The Pain Self-Perception Scale (PSPS) is a 24-item questionnaire used to assess mental defeat in chronic pain patients. The aim of this study was to develop a Spanish language version of the PSPS (PSPS-Spanish), to assess the instrument's psychometric properties in a sample of patients with fibromyalgia and to confirm a possible overlapping between mental defeat and pain catastrophizing.The PSPS was translated into Spanish by three bilingual content and linguistic experts, and then back-translated into English to assess for equivalence. The final Spanish version was administered, along with the Hospital Anxiety Depression Scale (HADS), Pain Visual Analogue Scale (PVAS), Pain Catastrophizing Scale (PCS) and Fibromyalgia Impact Questionnaire (FIQ), to 250 Spanish patients with fibromyalgia.r correlation coefficients ranged between 0.68 and 0.86). Principal components analysis revealed a one-factor structure which explained 61.4% of the variance. The test-retest correlation assessed with the intraclass correlation coefficient, over a 1-2 weeks interval, was 0.78. The total PSPS score was significantly correlated with all the questionnaires assessed .PSPS-Spanish was found to have high internal consistency , PSPS-Spanish correlates more intensely with FIQ than in patients without PTSD. Mental defeat seems to be a psychological construct different to pain catastrophizing. Mental defeat (MD) has been defined as the perceived loss of autonomy in the face of uncontrollable traumatic events, resulting in the person giving up efforts to retain identity and self-will ,2. It haAs both PTSD and depression are frequently comorbid with chronic pain, Tang et al  studied per se, but rather on the effects of pain as an assault on the person's life and sense of identity. In addition, Tang et al [One of the problems in the development of the construct "mental defeat" was its possible overlapping with another psychological construct that is considered relevant in chronic pain, pain catastrophizing (PC). PC is considered a continuous psychological variable, normally distributed even in healthy individuals without pain or depression . It has ng et al  have demDespite mental defeat appearing to be a relevant construct in chronic pain , it has The aim of this paper is to validate the Spanish version of Pain Self Perception Scale (PSPS-Spanish) in patients with FM. Another secondary objective is to confirm whether mental defeat is a concept that differs from pain catastrophizing in patients with FM.Permission to translate and validate the PSPS was obtained from the original authors . Two SpaSample size was calculated according to the recommended 10:1 ratio of number of subjects to number of test items . The samThis is the questionnaire to be validated. It has 24 items, with 11 items adapted from the PTSD mental defeat scale ,4 and 13The FIQ is a 10-item self-report questionnaire that measures the health status of patients with FM . The firThe HADS  is a selThe PVAS was designed to allow a subjective assessment of pain. A Visual Analogue Scale is usually a 10-cm horizontal line, with perpendicular lines on the edges, defined as the extreme limits of pain experience. The anchor points at each end are labeled as "No pain" (accompanied by the number "0") at one end and "maximum pain ever experienced" (accompanied by the number "100") at the other end. Previous studies have demonstrated PVAS to have adequate psychometric properties .The PCS is a 13-item self-report questionnaire that comprises three dimensions: (a) rumination, (b) magnification and (c) helplessness. Its validity and reliability have been previously reported . Our groThis is a psychiatric interview developed by our group for the multiaxial assessment of psychiatric morbidity in medical patients. It permits the use of different diagnostic criteria, including DSM-IV and International Classification of Diseases, Tenth Revision (ICD-10). It was used to diagnose psychiatric comorbidity in the sample.r correlation coefficient. To confirm that pain catastrophizing and mental defeat are different constructs, a partial correlation analysis between PSPS-Spanish and the other scales controlling pain catastrophizing was performed. Test-retest reliability, evaluated with the intraclass correlation coefficient, was assessed for the 1 to 2-week follow-up interval, during which time the patients did not change baseline treatment. All statistical analyses were performed with SPSS software, Release 15  except for the principal component analysis, which was performed with LISREL software, version 8.30 .In order to determine the suitability of the data for principal components analysis, the Kaiser-Meyer-Olkin Measure of Sampling Adequacy (KMO)  and BartDifferences between the original English-language version and the back-translated version of the PSPS-Spanish can be seen as Additional file Sixteen patients were ruled out from the study because CFS symptoms predominate. Of 253 potential subjects, three (1.1%) declined to participate. None of the participants were ruled out because of the exclusion criteria. The final study sample consisted of 250 patients, 229 (91.6%) women and 21 (8.4%) men, aged 24-61 , all self-described as White European. Ratio women: men are quite more frequent in the sample reflecting a similar ratio in the prevalence of FM in either gender. On average, the patients who participated in the study had suffered from FM for 7.9 years , and 122 (48.8%) had been granted an invalidity pension. Most of the patients  were taking one or more prescription drugs. More than half of the patients  suffered from some form of psychiatric morbidity assessed with SPPI, mainly depression and anxiety. A group of 21 patients (8.4%) were also diagnosed with PTSD.t = 2.98, df = 248, p < 0.01). Mean and SD scores of the Spanish versions of the instruments used are summarized in Table The distribution of PSPS-Spanish total score  did not differ significantly from a normal symmetric distribution , although there was a slight positive skew. There were no significant differences in scoring between men  and women . However, the subsample of patients with FM and PTSD showed significantly higher scores in PSPS  compared with the subgroup of patients with FM but without PTSD   of the validation study sample were randomly selected. They were asked whether they thought that the test could adequately measure the effects of pain as an assault on the person's life and sense of identity. A total of 95.3% patients (143 out of 150) agreed.r correlation coefficients ranged between 0.68 and 0.86; median = 0.80) , indicating a high degree of internal consistency. Item-total The response to the PSPS-Spanish provided by a random subsample of 75 patients with fibromyalgia  granted an invalidity pension) showed satisfactory temporal stability of the scale over a 1-2 week interval, during which the patients did not change baseline treatment. The test-retest correlation assessed with the intraclass correlation coefficient was 0.78.p < 0.001), supporting the suitability of the data for principal components analysis [The KMO was found to be 0.81, which exceeds the recommended minimum value of 0.60 . Bartletanalysis . A one-canalysis . Resultsr = 0.63, p < 0.001), HADS-anx , pain assessed with PVAS , global function assessed with FIQ , and pain catastrophizing . Total SPSS in the subsample of patients with fibromyalgia and PTSD also show a significant association (p < 0.001) with all the questionnaires having similar Pearson's r values to those of the whole sample: HADS-dep (r = 0.61), HADS-anx (r = 0.55), PVAS (r = 0.44) and pain catastrophizing (r = 0.42). However, PSPS correlation with FIQ is much more important in this subsample (r = 0.63).The total PSPS-Spanish score was significantly associated with all the questionnaires assessed Table : HADS-der = 0.51, p < 0.001), HADS-anx , pain assessed with PVAS  and global function assessed with FIQ .To confirm that pain catastrophizing and mental defeat are different constructs, a partial correlation analysis was performed between PSPS-Spanish and the other scales controlling pain catastrophizing. The PSPS-Spanish score was significantly associated with all the questionnaires assessed, even those controlling pain catastrophizing: HADS-dep . We have included one measure of global function, the FIQ, and PSPS-Spanish correlates with this in a higher range in the subsample of patients with FM that also suffer from PTSD (r = -0.63) than in the whole sample (r = -0.41). This is coherent with other studies that demonstrate MD as a predictor of severity and chronicity in PTSD patients [r = 0.40), suggesting that MD and pain catastrophizing are psychological constructs that are related but distinguishable from each other. This finding is also emphasized because MD measured by PSPS-Spanish is associated with depression, anxiety, pain and global function even controlling pain catastrophizing. One limitation of this study is that we did not assess the questionnaire in several populations, including healthy individuals. As this was undertaken in the original validation study we did not consider it necessary.Similarly to the initial validation study , the pri r = -0.4. This isThe present study indicates that the Spanish version of the measure of MD, the Pain Self-Perception Scale, has good psychometric properties, including high levels of internal consistency and test-retest reliability. The one-factor structure is the same as that was found in the original validation study. MD seems to be more important for global function in patients with FM and with comorbid PTSD. MD and pain catastrophizing are different psychological constructs in patients with FM and also in chronic pain patients in general, as have been previously demonstrated .The authors declare that they have no competing interests.JGC, BR, MG and JVL conceived the study design. YLdH and MA collected the data, JGC and BR conducted the statistical analysis, and all authors interpreted the results, drafted the manuscript, and read and approved the final manuscript.The pre-publication history for this paper can be accessed here:http://www.biomedcentral.com/1471-2474/11/255/prepubBack-translated version of the PSPS-Spanish. This file compares the original English version of the PSPS questionnaire and the back translated version of the PSPS.Click here for file


Many people attending rheumatology clinics use analgesics and non-steroidal anti-inflammatories for persistent musculoskeletal pain. Guidelines for pain management recommend regular and pre-emptive use of analgesics to reduce the impact of pain. Clinical experience indicates that analgesics are often not used in this way. Studies exploring use of analgesics in arthritis have historically measured adherence to such medication. Here we examine patterns of analgesic use and their relationships to pain, self-efficacy and demographic factors.Consecutive patients were approached in a hospital rheumatology out-patient clinic. Pattern of analgesic use was assessed by response to statements such as 'I always take my tablets every day.' Pain and self-efficacy (SE) were measured using the Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) and Arthritis Self-Efficacy Scale (ASES). Influence of factors on pain level and regularity of analgesic use were investigated using linear regression. Differences in pain between those agreeing and disagreeing with statements regarding analgesic use were assessed using t-tests.218 patients (85% of attendees) completed the study. Six (2.8%) patients reported no current pain, 26 (12.3%) slight, 100 (47.4%) moderate, 62 (29.4%) severe and 17 (8.1%) extreme pain. In multiple linear regression self efficacy and regularity of analgesic use were significant (p < 0.01) with lower self efficacy and more regular use of analgesics associated with more pain.Low SE was associated with greater pain: 40 (41.7%) people with low SE reported severe pain versus 22 (18.3%) people with high SE, p < 0.001. Patients in greater pain were significantly more likely to take analgesics regularly; 13 (77%) of those in extreme pain reported always taking their analgesics every day, versus 9 (35%) in slight pain. Many patients, including 46% of those in severe pain, adjusted analgesic use to current pain level. In simple linear regression, pain was the only variable significantly associated with regularity of analgesic use: higher levels of pain corresponded to more regular analgesic use (p = 0.003).Our study confirms that there is a strong inverse relationship between self-efficacy and pain severity. Analgesics are often used irregularly by people with arthritis, including some reporting severe pain. Arthritis is a highly prevalent condition and can lead to physical impairments and psychological morbidity, including depression, anxiety and feelings of helplessness . A long Self-efficacy is defined as an individual's judgement of their capability to carry