The aim of this triple-blind full-randomized clinical trial was to quantify analgesia in masticatory muscles and temporomandibular joints after occlusal splint therapy associated with the adjuvant administration of nonsteroidal anti-inflammatory drugs (NSAID) isolated or associated with other therapeutic agents. Pain relief was also recorded. Eighteen volunteers who had been suffering from chronic pain in masticatory muscles due to temporomandibular disorders were selected after anamnesis and assessment using RDC/TMD translated to Portuguese. The 3 proposed treatments were NSAID (sodium diclofenac), panacea (sodium diclofenac + carisoprodol + acetaminophen + caffeine), and a placebo. The total treatment duration was 10 days, preceded and succeeded by patients' pain assessment. A washout interval of 11 days was established between each therapy. All participants received all treatments in different moments, in a full randomized crossover methodology. The assessment of drug therapies was performed using visual analogue scale for pain on palpation followed by 11-point numerical scale to quantify pain during treatment. Statistical analysis has shown that, after 10 days of treatment, all therapies were effective for pain relief. NSAID therapy promoted analgesia on the third day, while placebo only promoted analgesia in the eighth day. It has been concluded that sodium diclofenac used as splint adjuvant therapy, promotes significant analgesia in a shorter time. Temporomandibular disorders (TMD) result from musculoskeletal dysfunction of the orofacial region affecting masticatory muscles, temporomandibular joints (TMJ), and other associated structures. The main characteristics of these problems are facial and TMJ pain, headache, earache, dizziness, masticatory muscle hypertrophy, limited mouth opening, locked jaw, abnormal teeth wear, joint sounds, and others . BesidesDentist must be aware on the proper diagnosis and treatment of temporomandibular disorders, because they represent the second most frequent patients complaints  . The oriIn the management of temporomandibular disorders, it is primordial to relief the pain, preventing relevant alterations in neuronal circuits and secondary hyperalgesia caused by persistent afferent signs  which isStructural and neurochemical alterations on the central nervous system associated with the presence of psychosocial factors increase and perpetuate painful sensation, making chronic pain a great challenge for clinicians . In suchThus, the aim of this full randomized triple-blind crossover study was to quantify analgesia obtained by NSAID, associated or not with other therapeutic agents, in patients diagnosed with chronic muscle pain. The null hypothesis is that NSAID may reduce or eliminate pain resulted that from TMD.All the clinical and laboratorial steps were performed by only one researcher, to avoid interexaminer differences, standardizing procedures, and reducing result bias.Eighteen adult volunteers, both men and women, between 35 and 70 years of age (mean age 50 years), who were included in a maintenance-care program at the Faculty of Dentistry of Ribeirão Preto, University of São Paulo, were enrolled in this study. The inclusion criteria were masticatory muscle pain. The exclusion criteria included pregnancy, lactation, anti-inflammatory, or antibiotic therapy within the previous 3 months, current smokers, or individuals with any systemic condition that could influence pain management. The local ethics committee approved this study, and all of the experiments were undertaken with the informed written consent of each participant in accordance with ethical principles .A complete patient trial was carried out by using an anamnesis with questions regarding general health. There were also excluded participants on this study with (1) under 18 years old; (2) who worn removable dental prosthesis; (3) who were taking any other medicament; (4) whose health did not allow intake of those studied drugs; and (5) alcohol addict.The Brazilian Portuguese version of Research Diagnostic Criteria of Temporomandibular Disorders (RDC/TMD)  was usedAll participant enrolled in this investigation received a flat, full-covered, and rigid occlusal splint adjusted in centric relation contact position, with canine guides and simultaneous occlusal contacts. Patients were advised to use the occlusal splint during all the 10 days of investigation. The provoked pain was performed by finger pressure on both sides of masseter, temporalis, sternocleidomastoideus, trapezius, and TMJ lateral pole. Data from intensity of pain was assessed on the first and last day of study. Patients were instructed to mark on 10 mm visual analogue scales (VAS) the pain intensity of each examined site. In addition, during treatment period, patients were instructed to mark at an 11-point numeric scale, from 0 (absence of pain) up to 10 (the worst pain ever), once a day during nocturnal period, the value related pain intensity of that day.During treatment, patients were instructed to use the 3 treatment protocols proposed in this investigation: (a) NSAID (sodium diclofenac), (b) panacea (sodium diclofenac + carisoprodol + acetaminophen + caffeine), and (c) Placebo. A full randomized crossover methodology was adopted and, in this manner, all patients were submitted to all treatments in different moments. Therefore, the sequence of treatments did not follow a standardized sequence, avoiding bias. A washout interval of 11 days was respected between each proposed protocol.The drugs used in this study are displayed in During treatment, individuals were informed to take two daily medicament dosages, according to the manufacturer's recommendation, during 10 days, followed by an 11-day washout interval, started after the last dosage of each drug. All patients were instructed not to wear occlusal splint and not take any medicament during washout period.Statistical analysis was performed by an investigator not informed about medicaments compositions. Normality tests (Kolmogorov-Smirnov) were performed for the provoked pain data obtained by VAS. Most data did not present Gaussian distribution, and then a logarithm transformation was done. A 0.5 constant was added to all pain scores, to allow logarithm be used on zero scores . After tP < 0.05.For daily pain scores, statistical analysis was performed using nonparametric statistic methods. Friedman's test was applied to investigate pain value differences among each day of treatment. When differences were found, Wilcoxon's test was performed to compare the initial pain score to each subsequent treatment day. For both tests, significant differences were considered when P > 0.05), except for right masseter muscle, in which differences were observed between groups A and C (P < 0.05).Data from VAS analysis are displayed in Figures P < 0.05), except for right TMJ and right/left temporalis muscle (P > 0.05).When data from 11-point numeric scale was evaluated (daily pain scores), it significant differences were observed between all sites after treatment protocols (P = 0.00002). Wilcoxon's test results revealed differences between days 1 × 3 (P = 0.019), 1 × 4 (P = 0.019), 1 × 6 (P = 0.026), 1 × 8 (P = 0.006), 1 × 9 (P = 0.021), and 1 × 10 (P = 0.022).For A treatment (NSAID—sodium diclofenac), Friedman's test showed significant differences among daily pain scores (P = 0.00016). Wilcoxon's test results showed significant differences between days 1 × 3 (P = 0.018), 1 × 4 (P = 0.027), 1 × 5 (P = 0.002), 1 × 7 (P = 0.012), 1 × 9 (P = 0.004), and 1 × 10 (P = 0.011).Regarding B treatment (panacea—sodium diclofenac + carisoprodol + acetaminophen + caffeine), Friedman's test showed significant differences among daily pain scores (P = 0.012). Wilcoxon's test results showed significant differences only in days 1 × 8 (P = 0.025).About C treatment (placebo), Friedman's test indicated significant differences among daily pain scores  could minimize or inhibit the local releasing of inflammatory substances in many of the masticatory muscles  and TMJ Provoked pain analysis