can influence on the discomfort or pain experienced during endodontic therapy. Goreva and Petrikas  reportedIn the present study, NSAIDs medication prior to root canal treatment was associated to higher levels of postoperative pain. Without doubt, the use of NSAIDs correlates with the presence of preoperative pain. Several studies have established that preoperative pain is a major determinant of postoperative pain or flare-up ,28,29. NNo correlation between pulpal status and post-operative pain levels has been found, in agreement with the result of Harrison et al. . HoweverThe outcome measure of future studies should be reported in terms of improvement or deterioration of pain level rather than mere prevalence of postoperative pain/flare-up .