out a course of action required to achieve a desired goal  and in tOur study was conducted in the outpatient rheumatology clinics of Selly Oak Hospital, Birmingham, which were provided by 11 clinicians. The majority of patients had some form of arthritis; a minority had some form of soft tissue musculoskeletal pain. Patients attending rheumatology clinics suffer mostly from an inflammatory arthritis and commonly endure skeletal pains from a variety of causes, including secondary osteoarthritis and myofacial pains . We chosConsecutive patients with any form of arthritis or pain of least 3 months duration and who were able to speak English were approached. Eligible patients were given an information leaflet and those giving written consent were asked to complete a questionnaire. Data were collected over 4 weeks during February and March 2007. Patients with a shorter history of arthritis were excluded because we wished to study established patterns of analgesic use and we believed that 3 months was a reasonable period for these to develop. Questionnaires were self-completed by 81.2% of patients. One researcher (RB) recorded the responses of those unable to write either due to arthritis affecting their hands or ability to speak but not write English.Patients unable to complete questionnaires during their visit to the clinic were given a reply paid pre-addressed envelope and asked to return it by mail. Those who had not returned their questionnaire within two weeks were sent a reminder and a new questionnaire by mail Figure .Demographic data including gender, age, ethnicity (classified according to the 2001 census)  and duraA series of statements was used to assess patients' pattern of analgesic use. Table  In this It was our aim to investigate how patients managed their analgesics in relation to their pain and related factors such as exercise and sleep. A recent study exploring osteoarthritis patients' management of pain and analgesics found that many patients varied their use of pain killers and were often reluctant to take analgesics unless unable to tolerate the pain . AccordiPatients recorded, on a 6-point Likert scale, whether they agreed (strongly agree = 6) or disagreed (strongly disagree = 1) with each statement. For questions where the more strongly the patient agreed with the statement the less regularly they took their analgesics, e.g. 'I only take a tablet when the pain gets too bad,' the scores were reversed. This allowed high scores for all questions to relate to more regular analgesic use. The scores for the four questions related to regularity of use , slight pain (0.5-1.499), moderate pain (1.5-2.499), severe pain (2.5-3.499) and extreme pain (3.5-4). The pattern of analgesic use at each level of pain was examined. T-Tests were also used to examine the differences in mean pain score between those agreeing and disagreeing with statements regarding analgesic use. As this involved multiple comparisons a more conservative significance level (p < 0.01) was used for these analyses, otherwise p < 0.05 was used. To investigate the relative influence of factors on regularity of analgesic use, simple and multiple regression analyses were undertaken. Firstly, simple regression analyses were undertaken between the predictor variables. A significant relationship was found between age and duration of the disease, but both were retained in the model. Age, gender, ethnicity, duration of disease, severity of pain and self-efficacy were entered simultaneously into the model. Ethnicity was entered as a binary variable (white British or other ethnic group) due to the relatively small number of participants from a minority ethnic group. An analysis of the residuals identified that they were normally distributed, so the assumptions for the model were met. Similar methods were used to investigate the influence of age, gender, ethnicity, duration of disease, regularity of analgesic use and self-efficacy on reported pain.Two hundred and eighteen patients completed questionnaires, providing a response rate of 85% figure . The meaUse of paracetamol (acetaminophen) was reported by 65 (29.8%) of participants; compound analgesics (including paracetamol and codeine) by 111 (50.9%) and NSAIDs by 71 (32.6%).The majority of patients in extreme pain reported always taking their analgesics everyday, falling to less than a third of those in no pain. A large proportion of those in no (current) pain and slight pain reported only taking analgesics when they felt their pain was too severe, a practice less common amongst those in greater pain; yet almost one third of patients in extreme pain still only used analgesics when their pain became 'too bad'. A large proportion of patients with all severities of pain varied how they took their analgesics depending on their level of pain. Patients in slight or no pain were much more likely to only take analgesics regularly during 'bad patches' than those in extreme pain. Details are given in table The proportion of patients reporting taking analgesics before bed increased with the level of pain suffered. There was no distinct pattern in those who took analgesics before exercise. Very few of those in slight or no pain took analgesics before exercise compared with approximately one third of those in moderate and severe pain and one quarter of patients in extreme pain.Patients who reported always taking their analgesics daily had a higher mean pain score than those who did not  corresponded to more regular analgesic use. With multiple linear regression only pain was significantly associated with regularity of analgesic use Table .The degree of pain reported was not associated with age, gender or duration of arthritis, but was significantly associated with self-efficacy, regularity of analgesic use and ethnicity. Greater self-efficacy corresponded to less pain. Patients from ethnic minorities had an average pain score of 12.4 compared to 10.9 p = 0.034) for those of white British ethnicity in simple linear regression , exercise , heat  or a bath or a spa . Forty two (20%) were currently being treated by a physiotherapist and 40 (19%) participants reported using a form of complementary therapy.In this study we have explored the way in which patients attending rheumatology clinics manage their analgesics, and the relationships between pain, self-efficacy and how regularly analgesics are used.Previous studies indicate that patients with RA  and OA  may be tIn our study, a majority of patients  agreed with the statement 'I always take my tablets everyday'. A large proportion of patients, however, varied their use of analgesics depending on their current level of pain; including over a third of people reporting severe pain, who only used their medication on demand, or at times when pain was unbearable. This approach is at odds with recommendations in guidelines for health professionals, in which pre-emptive and regular use of analgesics is recommended in order to prevent breakthrough and movement related pain . Recent Analgesic medication appears to be seen differently to other medications in that purposeful dose restraint is common and often seen as acceptable . PatientA variety of psychosocial factors are known to influence pain severity, which in turn may influence patterns of analgesic use. We found, like others , that pa213.5%) and for regularity of analgesic use (R23.7%) highlight the fact that that other psychological factors may be more influential. Beliefs about pain and analgesics [A measure of self efficacy was included in our analysis. This is a task specific trait  which sealgesics ,39, copialgesics , depressalgesics ,41, anxialgesics  may all Our study was cross-sectional and therefore has important limitations particularly because we do not know whether the patterns of analgesic use and perceived self efficacy, remain stable and whether the correlations reported hold true over time. To achieve a high response rate and generalisability we focused on the factors relating to pain that we were most interested in, such as self-efficacy. However we acknowledge that the investigation of other factors such as depression is important and may be worth further study in the future. We did not assess the psychometric properties of the patterns of analgesic use scale prior to its use in this study. It was not our intention to develop a new scale and to report the properties of this scale. We chose our questions to gain an insight into how patients managed their analgesics on a daily basis. A majority of questionnaires were self-completed (81%) but in 19% of cases (41 participants) a researcher recorded the answers. The most common reason for this was difficulty with writing due to arthritis; only 3 of the 41 participants who were assisted were from an ethnic minority. Considering that 16% of the total study population were from ethnic minorities, problems in participants' ability to write English were not a significant factor in this study and are unlikely to result in any bias. Important strengths of our study were an excellent response rate, use of well validated measures, a heterogeneous population, inclusion of consecutive patients and availability of a researcher to help with clarification when patients were completing questionnaires.We found that self-efficacy, regularity of analgesic use and ethnicity influenced the degree of pain reported by patients. The majority of patients in this hospital outpatient sample (85%) reported moderate or more severe pain. People with greater pain reported more regular analgesic use but a large proportion of patients, including some in severe pain, varied their consumption of analgesics greatly. This may be because of patients' beliefs and concerns about medications. Health professionals who recognise such concerns during consultations may be better able to guide patients and encourage more optimal patterns of analgesic use and promote better function.The authors declare that they have no competing interests.RB was involved in the conception and design of the study, collected data, did statistical analyses and drafted the manuscript. KJ co-supervised the project, was involved in the conception and design of the study, assisted with data analysis and helped revise the manuscript. PJ co-supervised the research, was involved the conception of the research, and helped draft and revise the manuscript. SG was involved in the conception of the study and critically reviewing drafts of the manuscript. This research formed part of RB's undergraduate dissertation. All authors read and approved the final manuscript.The pre-publication history for this paper can be accessed here:


The bisphosphonates are able to relieve pain from metastatic bone disease and, when given intravenously, may promote bone healing of lytic metastases. In this study, the aim was to assess the acute effects of a single 'high-dose' intravenous treatment with pamidronate on pain, mobility, analgesic consumption and quality of life (QOL). Thirty-four normocalcaemic patients with painful progressing bone metastases  received a single intravenous infusion of 120 mg of pamidronate as palliative therapy. No other systemic therapy or drugs known to influence bone metabolism were administered during the study. Patients' subjective response to treatment was assessed weekly with a pain questionnaire recording a composite of pain intensity, mobility, performance status and analgesic consumption. In addition, patients completed the Rotterdam Symptom Check List (RSCL) for measurement of QOL and a mobility questionnaire. The mean reduction in the pain questionnaire score (recorded on at least two occasions) was 25% . Twenty patients (59%) showed a > or = 20% improvement and were classified as responders. The median duration of symptomatic response was 12 (range 4-24 +) weeks. The responding patients showed a reduction in RSCL score (improvement in QOL) from 35% before treatment to 27% at 6 weeks, but no significant improvement was noted in non-responders. Twenty-one patients were retreated with pamidronate when their symptoms deteriorated again. Eight out of 15 responders showed a second reduction in pain score of > or = 20%, but this was not seen in any of the six non-responders. Five patients have remained well with no additional treatment for their disease other than repeat infusions of pamidronate every 3-6 months. Treatment was well tolerated. Eight (24%) experienced fever after the first treatment only, and four had asymptomatic, biochemical evidence of hypocalcaemia. The acute inhibition of osteoclastic bone resorption induced by a single high-dose treatment with pamidronate can provide useful palliation for patients with bone metastases. Responding patients may be retreated as symptoms dictate to good effect. We are currently running a phase III double-blind trial with high-dose pamidronate for progressive painful metastatic bone disease to exclude any placebo effect and observer bias.