showed pain reduction on the right and left masseter, sternocleidomastoideus, trapezius, and left TMJ for all treatments. Thus, they were significantly effective in reducing pain sensation, but medicaments A and B were not more effective than placebo after 10-day treatment.Pain relief could be related to reduction of peripheral sensitization by decreasing of overload, fatigue, and inflammatory components release in masticatory muscles and TMJ , 23. TheHowever, occlusal splint associated with medicaments A or B reduced pain in an earlier moment (third day) when compared to control group (eighth day); it has been evident after patients' daily pain scores analysis. Thus, sodium diclofenac, whether associated or not, was shown to be more effective in reducing inflammation process from masticatory muscles and tissue microlesions of TMJ, when compared to placebo . Its actApparently, the use of occlusal splint reduced functional overload on masticatory muscles and TMJ, promoted bilateral balancing, and diminished muscle and joint activity  thus, prStandardized volunteers' selection based on their TMD signs and symptoms using RDC/TMD was possible, although psychosocial factors could have great variation among them . It meanEven in chronic pain patient who, according to biopsychosocial pain model, usually has no notable sensorial component when compared to amount of psychosocial factors, the inflammation management using medicaments showed in our investigation significant results in pain relief.Although participants in this study were chronic TMD patients, with painful complaints strongly influenced by psychological and social status, treatments were based on noxious input decreasing, by drug intake and use of occlusal splint, but analgesia was obtained in a short time and could have a positive effect on patients expectations related to treatment, making them believe in good results, changing their behavioral in regard to their problems, and improving the psychosocial pain components .Management of those drugs in a short period is important to avoid gastric, intestinal, renal, and hepatic problems, as described in the literature . All NSAAcetaminophen is usually well tolerated at therapeutic doses but may have chronic renal or hepatic adverse effects . Muscle Carisoprodol abuse is reported in the literature , and itsManagement of chronic pain is not frequently limited to pharmacotherapy and splint therapy. It should be multidisciplinary, focusing all pain aspects according to biopsychosocial model. The correct and effective intervention of patients suffering of pain could significantly increase their confidence on the proposed therapies. In such case, it seems that starting a treatment with occlusal splint associated to an adjuvant nonsteroidal anti-inflammatory for a short period could be very adequate.Within the limitations of this investigation, we conclude that (1) all proposed therapies evaluated reduced TMD pain after 10 days of treatment and (2) NSAID (sodium diclofenac) and panacea (sodium diclofenac + carisoprodol + acetaminophen + caffeine) were more effective than placebo, promoting significant pain relief on the third day, while placebo group promotes only on the eighth day.


OPRM1 A118G (rs1799971). The aim of this study was to investigate the association between OPRM1 genotype and subjective health complaints in patients with radicular pain and disc herniation.Earlier observations show that development of persistent pain may be associated with the genetic variability in the gene encoding for the μ-opioid receptor 1, the OPRM1 A118G was performed. The data of individuals with AA versus AG or GG were analysed separately by linear mixed models. The Subjective Health Complaints Inventory (0-81) including 27 common complaints experienced the previous month on a scale from not at all (0) to severe (3) was used as outcome. Pain, prior duration of leg pain, age, smoking status, and lumbar disc surgery were considered as covariates.A prospective, 1-year observational study was conducted at a hospital back clinic, including 118 Caucasian patients with lumbar radicular pain and MRI confirmed disc herniation. Single nucleotide polymorphism genotyping regarding the OPRM1 G-allele. All patients except female carriers of the G-allele reported a decrease in pain from baseline to 1 year. Female carriers of the G-allele reported significantly higher subjective health complaints score during the study time span than male carriers of the G-allele when controlling for pain and pain duration.In total 23 of 118 patients were carriers of the OPRM1 A118G polymorphism interaction in patients with radicular pain.The present data indicate that, when controlling for pain intensity and duration, subjective health complaints are associated with a sex -  Patients with non-specific low back pain or lumbar radicular pain often report additional subjective health complaints-4. In thOPRM1 A118G (rs1799971), may affect nociceptive signalling. For example, carriers of the G-allele seem to have less pronounced effects of opioids[2 stimulation, indicating decreased nociceptive activation[The single nucleotide polymorphism (SNP) in the human gene coding for the μ-opioid receptor 1, the  opioids, increas opioids and redu A118G rs99971, mativation. Moreovetivation.OPRM1 polymorphism has been associated with other physiological processes such as immune and inflammatory function[OPRM1 G-allele could be different in men and women regarding the report of subjective health complaints.Of relevance to comorbid symptoms, the function,22, strefunction,24, subsfunction, social function, social function, and rewfunction,29. Howefunction. Our hypThis study was part of a prospective, 1 year observational study on patients with suspected lumbar radicular pain and disc herniation who were referred to a back clinic at Oslo University Hospital, Ullevål (OUS), Norway, during 2007 to 2009. Patients were invited to participate by the clinic staff. Inclusion criteria were age 18-60 years, lumbar radicular leg pain with a corresponding lumbar disc herniation at the relevant side and level confirmed by magnetic resonance imaging, and positive straight leg raise test . Exclusion criteria were lumbar spinal stenosis, previous disc surgery at the same level, lumbar spine fusion at any level, generalised musculoskeletal pain, inflammatory rheumatic disease, diabetic polyneuropathy, cardiovascular disease, cancer, psychiatric disease, neurological disease, alcohol or drug abuse, completion of another surgery within 1 month, pregnancy, non-detectable genotype, non-European-Caucasian ethnicity or poor Norwegian language. Patients received a standard clinical examination and answered a comprehensive questionnaire at baseline and at 1 year. Blood samples were taken at inclusion.Treatment followed practice as usual, without any pre-allocation or randomisation. The conservative management options comprised a brief cognitive intervention, activity guidance during the acute phase, and physiotherapy. The choice of conservative and/or surgical treatment was made at the discretion of each physician/surgeon. All participants received written information and signed an informed consent form. The study was approved by the Norwegian Regional Committee for Medical Research Ethics and the Norwegian Social Science Data Services.not at all, a little, some, and severe. The SHC score is calculated by summation of item scores. The items leg pain during physical activity and low back pain are closely related to the patient’s present pain complaint and consequently excluded in all analyses, making the total possible score 81. Data on SHC prevalence in the Norwegian general population[no pain and worst possible pain, indicating pain in activity during the last week, as used previously[The number and severity of health complaints was measured by the Subjective Health Complaints Inventory (SHC). This qupulation as well pulation,4,31. Paeviously. PatientOPRM1 alleles, A or G. After initial denaturation and enzyme activation at 95°C for 10 min, the reaction mixture was subjected to 60 cycles of 95°C for 15 seconds and 60°C for 1 min. The reactions were performed on an ABI 7900HT sequence detection system. Negative controls containing water instead of DNA were included in every run. Genotypes were determined using the SDS 2.2 software (Applied Biosystems). Approximately 10% of the samples were re-genotyped, and the concordance rate was 100%.Genotyping was performed after finished patient sampling. Genomic DNA was extracted from whole blood cells using FlexiGene DNA isolation kit (Qiagen), and single nucleotide polymorphism (SNP) genotyping was performed using predesigned TaqMan SNP genotyping assays (Applied Biosystems). Approximately 10 ng of genomic DNA was amplified in 5 μl reaction mixture using a 384-well plate containing 1x TaqMan genotyping master mix (Applied Biosystems) and 1x assay mix. The latter contained the respective primers and probes. Probes were labelled with the TaqMan reporter dyes Fam™ and Vic® to distinguish between the best fit approach, assessed by the small-sample version of Akaike’s information criteria (AICc)[Genotypes were dichotomised into AA carriers  or *G carriers  because only one patient was homozygous GG. Analyses were performed separately for female *G versus male *G carriers, female AA versus female *G carriers, male AA versus male *G carriers, as well as female AA versus male AA carriers, using a linear mixed effects model approach. The outcome variable was SHC during the study time span. Both baseline and 1-year scores were included in the model. This was done to examine change over time by testing interactions between SHC and time. Pain, as measured at baseline and 1 year, duration of leg pain prior to inclusion, age, smoking status, and lumbar disc surgery during the follow-up were tested in univariate analyses. Multivariate analyses were built by including variables from the univariate analyses with p < 0.1. The baseline model consisted of the fixed factors shown in Table a (AICc). The finOPRM1 G-allele, corresponding to a G-allele frequency of 10.2% in total . One woman was homozygous GG. Patient characteristics according to sex and genotype are presented in Table In total, 118 patients were included in the study of whom 112 (95%) completed the 1-year follow-up. 23 patients were carriers of the b = 6.59, 95% CI 1.2, 11.37), whereas the effect of pain  and prior pain duration  was less pronounced. The subject-specific random factors had a significant effect in the final model . When including SHC x time interaction the overall model fit was significantly reduced and this interaction was therefore not included in the final model. The final model and estimates of covariance parameters is presented in Table The results from the final linear mixed model, including pain intensity and duration, showed that female *G carriers had significantly higher SHC score than male *G carriers, F 1, 44) = 7.73, p = 0.008. This effect of sex had a clear influence on SHC  = 1.63, p = 0.206, between male AA and *G carriers, F  = 2.48, p = 0.122 or between female and male AA carriers, F  = 0.63, p = 0.43.OPRM1 polymorphism. During the study time span female *G carriers reported significantly higher SHC scores than male *G carriers. This was true also when controlling for pain intensity and prior duration of pain. Hence, the present data demonstrate that SHC may be a trait that in itself is linked to the OPRM1 genotype. Moreover, our results show that SHC in patients with lumbar radicular pain and disc herniation are associated with a specific sex - OPRM1 polymorphism interaction. Previous data demonstrate an increase in SHC in patients with longer duration of radicular pain, indicating SHC to be secondary to pain and disability[The present study shows that multiple subjective health complaints (SHC) are associated with the sability. Our anaOPRM1 polymorphism interaction observed in the present study clearly support earlier findings. For example, it has been reported that μ-opioid receptor binding potential may be higher with increasing age and in women[OPRM1 levels between individuals with AA and G alleles have been demonstrated[OPRM1 genotype may influence stress responses, immune and pro-inflammatory responses[The sex - in women. Moreovenstrated. Additioesponses,35-37, aesponses. Also, aesponses. ExactlyOPRM1 polymorphism leads to a substitution of the amino acid asparagine (N) to aspartic acid (D) at position 40 of the extracellular receptor region. This affects the glycosylation site of the receptor, which is important for cellular processes such as receptor folding, sorting, expression and ligand binding[It is, however, now well established that the  binding. The lev binding, which m binding. Hence, The SHC Inventory captures similar symptoms as described in phenomenon such as medically unexplained symptoms or somatisation,7,9. SomDuration of pain prior to baseline was an independent predictor for SHC in the present study. The female *G carriers had on average 23 weeks longer duration than male *G carriers. It is possible that duration of pain influenced the progress in SHC and pain scores - and that with longer durations also men would report increasing subjective health complaints. It has been shown in a similar cohort with lumbar radicular pain patients that those who report their pain as unchanged or worse, also report subjective health complaints as significantly elevated[Previous studies have reported that individuals with one or more G-alleles have a reduced analgesic response to opioids. Thus, our lack of data on medication may be a potential confounder,47. MoreOPRM1 gene in a sex-specific manner. We conclude that SHC may be a trait that in itself is linked to the OPRM1 genotype.The present data indicate that SHC in patients with radicular pain and disc herniation may be influenced by a polymorphism in the OPRM1: μ-opioid receptor 1; SHC: Subjective health complaints.SNP: Single nucleotide polymorphism; The authors declare that they have no competing interests. No support was received from commercial sources.EH, EIS, CR and JG participated in the research design. EIS, CR, JG carried out the data collection. EH, LG, AJH and JG carried out the data analysis and drafting. All authors read and approved the final manuscript.The pre-publication history for this paper can be accessed here:http://www.biomedcentral.com/1471-2474/15/161/prepubEnglish version of the Subjective Health Complaints Inventory.Click here for file


Anal fissure (AF) is a common cause of anal pain with a tendency not to heal spontaneously because of ischemia of the anoderm caused by sphincter spasm. Lateral internal sphincterotomy, while very effective, can cause fecal incontinence and chemical sphincterotomy by application of cream may have discouraging side effects and/or low efficacy. The aim of this prospective multicenter study was to evaluate the safety and effectiveness of a new medical treatment based on Emulgel cream, with emollient, soothing and protective agents, on AF healing.® Emulgel (THD S.p.A Correggio (RE), Italy). Before treatment, they had a proctologic examination and pain was measured using a visual analog scale. THD Levorag® Emulgel was applied every 12 h for 40 days. Monitoring was scheduled at 10, 20 and 40 days. At time 0 and at the end of treatment, patients underwent anorectal manometry, if possible.Consecutive patients with AF treated in nine coloproctology units during 6 months entered the study on topical treatment with Levoragp < 0.001. Pain and resting anal pressure decreased significantly after treatment.Two hundred eighty-four AF patients were recruited (171 acute fissures). Complete healing was achieved in 47.9 % of the cases, an improvement in 31.0 % . In patients with acute fissure, the rate of efficacy was 89.4 % , in those with chronic fissure the rate of efficacy was 62.8 % , ® Emulgel proved to be effective for the reepithelization of AF and the reduction of pain in the short term in about 80 % of patients.Treatment with THD Levorag Anal fissure (AF) is one of the most common anorectal disorders, and, in Italy, the second most common problem, after hemorrhoids, that brings patients to the proctologist’s office ; AF is rAF is characterized by “a linear ulcer of the anoderm, distal to the dentate line” , is usuaDespite significant progress made both in understanding the etiology and pathogenesis of AF, and in developing treatments based on internal sphincter relaxant agents , there iThe topical myorelaxant creams on the market were shown to have limited advantages when compared with placebo in randomized controlled trial , 7 and spruritus ani [Furthermore, most of the myorelaxant creams available (containing nitric oxide donors) have some unpleasant side effects like headache, migraine and itus ani , 11, whiitus ani , even ifThe availability of new effective and well-accepted topical treatment, without side effects, is therefore eagerly awaited.