Etoricoxib protocol- Preemptive and Postoperative Analgesia (EPPA) Trial, investigating whether preemptive analgesia with cox-2 inhibitors is more efficacious than placebo in patients who receive either laparotomy or thoracotomy.Our objective was to report on the design and essentials of the The study is a 2 × 2 factorial armed, double blinded, bicentric, randomised placebo-controlled trial comparing (a) etoricoxib and (b) placebo in a pre- and postoperative setting. The total observation period is 6 months. According to a power analysis, 120 patients scheduled for abdominal or thoracic surgery will randomly be allocated to either the preemptive or the postoperative treatment group. These two groups are each divided into two arms. Preemptive group patients receive etoricoxib prior to surgery and either etoricoxib again or placebo postoperatively. Postoperative group patients receive placebo prior to surgery and either placebo again or etoricoxib after surgery . The Main Outcome Measure is the cumulative use of morphine within the first 48 hours after surgery . Secondary outcome parameters include a broad range of tests including sensoric perception and genetic polymorphisms.The results of this study will provide information on the analgesic effectiveness of etoricoxib in preemptive analgesia and will give hints on possible preventive effects of persistent pain.NCT00716833 To achieve an adequate postoperative pain therapy is a medical challenge. Acute postoperative pain is followed by persistent pain in 10-50% of individuals after common operations, such as groin hernia repair, breast and thoracic surgery, leg amputation, and coronary artery bypass surgery. Since chronic pain can be severe in about 2-10% of these patients, persistent postsurgical pain represents a major, largely unrecognised clinical problem . PostopePreemptive analgesia has become one of the most promising strategies of pain management . The preSystematic reviews suggest that current preemptive analgetic therapy, e.g. systemic non-steroidal anti-inflammatory drugs (NSAIDs), decreased analgesic consumption but not postoperative pain scores . This efA multimodal approach which combines several agents  and delivery techniques  is currently recognised as best practice in postoperative pain management . TraditiTo our knowledge, there are only a limited number of publications examining the preemptive effect of COX-2-inhibitors on the intensity of postoperative pain. All these studies deal with orthopaedic surgery -23. We tThe study is a 2 × 2 factorial armed, double blinded, randomised placebo-controlled trial comparing (a) etoricoxib and (b) placebo in a pre- and postoperative setting. After randomisation, patients receive preemptive medication of either (a) or (b). Medication will be given postoperatively for additional three days. Additionally, all patients receive morphine administered through Patient Controlled Analgesia (PCA). Analysis of all records is performed by blinded evaluators. The total follow-up period per patient is 6 month. Trial registration is NCT00716833.For the included patients the following criteria must be met:- Age ≥ 18 years- Scheduled abdominal or thoracic surgery harming peritoneum or pleura- ASA classification I or II according to the American Society of AnaesthesiologistsMain exclusion criteria are:- Severe cardiac/pulmonary/renal or neurologic diseases- ASA score > II- Patients with insulin-dependent diabetes mellitus or other diseases influencing the peripheral sensibility - Regional blocks- Continuous use of analgesics- Pregnancy or lactation- Uncontrolled hypertension- Contraindications listed in the product information of etoricoxib, i.e. intolerance, ulcers or gastric bleeding, inflammatory bowel diseases, anaphylactic reactionsInformation will be held on the vigil of surgery. If criteria are appropriate and patients want to participate, they give their written informed consent with sufficient time of consideration.Patients are randomly allocated to either the preemptive or the postoperative treatment group. These two groups are each divided into two arms. Preemptive group patients receive etoricoxib prior to surgery and either etoricoxib again or placebo postoperatively. Postoperative group patients receive placebo prior to surgery and either placebo again or etoricoxib after surgery  is anticipated taking a drop out rate of 10% into account . With tThe calculation of the effective size is based on the data of Sinatra et al. . The autrd year resident in the field of anaesthesiology and specialised pain medicine. They contributed to all medical duties.Participating trial physicians are employees of the Multidisciplinary Pain Centre, Department of Anaesthesiology, University of Munich, Germany. Their average qualification is at least equal to a 3Patients are randomly allocated to either the preemptive or the postoperative treatment group. Preemptive group patients get etoricoxib 120 mg p.o. prior to surgery (day 0). After surgical intervention, depending on their respective allocation, patients receive either etoricoxib 120 mg p.o. or placebo for the next three postoperative days (day 1-3). Postoperative group patients get placebo prior to surgery and continue afterwards with either placebo or etoricoxib 120 mg p.o. for three postoperative days  and according to common guidelines for clinical trials (ICH-GCP). The protocols have been approved by the Ethics Committee, University of Munich and the national component authority . Written informed consent is obtained from all patients.The study is performed according to the principles of the Declaration of Helsinki  within the first 48 hours after surgery (PCA)- Baseline personal situation on the DGSS (German Society for the Study of Pain) validated pain questionnaire , compris- Systematic quantitative sensory testing (QST). The detailed QST protocol including reference data is reported elsewhere . In brieThermal Testing comprising cold and warm detection thresholds , paradoxical heat sensations (PHS) during the thermal sensory limen procedure (TSL) of alternating warm and cold stimuli and cold and heat pain thresholds ;a) Mechanical Testing comprising mechanical detection thresholds (MDT), mechanical pain thresholds (MPT), mechanical pain sensitivity (MPS), dynamic mechanical allodynia (DMA), the wind-up ratio (WUR), vibration detection thresholds (VDT) and pressure pain thresholds (PPT).b) - Pain intensity - Overall morphine consumption- Side effects (documentation according to ICH - GCP Guidelines)- Genetic polymorphisms: the metabolic profile of etoricoxib involves cytochrome P450-dependent hydroxylation and oxidation as primary clearance pathways . DiffereFor time points please refer to Figure Descriptive analysis of the study population  will be made for all parameters.Main outcome measures will be analysed with a 2 × 2 factorial ANOVA. Independent variables are time point of medication uptake and allocated study arm, dependent variable is the cumulative morphine consumption within 48 hours postoperatively.Secondary outcome measures  will be analysed equivalent, taking into account the test interval (repeated measurement ANOVA). ANOVA will be adjusted according to Bonferroni using t-test for post-hoc confirmation of significant alterations.Ordinal scaled data will be analysed with Kruskal Wallis test confirming significance with chi2 test.For analyses of associative coherence we will use Spearman's correlations coefficient, Wilcoxon-test or Kruskal Wallis test. All reports will be performed according intention-to treat analysis.® Software . All data entry will be carried out twice.Data entry is done with SPSS statistical software system . Data analysis will be done with SAS/STATInternal and external audits will be held in order to assure quality standards according to ICH-GCP guidelines, the Declaration of Helsinki and governmental standards.To our knowledge, the EPPA trial is the first clinical study to investigate the preemptive analgesic effect of etoricoxib on the cumulative postoperative morphine consumption applying a 2 × 2 factorial study design. In addition, our protocol takes into account individual sensoric perception of the skin as well as genetically different polymorphisms regarding the drug action.Inclusion and exclusion criteria were deployed pragmatically in order to facilitate screening and recruitment. Exclusion criteria (besides standard items such as pregnancy or contraindications to the study medication) are either disease interfering with the patients' sensory perception or with expected side effects or possible harm related to etoricoxib. Our inclusion and exclusion criteria are based on further trials and according to the summary of product information ,30Several COX-2-inhibitors have been shown to be effective treating postoperative pain -33. DataAdditionally, etoricoxib demonstrated superior safety in gastrointestinal toxicity due to its high selective COX-2 inhibition that is observed with its use. Other NSAID-associated effects, including renal adverse effects, appear to be similar to those of other traditional NSAIDs .The pharmacokinetic evaluation of etoricoxib indicates a moderate rate of absorption and a t1/2 of approximately 20 hours that enables once-daily dosing [We have chosen etoricoxib as verum treatment due to the presented pharmacologic properties such as our own clinical experience dealing with. Drug approval for peri- and postoperative setting has not yet been authorised.Postoperative pain involves not only peripheral mechanisms, most notably the sensitization of nociceptors due to inflammation, but also secondary central mechanisms, including hyperexcitability of nociceptive neurons . TheFrom a clinical perspective, preoperative measurement of sensoric perception may have some predictive value regarding postoperative pain and, therefore, may also predict perioperative analgesic requirement . MartineCYP2C9*1, *2 and *3 occur most frequently with those of a caucasian background [*2 and *3 variant genes is decreased significantly, and carriers of the *3 variant are at risk for complications, such as bleeding after use of warfarin in small amounts [Genetic polymorphisms in P-glycoprotein (P-gp), a membrane-localised transporter codified by the gene MDR1 and Cytochrome P450 (CYP) genes, are involved in drug metabolism and often account for variable drug response or side effects. Some common drugs, including non-steroidal anti-inflammatory drugs, are metabolised by the P450 CYP2 C9 enzyme. There are mostly three variants of CYP2C9 gene which show alternated drug response. The variants  amounts . Newer C amounts . Even thWe have chosen a 2 × 2 factorial design for the following reasons: the factorial design has several important features. Firstly, it has great flexibility for exploring the treatment effects in the trials. Whenever examining treatment variations, factorial designs are strong candidates as the design of choice. Secondly, factorial designs are efficient due to the ability to combine multiple studies into one rather than conducting a series of independent studies. Finally, factorial designs are the only effective way to examine interaction effects ,54.If the primary aim of a trial is to identify useful single treatments, then it could possibly be more cost effective to use a three-arm study than a 2 × 2 factorial design. In this trial, it is of interest to detect the treatment interaction, i.e. the opioid-sparing effect of a non-opioid treatment. The chosen study design has the power to identify such statistically significant differences between etoricoxibe and placebo treatments . While tThis study is a large-scale randomised placebo-controlled trial to evaluate the efficacy of COX-2-inhibitors in preemptive and postsurgical pain therapy. It can be expected to provide new valuable information on clinical and pathophysiological effects in postoperative pain, i.e. a) the analgetic effectiveness of preemptive analgesia and b) its relation to e.g. sensoric perception or genetical predisposition as possible factors leading to persistent (chronic) pain.All authors declare that they have no competing interests and did not receive any honorarium from MSD Sharp and Dome or other partners. The investigator-initiated grant received by MSD Sharp and Dome guarantees independent conceivability of the study design, its coordination, realisation and independent report of the study results.JF participated in the study design, patient recruitment and trial coordination, and drafted the manuscript. SK, LL and PML conceived of the workflow and acted as trial physicians. BH, HP, PC, MS, TM, PML and GS participated in the design of the study. PC, MS and TM coordinated the study in their departments. MO performed the sample size estimation and conceived of the biometrical study design. DI is the principal investigator and initiator of the study, obtained funding, designed the study and supervised and participated in writing the manuscript. All authors read, and approved the final manuscript.