® Emulgel , Italy), in reducing pain and in the reepithelization of AF.The aim of our prospective multicenter observational study was to evaluate the safety and efficacy of a new topical cream, LevoragAll consecutive patients with acute or chronic anal fissure examined and treated in nine coloproctology units in Southern Italy between June 2013 and January 2014, who gave their informed consent to the study, entered this prospective observational trial which qualified for “exempt” on institutional review board because it was part of the routine internal audit of the colorectal units involved in the study.Inclusion criteria were primary AF, acute or chronic disease, and age range between 18 and 65 years. Acute fissure was defined as a recent (within 1 month) ulceration of the anoderm without the typical signs of a chronic fissure  [® Emulgel for 40 days. THD Levorag® Emulgel is a gel cream in 3.5-ml single-dose tubes containing a mixture of substances with lubricating, film-forming, emollient, soothing and protective properties  will deliver the gel to the rectum instead of the anal canal. The patients were also invited to take oral laxatives in order to reduce the hardness of the stools and facilitate evacuation, and to clean their anus with disinfecting chlorhexidine-based solutions . The use of oral painkillers was allowed and recorded.Clinical evaluation of patients was scheduled at time 0, before starting the treatment, and at days 10, 20 and 40. Baseline evaluation included a proctologic exam to determine the diagnosis and the type of fissure, and recording the amount of anal pain, using a visual analog scale (VAS), and other concomitant anal symptoms. Anal manometry to document the anal resting pressure before and after treatment was carried out in two of the units involved in the study.On day ten of treatment, the patients were interviewed by phone to evaluate the level of pain and those without any improvement or with further deterioration of symptoms were dropped from the study.On day 20 of treatment, the patients underwent a proctologic examination and pain was assessed with a VAS. The degree of reepithelization of the fissure was scored as follows: 0: deep fissure still present; 1: superficial fissure; 2: partial reepithelization or 3: complete healing and reepithelization. Those without any improvement in reepithelization or pain score were dropped from the study.On day 40, the remaining patients underwent their last evaluation including a proctologic examination, anal pain score, and, if possible, anal manometry.The results were divided according to outcome (successful treatment and failure). Successful treatment was defined as complete fissure healing or partial fissure reepithelization associated with at least 50 % reduction of the pain score after completing the scheduled 40 days of treatment.http://www.raosoft.com/samplesize.html.Sample size calculation were carried out by the website Assuming the VAS score would be reduced to 50 % of the initial value, with an alpha error of 5 % and a beta error of 10 %, and considering a possible dropout rate of 5 %, a total of 281 patients were required to get statistical significance with a 90 % confidence interval and a power of the study of 90 %.p value <0.05 was considered statistically significant.All data were prospectively entered into an excel database by each of the participating centers and analyzed by the coordinating center. Qualitative data were expressed using the Wilcoxon rank sum test for paired data, while median anal manometry data and pain scores were analyzed with the Chi-square test. The ANOVA for repeated measures was performed to evaluate the changes of pain scores over time. A p = 0.8).Overall, 284 patients  were recruited in the nine colorectal units. One hundred twenty-one of them had chronic AF, and 171 had acute AF. The site of the fissure was posterior in 212 cases (74.7 %), anterior in 58 (20.4 %) and anterior and posterior in 14 (4.9 %). The median anal pain score at baseline was 8 on a 0–10 VAS (10 = worst possible pain), while anal manometry revealed high resting pressure (median 95 mmHg) in all the 50 patients examined. A similar baseline average pain score was observed in patients with acute or chronic AF , six patients interviewed by phone (1 with acute fissure) were excluded from the study because of no pain relief. One more patient (with acute fissure) was lost to follow-up.At day 20 (T2) after clinical examination, another patient (with acute fissure) was lost to follow-up and 11 patients (four with acute fissure) were excluded from the study  . In patients with acute fissure, the rate of efficacy was 89.4 % , while in those with chronic fissure, it was 62.8 %  (p < 0.005), corresponding to a 40 % reduction , but without a significant difference between the acute and chronic AF  or the site of the fissure, (p = 0.77) while, as expected, acute fissure were more likely to heal than chronic fissures   finally achieved complete healing. Lateral internal sphincterotomy was performed on 72 % of the patients who failed with conservative treatment (data available only from three of the nine centers).Eighty-eight patients, who improved but did not have complete fissure healing at the end of the study period, spontaneously prolonged the treatment with THD LevoragAfter the pathogenic mechanisms underlying the tendency of AF not to heal spontaneously were clearly described by Schouten and co-workers  and by LThe need of further medical solutions to this painful disease has therefore been eagerly awaited.® Levorag® Emulgel can help about 89 % of patients with acute AF and 63 % of those with chronic AF, leading to complete fissure healing in 64.3 and 23 % of acute and chronic AF, respectively, and allowing a significant reduction of anal pain after the first week of treatment and in the following weeks. Moreover, a further percentage (about 15 %) of fissures not yet healed within the study period completed the healing process in the next 20 days of treatment. The adoption of strict criteria for defining fissure healing, used for the first time in this study, made the results of treatment even more reliable. Another limitation of this study is that it was explicitly designed to evaluate the ability to control the anal pain which is the major patient complaint, and therefore, the sample size was calculated based on this instead of the healing rate.Although the lack of a control group is an important limitation to our study, this large multicenter prospective trial shows that topical treatment with THD® Emulgel resulted in a good patient compliance and no side effects, while the reduction of the anal resting tone was documented in a significant subgroup of these patients.The association of substances promoting tissue healing contained in THD Levorag® Emulgel was proven to be an effective and well-tolerated topical treatment for both acute and chronic AF in the short term, constituting one more arrow to the bow of proctologists in treating this painful disease, and compares well with the other conservative medical treatments even if the long-term outcome remains to be evaluated.THD Levorag


People around the world suffer chronic lower back pain. Because spine imaging often does not explain the degree of perceived pain reported by patients, the role of the processing of nociceptor signals in the brain as the basis of pain perception is gaining increased attention. Modern neuroimaging techniques  have produced results that suggest which brain areas may play a crucial role in the perception of acute and chronic pain. In this study, we examined 12 patients with chronic low back pain and sciatica, both resulting from lumbar disc herniation. Structural magnetic resonance imaging (MRI) of the brain was performed 1 day prior to and about 4 weeks after microsurgical lumbar discectomy. The subsequent MRI revealed an increase in gray matter volume in the basal ganglia but a decrease in volume in the hippocampus, which suggests the complexity of the network that involves movement, pain processing, and aspects of memory. Interestingly, volume changes in the hippocampus were significantly correlated to preoperative pain intensity but not to the duration of chronic pain. Mapping structural changes of the brain that result from lumbar disc herniation has the potential to enhance our understanding of the neuropathology of chronic low back pain and sciatica and therefore may help to optimize the decisions we make about conservative and surgical treatments in the future. The possibility of illuminating more of the details of central pain processing in lumbar disc herniation, as well as the accompanying personal and economic impact of pain relief worldwide, calls for future large-scale clinical studies. The first group consisted of 12 LDH patients  with LBP and sciatica. Each patient had been experiencing chronic pain for at least 3 months (mean pain duration: 9.3 ± 5.4 month). All patients were diagnosed, using spinal MRI, with an isolated LDH at either level L4-5 or L5-S1. Half of these patients suffered from sciatica located in the left lower limb and half from right-sided sciatica. The spinal MRI was assessed using the usual clinical routine by experienced neurosurgeons and neuroradiologists. The second, or control, group consisted of 12 subjects age and gender matched to the first group. The members of this control group had no history of any chronic pain or neurological disorders. All participants gave their informed written consent. Prior to the MR imaging, patients and control-group volunteers were examined neurologically. The initial mean level of back pain was quantified using a common visual analog scale (VAS) ranging from 0 to 10 points, where 0 points indicates no pain. The control group reported a mean pain intensity of 0 and the neurological examination revealed no neurological deficits. Any changes in patients' VAS scores were assessed using a paired A high-resolution MRI image of each patient's brain was acquired 1 day prior to his or her scheduled microsurgical lumbar discectomy. All patients underwent a complication-free surgery on the following day, at either level L4-5 or L5-S1. A second MRI was taken 4 weeks after the patient's discharge from the hospital (mean time between both imaging sessions 36.8 ± 3.1 days). The subjects from the control group were also scanned twice, with a temporal gap of 38.0 ± 3.9 days between the two MRI sessions. No member of the control group underwent any intervening medical procedures.3.MR imaging was conducted on a 3 Tesla Siemens Magnetom Trio scanner  using an 8-channel phased-array head coil. A high-resolution anatomical dataset of the entire brain was acquired using a T1-weighted, magnetization-prepared rapid gradient-echo (MPRAGE) sequence  resulting in an isotropic voxel resolution of 1 mmp = 0.05) for multiple comparisons in the context of Gaussian random field theory  implemented in VBM8 was applied . The subsequent analyses were conducted with SPSS .Additionally, to assess the relevance of preoperative pain intensity and duration and the impact of postoperative changes of the pain to the structural alterations found in the VBM analysis, we performed regression analyses  using preoperative VAS scores, pain duration and the postoperative pain alteration as independent variables in an additional step in order to predict the changes in GM volume (dependent variable). For this purpose the corresponding voxels were extracted using the toolbox Marsbar  than the preoperative score, with a mean value of 1.8 ± 1.1, ranging between 0 and 4.LDH patients reported a preoperative mean pain intensity level of 7.2 ± 0.9, ranging between 6 and 9. All of these patients suffered from LBP and unilateral sciatica that radiated into at least one leg in a classic dermatomal distribution (The mean preoperative pain duration was 37 ± 21.7 weeks). For each of them, the pain had been accompanied by numbness and tingling for at least 3 months. The clinical examination revealed no motor deficit in any patient. The MRI examination of the spine discovered LDH at the level of L4-5 in five patients and at the level of L5-S1 in seven patients. All operations were performed without any ensuing complications. The postoperative VAS score at the time of the second MRI examination was significantly lower , we observed a significant alteration in the GM volume of patients who had undergone surgical treatment to relieve chronic low back pain (cLBP) and sciatica resulting from lumbar disc herniation (LDH). After correcting for multiple comparisons, we found in these patients a region within the hippocampus where the GM had decreased in volume after surgery. We observed an increase in GM volume, however, in the putamen and pallidum, parts of the basal ganglia Figures . The regIn recent years, a large body of evidence has revealed structural brain alterations associated with several chronic pain syndromes May,  similar The hippocampus and the BG are part of the contemporary model of the pain matrix and, as such, are believed to be crucially involved in pain processing and modulation. Recent evidence suggests that the BG are uniquely involved in the thalamo-cortico-BG loops that integrate the motor, emotional, autonomic, and cognitive aspects of chronic pain . Also, the VBM analysis cannot account for the underlying cytoarchitectonic causes of the structural alterations of the CNS. Variable cell sizes, increased or decreased synaptogenesis, or a changed quantity of glial cells might account for the structural alterations found (Schmidt-Wilcke et al., Some limitations of this study should be addressed. The sample size was relatively small, but the results are significant after correction for multiple comparisons (We conclude that chronic pain due to LDH can induce structural alterations of the brain that are potentially reversible after successful discectomy. Since pain is ultimately interpreted by the brain, studying the cortical and subcortical changes of the brain that result from LDH has the potential to enhance our understanding of the neuropathology of chronic LBP and sciatica and therefore may help to optimize future conservative and surgical treatment options. Specifically, the classification of specific morphometric changes of the brain associated with the treatment of LDH may possibly prove useful in identifying individual predictive factors in the evaluation of whether a patient is likely to improve by non-surgical management or would instead benefit from surgery. It is interesting to speculate whether more advanced neuroimaging techniques and data-processing methods would enable the identification of specific patterns of altered brain functions and anatomy and thus yield additional objective diagnostic criteria that might then guide therapeutic interventions targeting the brain for effective individual management of LDH. The ability to illuminate and understand more of the details underlying central pain processing in LDH, and the potential economic impact of such an amplified understanding, to our mind justifies future large-scale clinical studies conducted to confirm or modify the results that we have presented here.The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.