This study tested the hypothesis that baseline ratings of fatigue/tiredness would be negatively associated with the efficacy of duloxetine on measures of pain and functional ability in patients with fibromyalgia.A post hoc analysis of pooled data from 4 double-blind, placebo-controlled studies of duloxetine in fibromyalgia was performed. The fibromyalgia impact questionnaire (FIQ) tiredness item score  was used to define tiredness subgroups. Patients were stratified into 3 subgroups: mild (0 to 3), moderate (4 to 6), and severe (7 to 10) tiredness. Analysis of covariance models and logistic regressions were used to test treatment-by-tiredness subgroup interactions.Data from the first 3 months are included in this post hoc analysis . At baseline, the distribution of tiredness severity in the duloxetine and placebo groups respectively was 3.64% and 3.75% mild, 16.71% and 15.57% moderate, and 79.65% and 80.68% severe. Rates of clinically significant (≥30% and ≥50%) improvement in brief pain inventory (BPI) average pain were similar across the tiredness subgroups. Tiredness severity at baseline was not negatively associated with the effects of duloxetine on patients' reports of functional ability using the FIQ total score, FIQ measures of physical impairment, interference with work, pain, stiffness, and depression and the medical outcomes study short form-36 (SF-36).Studies of duloxetine in fibromyalgia have demonstrated clinically significant improvements in pain and functional ability . This post hoc analysis of data shows that the efficacy of duloxetine among patients with fibromyalgia does not vary as a function of baseline ratings of fatigue/tiredness. Fibromyalgia is a disorder that is found in approximately 2% of the general population and is characterized by chronic widespread pain and tenderness . AdditioDuloxetine, a potent reuptake inhibitor of serotonin and norepinephrine, was approved in the USA for the management of fibromyalgia in June 2008. Preclinical models of central sensitization suggest that duloxetine is efficacious in the treatment of patients with persistent/chronic pain. In rodents, duloxetine has demonstrated efficacy in the formalin and capsaicin models of persistent pain, as well as in the partial sciatic nerve ligation and L5/L6 spinal nerve ligation models of neuropathic pain ,5. DuloxPatients with fibromyalgia frequently report moderate to severe fatigue and the prevalence of fatigue in patients with fibromyalgia (76%) is almost double that of patients with osteoarthritis or rheumatoid arthritis (41%) ,13. An eThis study comprised a pooled analysis of four double-blind, placebo-controlled, randomized, multicenter clinical trials of duloxetine in patients with fibromyalgia. These studies were conducted in accordance with the ethical principles that have their origin in the Declaration of Helsinki and that are consistent with good clinical practices and the applicable laws and regulations. Table Included patients were at least 18 years of age and met the criteria for fibromyalgia as defined by the American College of Rheumatology. In study 1, patients were required to indicate a pain score of at least 4 on the FIQ pain item  . In studAll four studies assessed the effects of duloxetine and placebo on the BPI average pain score, the FIQ  to 80 (maximum impact)), the patient global impressions of improvement  to 7 (very much worse)), and the medical outcomes study short form-36 .The raw scores for the FIQ tiredness item range from 0 to 10 . In the Treatment-emergent adverse events (TEAEs), collected at every visit by spontaneous reporting from the patient, within the three subgroups were also evaluated. A TEAE was any reported event that first occurred or worsened in severity during treatment, compared with the predefined baseline period.n = 79) with at least one nonmissing postbaseline assessment were included in the efficacy analyses.All randomized patients  or Fisher's exact test. Treatment effects were tested at a two-sided significance level of 0.05. Interaction effects were tested at a two-sided significance level of 0.1. The term 'significant' indicates statistical significance throughout the manuscript.Across all studies, 797 patients received duloxetine and 535 patients received placebo for approximately three months. There were no significant differences between duloxetine-treated and placebo-treated patients in any of the patients' demographic variables. The mean age of patients was 50.2 years ; the majority of patients were female  and Caucasian .At baseline, the distribution of tiredness severity in the duloxetine group (based on the FIQ tiredness item score) was 3.64% (n = 29) mild (0 to 3), 16.71% (n = 133) moderate (4 to 6), and 79.65% (n = 634) severe (7 to 10); the distribution in the placebo group was 3.75% (n = 20) mild, 15.57% (n = 83) moderate, and 80.68% (n = 430) severe. Within the duloxetine and placebo groups, the mean baseline FIQ tiredness scores in the mild subgroup were 2.5 and 2.7, respectively, in the moderate subgroup was 5.3 (duloxetine and placebo), and in the severe subgroup were 8.6 and 8.7, respectively.P < 0.001) in the number of patients with 30% or greater and 50% or greater reductions in the BPI average pain response  in the mean change from baseline to endpoint between the duloxetine and placebo groups  in the mean change (standard error (SE)) from baseline to endpoint between the duloxetine (-2.1 (0.1)) and placebo (-1.4 (0.1)) groups . The number of patients with 50% improvement in tiredness at endpoint was 173 (22.8%) in the duloxetine group and 93 (18.0%) in the placebo group (P = 0.042). No significant differences were observed between the duloxetine and placebo groups in the number of patients with 30% worsening in tiredness at endpoint , placebo, n = 41 (7.9%); P = 0.917) or in the number of patients with 50% worsening in tiredness at endpoint , placebo, n = 27 (5.2%); P = 0.542).The number of patients with 30% improvement in tiredness at endpoint was 257 (33.9%) in the duloxetine group and 150 (29.0%) in the placebo group (n = 233 (38.26%); placebo, n = 87 (21.07%); P < 0.001), and moderate tiredness subgroup ; placebo, n = 18 (21.95%); P = 0.044). This difference was not found in the mild tiredness subgroup , placebo, n = 7 (36.84%); P = 0.373).We found differences between the duloxetine-treated and placebo-treated patients in the frequencies of PGI-Improvement scores of 1 or 2 (patients feeling very much better or much better) across two of the three tiredness subgroups. There were significantly greater numbers of patients in the duloxetine, compared with the control group, who reported global positive improvements in both the severe tiredness subgroup  in the mean change of the SF-36 scores from baseline to endpoint between the duloxetine and placebo groups on the health outcome measures of the SF-36 mental component summary; bodily pain, general health, mental health, physical functioning, role-emotional, role-physical, social functioning, and vitality . For the FIQ pain score, there was no significant therapy-by-tiredness subgroup interaction (P = 0.74). The effect of duloxetine on the FIQ total score, physical impairment score, interference with work score, pain score, tiredness score, rested score, stiffness score, and depression score was consistent across patients with mild, moderate, or severe tiredness (P > 0.1 for treatment-by-tiredness subgroup interaction). No significant therapy-by-tiredness subgroup interaction in the PGI-Improvement score was observed among the three tiredness subgroups (P = 0.908). The effects of duloxetine on the health outcome measures of the SF-36 mental component summary, physical component summary, bodily pain, general health, mental health, physical functioning, role-emotional, role-physical, social functioning, and vitality were consistent across patients with mild, moderate, or severe tiredness (P > 0.1 for treatment-by-tiredness subgroup interaction).The effect of duloxetine on the BPI average pain score was consistent across patients with mild, moderate, or severe tiredness (P < 0.1) treatment-by-tiredness interaction in the percentage of patients with one TEAE or more was observed. Significant treatment-by-tiredness interactions were found for the percentage of patients with the following TEAEs: hypoaesthesia, arthralgia, cough, myalgia, bronchitis, influenza, palpitations, restless leg syndrome, and osteoarthritis (Table P > 0.1) in the percentage of patients with nausea. Comprehensive pooled safety analyses for these four studies have been performed and previously reported [A significant  of the patients treated with duloxetine had a 30% or greater reduction in BPI average pain, and 35.3% of patients had a 50% or greater reduction in pain . Among pSeveral double-blind, placebo-controlled studies have shown that duloxetine, compared with placebo, more frequently produces clinically-significant improvements in pain and functional ability -11. A poIn the pooled analysis of four placebo-controlled trials in patients with fibromyalgia reported here, the efficacy of duloxetine did not vary as a function of baseline ratings of tiredness, as defined by the FIQ tiredness rating.At baseline, the distribution of tiredness severity in the duloxetine and placebo groups were less than 4% of patients in the mild subgroup and more than 90% of total patients in the moderate to severe subgroups. This is not surprising, as a previous study has reported that up to 90% of patients with fibromyalgia report moderate to severe fatigue levels .The rates of clinically significant (≥30% and ≥50%) improvement in BPI average pain were similar across the three tiredness subgroups, demonstrating that the efficacy of duloxetine in the treatment of pain in patients with fibromyalgia is not associated with baseline tiredness levels.Analyses of the PGI-Improvement produced findings similar to those for BPI average pain ratings. As with the other efficacy measures reported here, there was no significant therapy-by-tiredness subgroup interaction on the measure of PGI-Improvement. Baseline tiredness levels were not significantly associated with the effects of duloxetine on the patients' reports of functional ability using the FIQ total score and the FIQ measures of physical impairment, interference with work, pain, stiffness, depression and the SF-36 mental and physical component summary scores, bodily pain, general health, mental health, physical functioning, role-emotional, role-physical, social functioning, and vitality.Some limitations of this work should be considered. The results are based on four acute treatment trials of 12 weeks and the results may not generalize to a longer duration of treatment. In addition, sleep and fatigue/tiredness may have a correlation. Future studies should measure sleep quality and its effect on fatigue/tiredness in the fibromyalgia population. The results of these studies may not generalize to individuals with fibromyalgia symptoms diagnosed with Diagnostic and Statistical Manual of Mental Disorders-IV axis-one psychiatric disorder, rheumatic disease, or treatment-resistant patients, because such patients were excluded from the studies. Most of the patients included in these studies were middle-aged Caucasian women, which may limit generalization of these results to men and other individuals with fibromyalgia. The FIQ tiredness item is used to substitute the formal measure of fatigue, because the formal fatigue measure was not used in all four of the fibromyalgia studies. The FIQ tiredness item may not capture all aspects of fatigue as a formal fatigue scale would. It is worth noting that question number 20 of