Cancer patients who undergo surgery or radiation can develop persistent focal pain at the site of radiation or surgery. Twelve patients who had surgery or radiation for local cancer and failed at least two analgesic medications for pain control were prospectively enrolled in a research protocol. Patients were injected up to 100 units of incobotulinum toxin A (IncoA) intramuscularly or subcutaneously depending on the type and location of pain (muscle cramp or neuropathic pain). Two patients passed away, one dropped out due to a skin reaction and another patient could not return for the follow up due to his poor general condition. All remaining 8 subjects  demonstrated significant improvement of Visual Analog Scale (VAS)  and reported significant satisfaction in Patients’ Global Impression of Change scale (PGIC) (7 out of 8 reported the pain as much improved). Three of the 8 patients reported significant improvement of quality of life. Surgery and radiation for cancer treatment has focal side effects on skin, soft tissues, muscles and nerves leading to muscle atrophy, fibrosis and contracture ,2,3. AppBotulinum neurotoxins (BoNTs) block the release of neurotransmitters from presynaptic vesicles via inhibition of SNARE proteins, i.e. Soluble NSF  Attachment protein Receptor, which promote rupture of these vesicles . The undPain relief after local injection of onabotulinum toxin A (OnaA) and abobotulinum toxin A (AboA) has been reported before in a small number of patients with post-radiation/post-surgical pain  but not Adult subjects with cancer and focal chronic pain after surgery and/or radiation who have failed to respond to at least two analgesic medications were eligible to participate in the study. Participants were excluded if they had received prior botulinum toxin treatment, had diseases of neuromuscular junction or were on antibiotics or pharmaceutical agents with potential to affect neuromuscular transmission.The study was approved by the Yale Human Use Committee and registered at ClinicalTrials.gov (NCT01931865). Subjects were enrolled in the study after meeting the eligibility criteria and signing an informed consent. Demographic data, history, type of cancer, location of pain and type of medications were recorded along a neurological examination during the first visit . The levThe primary outcome in this study was improvement in pain as defined by 2 or more grade change in the VAS at 6 weeks after injection. The secondary outcomes were changes in the PGIC and QOL. The side effects were obtained and documented during each assessment.A total of 25 patients were screened and 12 were enrolled in the study. Four patients did not finish the study. Two died because of advanced cancer, one could not return for follow up due to poor general health and one also did not return due to a skin reaction which developed shortly after incobotulinum toxin A injection. Of the remaining 8 who completed the study, four were female. The mean age was 55 years . Patient’s demographic information is presented in All patients demonstrated significant improvement in VAS (more than two grade improvement) at 6 weeks . Five ofP, glutamate), which cause vasodilation and local inflammation. The inflammation leads to a series of complex reactions such as proliferation of CNS macrophages and impaired receptors inhibitory function. The nerve damage also increases sodium release and causes ectopic nerve discharge as a result of neuroma formation at the site of injury. These phenomena lead to sensitization of peripheral nerve endings and central sensitizations [Local post-surgical chronic pain occurs in 20%–70% of cancer patients . The cauizations ,17,18.Radiation therapy has acute and delayed side effects the magnitude of which is dose dependent. Animal studies have shown focal loss of capillaries and muscle degeneration 2–4 months after a one-time 2000 rad (20 Gy) treatment. The damage increases collagen and decreases proteoglycans in extracellular matrix leading to disorganized structure and fibrotic tissue formation . Focal pData from animal studies have proposed a variety of mechanisms to explain the botulinum toxin (BoNT) induced analgesia after local injection. The data suggests that both peripheral and central mechanisms play a role in BoNT induced analgesia, although the exact mechanisms still not clear. Animal data demonstrates inhibition of substance P and calcitonin gene related peptide (CGRP) release from dorsal root ganglia (DRG) after peripheral injection ,21 and mi.e., improvement of pain by two or more grades as assessed by VAS. Seven of the eight patients also reported significant satisfaction with treatment (secondary outcome-PGIC). The rather low number of patients (3 out of 8) who showed improvement of QOL in this study is in contrast with VAS and PGIC results. This is most likely due to the complexity of the quality of life questionnaire and to the fact that in patients with advanced cancer, many factors other than pain influence the quality of life. Considering the high incidence of placebo response in subjects with pain, the value of VAS in this population need to be evaluated in a blinded study. Incobotulinum toxin A treatment improved both muscle spasms and neuropathic pain (burning and jabbing pain). This finding is in agreement with the prior reports on the efficacy of other botulinum toxin as in management of this type of human pain (This is the first report on the efficacy and safety of incobotulinum toxin A in cancer patients with post-surgical and post-radiation pain. In this prospective study, all patients met the primary outcome man pain . Prior sIn conclusion, the result of our study and other open studies suggests the efficacy and safety of all three types of BoNT-A in alleviating the chronic pain in cancer patients after surgery or radiation. The limitation of these studies is the small number of the studied subjects and the open design of these studies. Blinded, placebo-controlled studies are necessary to support or refute the efficacy of botulinum toxin injections in relieving post-surgical or post-radiation pain in cancer patients.