the Beck depression inventory refers to fatigue and tiredness interchangeably. Lastly, the distribution of patients in the tiredness subgroups was skewed due to the large number of patients in the severe subgroup (up to 81%) compared with the moderate (up to 17%) and the mild (<4%) subgroups; therefore, the information on patients in the mild and moderate subgroups may not be as robust as that in the severe subgroup.This pooled analysis of four randomized placebo-controlled studies provides evidence that the efficacy of duloxetine on pain does not vary as a function of patients' baseline ratings of tiredness, thus implying that baseline tiredness may not need to be factored into models of efficacy regarding pain.BPI: brief pain inventory; FIQ: fibromyalgia impact questionnaire; PGI-Improvement: patient global impressions of improvement; SE: standard error; SF-36: medical outcomes study short form-36; TEAE: treatment-emergent adverse events.Journal of Musculoskeletal Pain and receives from the publisher a royalty for his work in that capacity. He is a member of the International MYOPAIN Society Board (non-remunerative position). Dr. Russell has never owned a pharmaceutical company, or owned stock in a pharmaceutical company that he is aware of, or worked as an employee for a pharmaceutical company. Dr Moldofsky is the principal investigator at a research site, the Toronto Psychiatric Research Foundation, a not for profit corporation that has received funds for participating in a research study, which is sponsored by Eli Lilly and Company. Dr. Moldofsky has received research support from Eli Lilly, Krele, Pfizer, Pierre Fabre, Sanofi Aventis, and Schering Plough; has acted as a consultant for Boehringer Ingleheim, Eli Lilly, Jazz Pharmaceuticals, Krele, Lundbeck, Merck, Paladin Labs, Pfizer, Pierre Fabre, Sanofi Aventis, Schering Plough, and Valeant; and was on the speaker's bureau for Pfizer. Drs Wohlreich, Chappell, Wang, and D'Souza are employees and stockholders of Eli Lilly and Company.Dr Bradley is a consultant for Eli Lilly, Pfizer, and Forest; has received grant/research support from the National Institutes of Health, the Agency for Healthcare Research and Quality, Eli Lilly, Pfizer, and the American Fibromyalgia Syndrome Association; has received honoraria from Eli Lilly, Pfizer, Forest, and the Society for Women's Health Research; is a member of the speakers/advisory board for Eli Lilly and Company; and has received royalties from UpToDate Rheumatology. Dr Bennett is on advisory boards for Eli Lilly and Company, Schwarz, Jazz and Pfizer. Dr. Russell has received honorarium as a consultant and speaker for Pfizer, Eli Lilly and Company, Jazz, Forest Laboratories, and Grunenthal, and as a consultant for Allergan. He has received honorarium for being a speaker on the medical advisory board for Pfizer, Eli Lilly and Company, Jazz, Pierre Fabre, Nicox, Daiichii Sankyo, and Ortho McNeil Jannssen. He has received funding as a principal investigator for Pfizer, as a local principal local investigator for Eli Lilly and Company, Allergan, and Schwarz/UCB, and as a lead investigator for Jazz, Grunenthal, and Autoimmune Technologies. Dr. Russell is the editor of the Each of the authors listed have made substantive intellectual contributions to this study. LB, RB, IJR, MMW, ASC, FW, DND, and HM have made substantial contributions to analysis and interpretation of data, have been involved in drafting the manuscript and/or revising it critically for important intellectual content and have given final approval of the version to be published.


Objective: Adequate control of postoperative pain directly improves patient satisfaction and outcomes, and timely identification of patients with poorly controlled pain is essential. Pain management protocols are best studied in patients recovering from the same operation. In our institution, the postoperative pain regimen for patients undergoing deep inferior epigastric perforator (DIEP) flap breast reconstruction is standardized using patient-controlled analgesia (PCA) followed by conversion to oral narcotics. From this uniform population, we were able to identify a subgroup of patients with poor pain control. Methods: Over a 44-month period, 179 consecutive patients underwent DIEP flap breast reconstruction with 242 flaps performed. A retrospective chart review recorded PCA usage, visual analog scale pain scores, and length of stay. Results: Pain management with PCA after DIEP flap breast reconstruction was uniformly controlled. Most patients (74.9%) required PCA usage in the first 2 days with conversion to oral analgesics. A subgroup of patients (25.1%) continued to require PCA usage on the third postoperative day. These “nonresponder” patients had a higher visual analog scale score on the first postoperative day, higher total intravenous morphine use, and a longer length of stay . A multivariate analysis revealed more nonresponders among patients undergoing immediate breast reconstruction (P < .05); however, all other factors analyzed had no correlation. Conclusion: We report a subgroup of patients with poor pain control after DIEP flap breast reconstruction. This group of patients required a longer course of pain management and subsequently a longer hospital stay. Pain management protocols that identify these patients promptly can allow for appropriate modifications. The proper management of postoperative pain is important in both aesthetic and reconstructive surgery. It has been shown that when pain is well-controlled, outcomes are improved in orthopedic, vascular, general, and cardiac surgery.Evaluation of pain management protocols can be confounded by differences in populations chosen for study. Ideally, postoperative pain should be assessed in comparable subjects undergoing similar, if not identical, operations. Previous studies have shown that patients with DIEP flap have significantly less morphine use and shorter hospitalizations than those with musculocutaneous flap for breast reconstruction.The acute pain literature describes a population of patients that have a poor response to narcotic use in both cancer and postsurgical care. These patients represent 25% to 40% of the population and have been previously described as “nonresponders.”We evaluated narcotic use and postoperative pain control in patients with DIEP flap breast reconstruction within a standardized pathway. We used the visual analog score (VAS) score to assess postoperative pain. The VAS score has been shown to reliably assess acute pain and changes in pain intensity.Over a 44-month period, all patients who underwent autologous breast reconstruction were identified. All patients had a DIEP flap reconstruction, as superficial inferior epigastric artery (SIEA), free transverse rectus abdominis musculocutaneous (TRAM), muscle-sparing free TRAM, and pedicled TRAM flaps were excluded. Details of the operative technique were standardized including the internal mammary recipient vessel site as well as the abdominal closure; no patients in this series required abdominal mesh placement.A retrospective chart review of the clinical course, postoperative PCA usage, VAS pain scores, and length of stay was performed. The VAS score was recorded as a daily average. Patients were excluded if there was a return to the operating room, as this altered the standardized pain control regimen. Patients were evaluated the morning of the POD 3 for conversion to oral narcotics. Criteria for conversion to an oral regimen were based on a low overnight VAS score with minimal overnight PCA morphine usage.A detailed database was reviewed, and data collection included patient demographics, body mass index (BMI), Breast Cancer susceptibility gene (BRCA) status, previous radiation, previous chemotherapy, immediate/delayed reconstruction, unilateral/bilateral, flap weight, mastectomy weight, recipient vessel, number of perforators, and microvascular flap complications.U test. Comparisons of incidences were performed using a Fisher exact test. Univariate analysis of factors associated with nonresponders was performed; all factors that were found to be significant to the P ≤ .25 level were included in multiple logistic regression analyses. Multiple logistic regression with nonresponder status as the dependent variable was performed using backwards stepwise elimination with elimination significance set to .10. Statistical significance was determined at P ≤ .05.Patients were categorized as responders if they were successfully weaned from PCA opioids to oral pain medications by the POD 3. Comparisons of intravenous (IV) morphine requirements, VAS scores, and length of stay were analyzed by using the Mann-Whitney The study was approved by the institutional review board at Beth Israel Deaconess Medical Center.Over a 44-month period, 179 consecutive patients underwent DIEP flap breast reconstruction with a total of 242 flaps performed. All patients received PCA in the first 3 PODs: 133 patients received morphine and 46 patients received hydromorphone. The hydromorphone dose was converted to morphine with a 5-to-1 conversion.8p < 0.05)    Fig  and a lo5) Table  than theP < 0.05). This resulted in a positive predictive value of 39% and a negative predictive value of 81%.We also found a relationship between the VAS score on POD 1 and the total IV morphine consumption Fig . A higheP < .05). There were no other correlations for age, BMI, BRCA status, a previous history of radiation or chemotherapy, mastectomy weight, flap weight, and unilateral versus bilateral reconstruction  gene which could explain the interindividual differences in pain control by opiate analgesia.10Stamer et alStamer et al11Our study revealed that a nonresponder could be predicted on the POD 1 by a significantly higher VAS score. Previous studies were able to identify 89.2% of the nonresponders based on the size of the loading dose and the pain scores in the first 30 minutes after surgery.13P < .05).The ability to predict the nonresponder patients in the POD 1 is extremely important. As the nonresponder group consumes higher total morphine amounts, they experience poor pain control at the same time. Reducing the opioid dose has been shown to decrease the opioid-related side effects .-19With early detection of nonresponders, we can potentially improve postoperative pain management by combining different types of systemic analgesics. The major benefit of multimodal analgesia may be a decrease in the incidence of opioid side effects rather than an increase in the effectiveness of pain control.16Our study has several limitations. As our postoperative pain data was collected using IV PCA, it is not clear how pain is comparably controlled on oral pain medications. It would be important to determine whether a similar nonresponder group exists for oral opioids. With the shift of many plastic surgery procedures to an outpatient setting, identification and intervention in this subset of patients could potentially improve postoperative care on a wider scale. Another limitation is the psychological response to postoperative pain. As there are emotional and learned responses to pain, further collaborations are necessary to evaluate these associated psychological components.The last limitation is that there are minute technical differences even among DIEP flap reconstruction patients. As the amount of muscle dissection and nerve damage can be variable based on the anatomy, this can affect postoperative pain. Our study did not find associations between number of perforators used and pain; however, nerve damage and injury can be difficult to quantify and can certainly contribute to postoperative pain.The presence of a nonresponder group is important in any postsurgical setting. As opioid receptor characteristics are universal, recognition of this subgroup is critical and not confined to one type of surgery.Our study identifies a group of patients who have a poor response to standardized pain control regimens after a DIEP flap breast reconstruction. This group of nonresponders requires more IV PCA morphine and has a longer length of stay. We can identify these patients on the basis of the VAS score on the POD 1 and can potentially alter their pain management and improve patient outcomes. We hope to design future prospective trials to address this group.


The objectives of this study were to investigate if the predictive value of this set of variables could be reproduced among chiropractic patients in Finland, and if the model could be improved by adding some new potential predictor variables.In a previous Swedish study it was shown that it is possible to predict which chiropractic patients with persistent LBP will nd and 4th visits using standardized questionnaires on new patients with LBP and/or radiating leg pain. Status at base-line was identified in relation to pain and disability, at the 2nd visit in relation to disability, and "definitely better" at the 4th visit in relation to a global assessment. The Swedish questionnaire was used including three new questions on general health, pain in other parts of the spine, and body mass index.The study was a multi-centre prospective outcome study with internal control groups, carried out in private chiropractic practices in Finland. Chiropractors collected data at the 1st, 2nd visit (yes/no) and BMI  was also identified with similar predictive values. Common throughout the testing of various models was that improvement at the 2nd visit had an odds ratio of approximately 5. Additional analyses revealed a dose-response in that 84% of those patients who fulfilled none of these (bad) criteria were classified as "definitely better" at the 4th visit, vs. 75%, 60% and 34% of those who fulfilled 1, 2 or all 3 of the criteria, respectively.The Swedish model was reproduced in this study sample. An alternative model including leg pain (yes/no), improvement at 2nd visit. The number of predictors is also important.When treating patients with LBP, at the first visits, the treatment strategy should be different for overweight/obese patients with leg pain as it should be for all patients who fail to improve by the 2 The causes of non-specific low-back pain (LBP) are largely unknown ,2. ObvioChiropractors in the Nordic countries use predominantly spinal manipulative therapy (SMT) in their treatment of back problems, frequently in combination with soft tissue therapy, advice on exercise, ergonomic precautions, and lifestyle changes -5. Randonot report definite improvement early in the course of treatment, making it possible to exclude from treatment those who are unlikely to become LBP-free.Until recently it has not been documented which patients with LBP are most likely to benefit from the chiropractic approach. However, the predictive value of a set of clinical observations has been previously studied in patients with LBP receiving chiropractic care -10. Thisth visit was noted to be a predictor for outcome 3 and 12 months later [Furthermore, early recovery at the 4hs later  and the hs later .th visit [th visit (96%), it could only predict 19% of patients who would be "definitely better".Specifically, in a Swedish study of patients with LBP, it was shown that patients with LBP for altogether at least 30 days in the past year, who had leg pain, and who did not report some improvement by the second treatment, were not good candidates for definite improvement by the 4th visit . AlthougThe objectives of the present study were to investigate if similar findings could be reproduced in a different cultural setting (Finland), and if the model could be improved by adding a few more potential predictors.The study was designed as a multi-centre clinic-based prospective outcome study with internal control groups, using standardised questionnaires, conducted in private chiropractic practices in Finland.A steering group was established, consisting of five researchers and one research officer, supervised by an experienced researcher. Questionnaires from the previous Swedish study were used by permission, translated and culturally adapted in a pilot-study involving 30 patients for face validity.Based on clinical intuition, three variables were added to this questionnaire. These were weight/height (body mass index-BMI), general health, and pain in other parts of the spine.All members of the Finnish Chiropractic Union were invited to participate in the study to collect data from a maximum of 40 patients each. The steering group members instructed and assisted the involved chiropractors using a method previously described by a Swedish research group , with onConsenting patients were included after receiving information on the purpose of the study by their chiropractor. Inclusion criteria were new patients with LBP with or without leg pain and patients had to return at least once following the first visit.th treatment visit. Only the treating chiropractor knew the identity of the participating patients. The regional scientific ethics committee reviewed and defined this study as a quality assurance project, which does not require committee approval.Clinician and patient anonymity was ensured by using codes, tying the patient to the treating chiropractor. This code was destroyed after the 4Information for the study was collected by the chiropractors on the first, second, and fourth visits [Additional files nd visitbetter at 2. Another new variable (number of disabilities) was created by counting the number of positive answers to these questions . Three new items: BMI, general health, and pain in other parts of the spine, were also included in the questionnaire.All potential predictors but three were taken from the previous Swedish study , consistnd and 4th visit, and type of treatment provided at the first visit was also collected to describe the patients and the clinical procedure. Also these questions were taken from the previous Swedish study [Severity of pain was reported at all three times to enable comparisons over time, using a five point scale ranging from unbearable to pain free. Another of the descriptive variables was unsuitable reactions. A local pain reaction after the first treatment was defined as "unsuitable" if it was reported to have lasted for longer than 24 hrs, or if it consisted of new radiating pain (regardless duration), according to standardized answers, based on information from two previous descriptive studies of Norwegian and Swedish patients who received chiropractic treatment [Information on time since last treatment, both at the 2sh study . Severitreatment ,12.In addition, reactions described as free text under "other" were individually scrutinized for unsuitable reactions.th visit) was defined as positive only for those patients who reported to be definitely better at the fourth visit (or at the last visit if treatment was ended before the fourth visit). Missing data for this variable were interpreted as not being definitely better, i.e. a form of worst case interpretation was used.The outcome . In the first, we used the same variables as those found to be significant in the previous Swedish study, to see if their results could be reproduced in the present study sample. These variables were For each model, odds ratios with their 95% confidence intervals were calculated as well as the sensitivity, specificity, numbers correctly classified, and area under the Receiver Operator Characteristic curve. A Receiver Operator Characteristic value of 50% indicates chance findings, whereas a minimal value of at least 70%, arbitrarily, is considered to be acceptable, and a value of 100% indicates perfection. In all analyses, adjustment was made for clustering, to counteract the undue effect single clinicians could have on the results.At baseline, all 47 eligible chiropractors in the Finnish Chiropractic Union were invited to participate in the study to include 40 patients each. The maximum possible amount of patients was 1880. Thirty-three chiropractors participated, which means that the optimal amount of patients was 1320. These chiropractors returned complete sets of questionnaires from 1023 patients. From the 1023 returned questionnaires, 13 were discarded due to incorrect coding and a further 22 were discarded due to missing relevant baseline data and 4 because they appeared to belong to patients who had neither LBP nor leg pain. Occasionally, some data were missing for the various variables.The base-line sample has been described in Table duration of pain at base-line, constant/not constant pain at base-line, and duration of pain in the past year [Figure At base-line, 98% had LBP and almost half had leg pain. Pain was most commonly reported as moderate (45%) or severe (29%), and 63% had experienced pain for at least 2 weeks. At the time of consultation, the nature of the pain was described as constant by 65% and a little more than half had experienced the pain for altogether at least more than 30 days in the past year. The spread of data is shown for the various combinations of the three variables r Figure .number of disabilities out of 5 possible, with pain getting up from sitting being most common (70%), followed by pain putting on socks/shoes (66%), and pain on walking (54%).Sixty-nine percent reported between 2 and 4 painful Almost all reported to have excellent or good general health, and 25% reported altogether at least 30 days of pain in the neck or mid back in the past year. The group was almost equally distributed between underweight/normal weight and overweight/obese. Two-thirds reported to feel immediately better after the 1st treatment.As can be seen in Table The most commonly reported intensity of pain was now mild (45%) or moderate (28%) and 85% reported to have experienced no "unsuitable reaction". Fifty-seven percent reported to have improved in at least one "disability" aspect .The most commonly reported duration since the first visit was maximum 2 weeks (42%). The intensity of pain was now even more reduced, most commonly reported as none (42%) or mild (31%).Two-thirds reported to be definitely better, 20% reported to be less than definitely better whereas the outcome was unknown for 14%. The latter group was classified as not definitely better [Table th visit: Leg pain, duration of pain at base-line, total duration of pain in the past year, general health, other spinal pain in the past year, BMI, immediate improvement and nd visitbetter at the 2.The following variables were positively associated with definite improvement at the 4Sex, age, severity of pain at base-line, constant pain at base-line, pain turning in bed, problems sleeping, problems putting on socks/shoes, pain on walking, pain on getting up from sitting, and number of "disabilities".Consequently, there were no significant associations for the following variables: leg pain, duration of pain in the past year, and nd visitbetter at the 2, when tested on our data obtained a sensitivity of 41%, a specificity of 87%, and numbers correctly classified were 71.5%. The area under the Receiver Operator Characteristic curve was 72%.As can be seen in Table The full Swedish model including the five variables, which in the present study were significantly associated with the outcome, did not result in better values.better at 2nd visit. It had a somewhat higher sensitivity and lower specificity but there was almost no change in the number classified