Patients with back pain radiating to the leg(s) report worse symptoms and poorer recovery than those with back pain alone. Robust evidence regarding their epidemiological profile is lacking from primary care, the setting where most of these patients will present and be managed. Our objective was to describe the characteristics of patients with back and leg pain, including sciatica, seeking treatment in primary care.Adults visiting their general practitioner with back and leg pain, of any duration and severity, were invited to participate. Participants completed questionnaires, underwent clinical assessments and received MRI scans. Characteristics of the sample are described, and differences between patients diagnosed with referred leg pain and those with sciatica are analysed.Six hundred nine patients participated; 62.6 % were female, mean (SD) age 50.2 (13.9). 67.5 % reported pain below the knee, 60.7 % were in paid employment with 39.7 % reporting time off work. Mean disability (RMDQ) was 12.7 (5.7) and mean pain intensity was 5.6 (2.2) and 5.2 (2.4) for back and leg respectively. Mean sciatica bothersomeness index (SBI) was 14.9 (5.1). Three quarters (74.2 %) were clinically diagnosed as having sciatica. In the sciatica group, leg pain intensity, neuropathic pain, pain below the knee, leg pain worse than back pain, SBI and positive MRI findings were significantly higher as compared to patients with referred leg pain.This primary care cohort reported high levels of disability and pain. This is the first epidemiological study of unselected primary care patients seeking healthcare for back and leg pain. Follow-up of this cohort will investigate the prognostic value of their baseline characteristics. This new information will contribute to our understanding of the characteristics and clinical features of this population, and will underpin future research aimed at defining prognostic subgroups to enable better targeting of health care provision. In primary care, approximately 60 % of patients presenting with low back pain (LBP) also report pain in the leg(s) . Leg paiOne reason for this confusion and lack of clarity in the guidelines relates to the poor evidence base regarding outcome and treatment effectiveness for LBP patients with related leg pain.Few studies exist which describe the characteristics and clinical course of the full range of patients seeking care for low back and leg pain/sciatica. Most studies focus on patients with back pain alone, include mixed populations with back and leg pain (without differentiating between them), or are concerned with describing the characteristics of highly selected populations from tertiary care settings . Robust evidence regarding the epidemiology of low back related leg pain (including sciatica) is lacking from primary care, the setting where the majority of these patients will present and be managed.Information about the broad group of patients with LBP and leg pain presenting to primary care will contribute to our understanding of the characteristics and clinical features of this population, and will help patients, health care practitioners and managers better define and deliver appropriate health care provision.The main objective of this study is to describe the characteristics, imaging findings and clinician defined specific diagnosis, in patients with low back and leg pain seeking treatment in a primary care setting.We also investigated key differences in patients’ characteristics between the groups with and without a clinical diagnosis of sciatica as clinicians consider them to have different natural and clinical courses, and potential management options for each group also differ. For consistency we use the terms “sciatica” and “referred leg pain” throughout this paper to denote those with, and without, clinically diagnosed presence or absence of spinal nerve root involvement.Assessment and Treatment of Leg pain Associated with the Spine) has been published [This paper presents baseline data from a prospective observational cohort of primary care consulters with back and leg pain/sciatica (ATLAS). The protocol for the ATLAS study  with LBP and associated leg pain of any duration and intensity but without spinal ‘red flags’ or serious physical or mental comorbidities thought likely to preclude their ability to attend a research clinic  performing the assessments were senior staff with experience in the assessment and treatment of spinal musculoskeletal conditionsAll patients attending the research clinic and after giving written consent, received a standardised assessment by a study physiotherapist to confirm eligibility and agree a treatment plan. All study physiotherapists . Care pInformation was collected on age, gender, employment status, type of work, interference of pain with work performance , 12 (meaDisability was measured with the Roland Morris Disability Questionnaire (RMDQ) leg pain version which has 23 items scored from 0 to 23 with higher scores indicating higher disability , 14. BacAnxiety and depression were measured using the Hospital Anxiety and Depression scale (HADs) with scores from 0 to 21, higher scores indicate higher levels of anxiety/depressive symptoms, with a cut-off point of ≥11 considered to indicate ‘probable depression/anxiety’ . Pain seParticipants underwent a standardised clinical assessment including subjective history and physical examination and an MRI scan. The assessors were asked to indicate whether the presence of leg pain was due to sciatica or to referred leg pain and their confidence (percentage) in their clinical impression/diagnosis and to indicate a specific diagnosis for the sciatic symptoms  (for full details on assessors training see study protocol ).MRIs were scored by a single assessor: a senior consultant musculoskeletal radiologist (JS) blind to any specific clinical information relating to patient’s symptoms other than the patient presentation with back and leg pain (not stating which leg). The assessor provided a clinical report indicating the presence/absence of definite or possible nerve root compression by lumbar spinal level (3 lower lumbar levels) and side (right/left) and the reason(s) for it if present  as per normal practice in radiological reporting.Descriptive data for the whole sample are presented as means and standard deviations for continuous variables and as frequency counts and percentages for categorical variables.Key characteristics were compared between patients with and without a clinical diagnosis of sciatica using two-sample t-tests for continuous variables  and Pearson’s Chi-squared test for categorical variables (Fisher’s exact test used for cell frequencies <5). The key variables included: age, gender, smoking, BMI, back and leg pain scores, disability, anxiety and depression, work interference and any time off work, first ever episode, worse pain in low back or leg, pain below knee, neuropathic pain score, sciatica bothersomeness index score and sleep disturbance, STarT Back tool score, MRI findings.Two thousand and eighty seven potentially eligible patients identified at primary care visit were invited to the study; 1310 attended the research clinic, and 614 consented and were eligible to participate. The detailed flow of patients into the study is presented in Fig. Of the 614 patients in the study, five patients were (subsequently) excluded from the study and referred on to secondary care services following their MRI results, as they were found to have initially unsuspected serious/specific pathologies. These were: avascular necrosis of the femoral head (AVN), thoracic spinal cord compression, widespread metastatic cancer, large benign pelvic cyst/tumour. All four cases presented at baseline assessment as sciatic pain, and one case of inflammatory arthritis presented as referred leg pain. Based on the above numbers the rate of unsuspected specific/serious pathologies causing back and leg pain in this sample of primary care consulters was 0.8 % (5/614). A further three patients were incidentally found to have stage IV renal carcinomas (pain free) and were referred to the appropriate secondary care services but remained in the study as these were not spinal pain related findings. The final sample in the study was 609 patients. Overall, 9.1 % of the participants (55/614) did not have the MRI scan, most of them declined due to claustrophobia, plus four having contraindications to the procedure.The sociodemographic, physical and psychological profiles, including imaging findings, of all study participants are presented in Tables The mean age of participants was 50.2 (13.9) years with a range of 18 to 82 years; 15.1 % of participants were 65 years of age or over. 62.6 % were female. Mean BMI was 29.9 (7.0). 