and area under Receiver Operator Characteristic curve [Figure The final minimal model, based on the variables previously used in the Swedish study, consisted of only one variable, BMI, general health, and spinal pain, were added to the full model as described above [Table BMI was retained in the final model together with leg pain and nd visitbetter at 2.The three new variables, ve Table . Again tnd visit better at the 2in relation to outcome had the strongest odds ratio with estimates between 4.7 and 5.0. For detailed information, see Table th visit, whereas this is the case only for 50% of those who are not better by the second visit.In all models, type of treatment at the first visit  would have an observable effect on the outcome variable, or improvement at the 2nd visit, but no such findings emerged (data not shown).Three additional exploratory analyses were undertaken. First, in order to see if the duration since the 1st visit (at the 4th visit) was of any relevance for the outcome. This variable was therefore categorized into 1–14 days, 14–28 days, and one month or more and forced into the final Finnish model. However, it was not significantly associated with outcome and its presence did not significantly alter the estimates in the model (data not shown).Second, an attempt was made to see if nd visitleg pain, not better at 2, and overweight/obese) were checked for a dose-response, in relation to being definitely improved at the 4th visit. With none of these findings, 84% would be definitely better at the 4th visit, whereas the corresponding figures for one, two, respectively three of these findings were 75%, 60% and 34%. The data have been presented also as odds ratios in Table Finally, a logistic regression was undertaken in which the 3 variables that remained in the final model  is a predictor for the outcome at both 3 and 12 months, at least in patients with relatively long-lasting or recurrent LBP .When the previously achieved best Swedish model was applied to patients from Finland, the associations between outcome and the three relevant variables  were again positive, although duration failed to reach significance and leg pain was only weakly associated, and in the final analysis, only improvement at the second visit remained significant with an odds ratio of 4.9.Improvement at the second visit meant that patients reported that at least one of the five "disabilities" was better than at base-line, namely sleeping, turning in bed, putting on socks/shoes, getting up from a chair, or walking.Even when adding the three new factors , improvement at the second visit was the only strongly associated variable that emerged from the multivariate analysis, still with an odds ratio of 5.number of these predictor variables present in each person was tested against outcome, a dose-response was revealed. In the whole study sample, the proportion of patients in the study who were "definitely better" at the fourth visit was 66%. In patients with none of these three predictors, 84% were better, whereas only 34% of those who had all three belonged to this category.In the final analysis, taking into account also leg pain and BMI did not really improve the estimates in a clinically meaningful way. However, when the Obviously, it is important to keep in mind the weaknesses in this type of study design, such as several possibilities for bias in relation to selection of practitioners and patients, in relation to their expectations of treatment outcome, and in relation to the recording of outcome, such as there being a tendency to "inflate" the result by the chiropractor in questionnaire studies like this one and patients providing polite positive answers. To counteract the latter possibility, patients were not considered improved unless they had stated that they were "definitely" improved. Also, clinicians were informed that the purpose of the study was to study differences between patients who react differently to the treatment, to counteract any desire to "prove" a high success rate. It was also impossible to define the exact nature of "leg pain" due to the brief questionnaire.Clinical studies frequently investigate outcome by a large number of research tools, such as visual analogue scales indicating level of pain and disability questionnaires. Also, it is considered important that outcome data are collected by people who are independent to the treatment procedure, or at least using self-report questionnaires. However, when considering the feasibility of this type of study, one has to balance the negative aspects with the present approach (i.e. the risk of reporting bias and the inconvenience of brief outcome measures) against its positive aspects . In our study group, we are depending on clinicians to participate in their normal clinical context, without financial compensation for time lost due to lengthy procedures, which obviously requires the use of a very short questionnaire. Also, most private practitioners probably use and relate well to our outcome measure "definitely better", which makes the results of our study more easily applicable in clinical practice.The reader should also be aware of the fact that with no control group, these outcome data cannot be regarded as estimates of treatment effect. The purpose of the study is instead to study the effect that various factors seem to have on the outcome, bearing in mind that the predictors tested in this study possibly could give similar results in patients who are treated with other therapies or perhaps even in those who receive no treatment at all. Obviously this would have to be tested in randomised controlled clinical trials. Interesting future research areas would also be to study the effect of various management strategies (e.g. frequent vs. less frequent treatments) and to investigate also the effect on outcome of different various psychological profiles.Strengths in this study are the large study sample, and the good quality of the data. There were only few obviously faulty questionnaires and only few missing data. Positive aspects of this type of study are that it documents the normal clinical situation and that it includes a wide variety of practitioners and patients. Secondary gains are that it makes chiropractors able to participate in research without having to spend too much time with the project, makes them aware of the rigours associated with data collection, encourages an interest in the study results, and hopefully, makes research results more clinically relevant for those who participated in data collection. Although this study design requires a simplistic approach to data collection, it is a relatively cheap way to collect clinically relevant information on a large number of patients.nd visit has a poor short-term prognosis. Therefore, when treating patients with LBP, the treatment strategy should be different for overweight/obese patients with leg pain as it should be for all patients who fail to improve by the 2nd and 4th visits.There are three important messages in this report. First, already at the first visit one should be vigilant with overweight/obese patients who have pain radiating into the leg. Second, at the return visit, for these patients if there is lack of improvement, the short-term prognosis is poor. Third, that any patient, who fails to improve at the 2The authors declare that they have no competing interests.SM was responsible for planning and executing the study, participated in the data collection and drafted the manuscript. CLY supervised the process. Both SM and CLY participated in the design of the study and performed the analysis together with NW. NW was responsible for the statistical analysis. TA, OA, KE, MT and HP participated in the design of the study and the data collection. All authors read, finalized and approved the final manuscript.Baseline questionnaire for Finnish predictor study (pdf). Finnish distributed questionnaire followed by an English translation.Click here for fileReturn questionnaire for Finish predictor study (pdf). Finnish distributed questionnaire followed by an English translation.Click here for fileth visit questionnaire for Finnish predictor study (pdf). Finnish distributed questionnaire followed by an English translation.4Click here for file


Comorbid psychopathology is an important predictor of poor outcome for many types of treatments for back or neck pain. But it is unknown if this applies to the results of medial branch blocks (MBBs) for chronic low back or neck pain, which involves injecting the medial branch of the dorsal ramus nerves that innervate the facet joints. The objective of this study was to determine whether high levels of psychopathology are predictive of pain relief after MBB injections in the lumbar or cervical spine.Low, Moderate, or High levels of psychopathology. The primary outcome measure was the percent improvement in average daily pain rating one-month following an injection. Analysis of variance and chi-square were used to analyze the analgesia and functional rating differences between groups, and to perform a responder analysis.This was a prospective cohort study. Consecutive patients in a pain medicine practice undergoing MBBs of the lumbar or cervical facets with corticosteroids were recruited to participate. Subjects were selected for a MBB based on operationalized selection criteria and the procedure was performed in a standardized manner. Subjects completed the Brief Pain Inventory (BPI) and the Hospital Anxiety and Depression Scale (HADS) just prior to the procedure and at one-month follow up. Scores on the HADS classified the subjects into three groups based on psychiatric symptoms, which formed the primary predictor variable: Low psychopathology group (n = 37) reported a mean of 23% improvement in pain at one-month while the High psychopathology group (n = 29) reported a mean worsening of -5.8% in pain (p < .001). Forty five percent (45%) of the Low group had at least 30% improvement in pain versus 10% in the High group (p < .001). Using an analysis of covariance, no baseline demographic, social, or medical variables were significant predictors of pain improvement, nor did they mitigate the effect of psychopathology on the outcome.Eighty six (86) subjects completed the study. The Psychiatric comorbidity is associated with diminished pain relief after a MBB injection performed with steroid at one-month follow-up. These findings illustrate the importance of assessing comorbid psychopathology as part of a spine care evaluation. Facet injections are among the most commonly performed non-surgical procedures in the United States for axial low back or neck pain, representing a range of techniques and indications PublisheThere is little agreement on what factors predict a successful outcome from facet injections and much depends on how they are used: indication (diagnostic vs. therapeutic), method (intrarticular vs. MBB), or medications (anesthetic only vs. steroid) Low-voluAn initial controlled trial found little therapeutic efficacy at six weeks for facet injections with corticosteroid But moreThere is, however, great variability in the subjects' responses to MBBs Few predBecause symptoms and anatomic findings are poorly predictive of results, it is difficult for clinicians to appropriately select patients for MBB injections. Although MBBs would not be indicated for everyone with axial pain, overly stringent selection criteria for performing these injections would likely exclude many who might otherwise benefit from this treatment. Yet, subgroups of responders in pain treatment studies of clinic populations can be identified reliably utilizing prospective observational designs