60.7 % (367) were in paid employment and 47.7 % of the cohort were in routine and manual occupations. Over a third of the cohort (39.3 %), were not currently in a paid job. Of those in employment, 39.7 % reported having time off work due to their current episode of back and leg pain, either self-certified or with formal sickness certification. Almost a third (31.9 %), were current smokers.Only 9.5 % of patients reported that this was their first episode of back and/or leg pain and nearly half, had symptoms for over 3 months. Mean (SD) disability score, as measured by the RMDQ, was 12.7 (5.7). Mean leg pain intensity was 5.2 (2.4) and 67.5 % reported pain below the knee. Mean SBI composite score was 14.2 (5.4). Almost half (48.1 %) scored ≥12 points on the S-LANSS, indicating possible neuropathic pain. Most patients (70.3 %) reported sleep disturbances due to their back and/or leg pain. Mean scores for anxiety and depression as measured by the HADs were 7.8 (4.2) and 6.4 (4.0) respectively. 86.1 %  were at risk of future persistent disability as measured by the STarT Back screening tool.Based on the clinical assessment, 74.2 % (452/609) of the sample was diagnosed as having sciatica. Diagnosis was reached with variable degrees of confidence (range 50 to 100 %). In 70 % of all cases the confidence in clinical diagnosis was ≥80 % with a similar distribution of confidence range for patients with and without sciatica. Specific clinical diagnoses for the sciatica group were: disc prolapse; 53.7 %, stenosis ; 10.6 % and in 35.7 % no specific pathoanatomical diagnosis was made for the presenting sciatic symptoms.Of the 554 patients having an MRI scan, 37.8 % were found to have evidence of definite nerve root compression and 15.9 % of possible nerve root compression, on the relevant side. Among those with a clinical diagnosis of sciatica, 60.7 % had definite or possible nerve root compression on MRI compared to 32.4 % of those diagnosed with referred leg pain.n = 252), 79.8 % had a disc prolapse accounting for nerve root compression, including three cases of cauda equina compression. Stenosis was reported in 18.2 %, with another three cases of nerve root compression due to osteophytes, one due to a synovial cyst and one due to epidural lipomatosis constricting the theca.In the sciatica group with positive MRI findings (n = 45), 68.9 % had a disc prolapse and 24.4 % had stenosis.In the referred leg pain group with positive MRI findings .Although it is not possible to provide detailed data on the characteristics of non-responders to the clinic invitation, those who were non-eligible or declined participation, comparison of age, gender and area deprivation for participants and non-participants shows reasonable comparability in these three key baseline characteristics. Slightly more women (63 % vs 57 %), slightly younger patients (mean age 50 vs 55) and slightly more patients from least deprived area tertile (36 % vs. 31 %) participated, which is a common finding in the literature. There were no significant differences in characteristics between patients undergoing an MRI and those that did not (data not presented).In this paper we describe the characteristics of 609 primary care patients seeking care for symptoms of back and leg pain including sciatica. To our knowledge this is the first, primary care cohort of patients seeking care for back and leg pain, including symptoms of any duration and severity, to be described in detail.In this group of patients with back and leg pain mean levels of pain and disability were moderate, nearly half had symptoms for over 3 months, over two thirds reported pain related sleep disturbances, and the majority scored at medium or high risk of future back pain related disability. Nearly three quarters of the participants were clinically diagnosed as having sciatica, with diagnostic confidence of 80 % and over for the majority. Approximately half of this cohort was likely to have pain of neuropathic nature as measured with self-reported validated scales. MRI findings of nerve root compression were present in just over half of the participants. Unsuspected serious pathologies , detected because of the MRI scans, were 1.3 %.Only 9.5 % of patients in this cohort were experiencing a first ever episode of back and leg pain, although the majority were in the sciatica group. This is in line with evidence that back problems with or without leg pain are recurrent, with the majority of consulters reporting previous symptoms , 24. ThiMean BMI in this cohort was 30, which is higher compared to the general population . AnalysiWe used a self-reported neuropathic questionnaire to assess the presence of possible neuropathic pain. A higher proportion of patients in the sciatica group had scores indicative of neuropathic pain compared to the referred leg pain group. Sciatica is considered a type of peripheral neuropathic pain syndrome –30. HoweDisability mean level, as measured by the RMDQ, was higher 12.7) compared to other primary care consulting research cohorts with back pain with or without leg pain ((8.8) 2.7 compa, (9.0) ), but loOverall, this study shows that primary care patients with back and leg pain have pain and impact approaching those seen in secondary care, and much worse than primary care back pain samples but with similar psychological status.We used the STarT Back screening tool  to measuApproximately two thirds of the sciatica group and one third of the referred leg pain group had evidence of nerve root compression on MRI, with a disc prolapse being the most common finding in both cases. This is in line with well documented evidence that clinically diagnosed sciatic symptoms are not always supported by MRI findings and MRI evidence of nerve root compression may be present in the absence of any symptoms . There iAs this study aimed to identify everyone seeking care for symptoms of back and leg pain the findings can be used to estimate the general population prevalence of clinically assessed sciatica. Around 6 % of the UK general population visit their GP with back pain each year , and 61 The present study is the first to describe primary care patients seeking care for symptoms of low back and leg pain including sciatica without imposing selection criteria such as duration and severity, or strict diagnostic criteria/characteristics for defining the sciatica cases. Patients were recruited directly from general practice with computerised systems which maximises patient identification. This recruitment method, combined with the comparability of sciatica prevalence estimates (above), means that this cohort is likely to be representative of primary care patients seeking care for low back and leg pain.Although attempts were made to maximise recruitment by using computerised identification, there was still the potential for patients to be missed, for example if the GP decided to override the system. This could lead to selection bias if invited patients differed from those who were not invited, although we do not have the data to investigate this.Similarly, a number of invited patients did not attend or were not interested in participation. Age and gender characteristics for these non-participants are overall similar to those of the study’s participants. However, we do not have data on any of the other variables and therefore participation bias is a possibility if those who participated differed from non-participants on important characteristics (on which we have no data from non-participants).Another potential limitation in describing the two groups (sciatica/referred leg pain) in this cohort is potential clinical diagnostic error. Diagnostic error and uncertainty is always a factor for a condition that can present with a wide spectrum of mild to severe symptoms. Diagnosis of sciatica is a probability of having the condition, based on clinical assessment findings. We captured diagnostic uncertainty by recording level of diagnostic confidence and over two thirds of the study patients were diagnosed with confidence of 80 % and above, which we consider as an acceptable level.In summary, in this unselected primary care cohort of patients seeking care for back and leg pain, disability levels are higher as compared with cohorts including mixed populations of LBP patients with and without pain in the leg(s) and similar for both sciatica and referred leg pain presentations. Nearly three quarters of the participants were clinically diagnosed as having sciatica. Approximately half of this cohort was likely to have pain of neuropathic nature as measured with self-reported scales. In contrast to non-specific LBP, minimal treatment was applicable to only a very small number of patients in this cohort. MRI findings of nerve root compression were present in just over half of the participants. There were differences between the sciatica and referred leg pain groups in terms of leg pain levels, neuropathic pain, bothersomeness due to the sciatic symptoms and MRI findings. Follow-up of this cohort will investigate the prognostic value of their baseline characteristics and explore the clinical relevance of the differences between those with sciatica and referred leg pain for the course of the low back and leg pain episode.