based on possible predictive factors and applying operational inclusion criteria This sugPsychiatric illness–most often marked by depression, anxiety, and personality pathology–has been shown to be a significant predictor of treatment outcome for chronic musculoskeletal pain, regardleIn sum, psychiatric comorbidity is a negative predictor of treatment outcome in general for chronic musculoskeletal pain and the relationship between facet injection results and psychiatric illness is still unclear. The aim of this study was to evaluate whether psychiatric comorbidity predicted the outcomes of MBBs for patients with axial back or neck pain. We hypothesized that patients with high levels of depression and anxiety symptoms would have a diminished response to a therapeutic MBB compared with those with little psychiatric comorbidity.This was a prospective, observational cohort study done in a single, large, urban, university-based pain management center. After IRB approval from Brigham and Women's Hospital, all patients undergoing lumbar or cervical MBB injections were invited to participate. Data collection consisted of questionnaire surveys and de-identified medical records review. Seven physicians, all of whom were board-certified in Pain Medicine and had practiced together for at least 5 years, participated in this study.After giving verbal consent, subjects were considered for inclusion based on a decision by the treating physician to perform an MBB either as an independent therapy or as a prerequisite for a possible RFL. Patients were selected for an MBB based on the physician's assessment, which included: 1) obtaining a history of primarily chronic axial neck or low back pain, with radiation of pain in a common pattern for facet syndrome,,32 2) doAt the time of the initial evaluation a comprehensive treatment plan was proposed, which may have included the use of injections as well as multidisciplinary treatments of medications, physical therapy, and behavioral medicine, if indicated. The MBB procedure was performed at three or four levels in the cervical or lumbar spine, using local anesthetic at each level (1–2 mls of 0.5% lidocaine for skin and subcutaneous infiltration) and without any sedation. A 22 gauge spinal needle was then placed at each spinal level using flourscopic guidance, so that each needle was positioned at the junction of the transverse process and the superior articular process for lumbar injections and at the waist of the articular pillar for cervical injections. The injections consisted of methylprednisolone  and 0.25% bupivacaine (.5 ml) at each level, a total of 1.0–1.25 mls injectate volume per level. Depending on the physician's assessment of the patient's condition, injections were done unilaterally or bilaterally at 3–4 spinal levels. In all cases a total of 120 mg of methylprednisolone was injected.All measures were administered before the procedure and one-month afterwards. For patients who did not schedule a one-month follow-up visit, the scales were mailed after three weeks for them to complete and return. For those who missed their one-month visit, the scales were mailed to them that day.Percent improvement in average daily pain rating at one month was calculated using item 5  of the Brief Pain Inventory (BPI) The BPI High, Moderate, or Low levels of psychopathology) was the primary predictor. The treating physicians were blinded to group assignment. Group assignment was determined using the Hospital Anxiety and Depression Scale (HADS),[High, Moderate, or Low level of psychiatric comorbidity based on the subscale scores of the HADS. To be in the High group, scores had to be high on both the depression and anxiety subscales . To be in the Low group, scores had to be low on both subscales , and the Moderate group was all others not meeting High or Low criteria. This approach emphasizes the magnitude of difference in total negative affective symptoms between the Low and High groups and has been used in previous studies by the authors[The overall level of combined depression and anxiety symptoms (e (HADS), which ine (HADS), Using vae (HADS), Those wie authors,39Low and High groups. This is considered a clinically meaningful difference[We used a sample size calculation for a comparison of means of the primary outcome between the three groups. With Type I error of 5%, we sought 80% power to detect a 30% difference in pain improvement between the ifference Using daifference we assumHigh group would be less likely to be working or married, and more likely to be taking prescription opioids. We also included as covariates which physician performed the procedure and whether other treatments were begun at the time of the initial evaluation .An analysis of variance (ANOVA) was used to characterize the relationship between the primary predictor and outcome. Chi-square analysis was used to perform a responder's analysis of patients categorized as those with 1) at least 30% and 2) at least 20% improvement in pain. Twenty percent improvement was evaluated to examine whether the response trends were consistent between the groups at various levels of improvement. Baseline demographic, social, and pain history variables were included in an analysis of covariance (ANCOVA). The data used to calculate sample size requirements led us tOne hundred sixty six (N = 166) subjects were recruited and follow-up surveys were returned by 86 of 166 participants (52% response rate). No differences were found between the survey responders and nonresponders on any demographic, social, pain history, or psychiatric variables.High psychopathology, 20 of the subjects (23%) were in the Moderate psychopathology group, and 37 (43%) were in the Low psychopathology group. There was a significant correlation between levels of depression and anxiety . Of the survey responders, the High psychopathology group (n = 29) had a significantly lower percentage working (53%) and a significantly higher percentage (73%) taking prescription opioids (p < .05).The demographic, social, psychiatric, and pain history characteristics of those who had completed the 1-month follow-up surveys are presented in Table 2 = .17, p < .001), with the Low (23% improvement) vs. High (-5.8% worsening) groups having the most significant contrast between group comparison . None of the three groups reported significant improvements in the pain interference items of the BPI  at one month follow-up. Nor were there significant changes in anxiety or depression ratings after one month.Figure Low psychiatric morbidity group had a significantly greater percentage of patients with pain relief than either the Moderate or High groups. When the criterion was set at 20% improvement, the same trends were found.Figures F = 6.0, R2 = .18, p < 0.01), and no significant interaction was found.ANCOVA was used to test whether specific covariates altered the strength of the predictive relationship between psychopathology level and the degree of pain improvement from a MBB. First, separate univariate tests with percent pain improvement as the outcome were run for each of the baseline factors listed in Table High psychopathology group reported a 5% increase in pain from baseline, while the Low psychopathology group on average reported a 23% improvement in pain intensity. These differences are even more apparent in the responder analysis, in which the Low group had 2 to 4 times the rate of positive response (45–57%) than the High and Moderate groups (10–25%). Neither group showed significant improvements in function. The degree of improvement in the Low group was less than what has been reported in previous studies[This study examined the impact of psychiatric comorbidity on the response to medial branch blocks for spinal pain and demonstrated that patients with elevated levels of depression and anxiety are less likely to have a positive outcome after a MBB injection performed for axial low back or neck pain. One month following a MBB, the s studies We thinkLow and High psychopathology groups had clear contrasts in psychiatric symptoms, with levels in the High group consistent with major depression or generalized anxiety disorder diagnoses. Forty eight percent of the sample had either a high level of depression or anxiety. This is consistent with previous samples from pain clinics reporting a prevalence of psychiatric comorbidity ranging from 40–80%[The om 40–80%High group undermined any analgesic benefit of the MBB steroid injection.There is mounting evidence from neuroimaging studies that psychiatric overlay in chronic painful illnesses alters pain processing in the "pain matrix" in the brain,43 This These results suggest, however, that use of careful selection criteria may increase the likelihood that patients may benefit from steroid MBB injections for axial back or neck pain. Psychiatric assessment is an important component of any comprehensive spine care evaluation or treatment The admiFurthermore, psychiatric comorbidity is easily identifiable and inherently treatable in a medical setting, and the majority of psychiatric care in the United States is successfully delivered by primary care physicians utilizing medications and/or psychotherapy Even subWhile high levels of depression and anxiety were found to predict response to steroid MBB injections, just as interesting is that no other psychosocial  or medical variables  were found to have a significant impact on outcome. Recently, Cohen and colleagues reported that paraspinal tenderness predicted a positive response to RFL The resuThis study included a heterogeneous group of back pain patients, such as those with concurrent disc disease or spinal stenosis, and a MBB has been used by some as an aid to diagnose facet syndrome. Even though this study was not designed to confirm a diagnosis, the selection criteria for inclusion in the study made it less likely that these patients had radicular pain due to nerve root involvement or nonspecific low back or neck pain Given thLow group were placebo responses. But because the patients were treated with an MBB without the physicians knowing which group they were in, the nonspecific effects of treatment were minimized and the incidence of false-positive responses to the MBB procedure would likely be the same in our study groups.Another goal of a MBB, other than to clarifying a diagnosis, is to identify suitable patients for RFL. Commonly this is done by judging the short-term response to a MBB, using techniques such as the double-block method to reduce the incidence of false-positive responses. Since we were most interested in the one-month outcome after a therapeutic MBB with steroid in a group of uniformly selected patients, we did not utilize the double-block technique to determine candidacy for RFL, although this procedure might be considered in future studies. The design of this study did not offer the opportunity to evaluate the potential outcome from RFL after a steroid MBB, although future studies would be useful in determining whether treatment of psychiatric comorbidity prior to or in conjunction with doing an MBB would improve the response rate to an RFL. Furthermore, we cannot determine whether the positive results in the Several additional limitations of this study merit discussion: First, we were able to follow-up only 52% of the participants, and consequently, although not statistically significant, selection bias may have influenced the results. Next, unlike some previous studies, we did not focus on whether response to a MBB was useful in diagnosing facet-mediated pain. Rather, in a subtle yet salient departure, we concentrated on whether psychiatric factors predicted response to a therapeutic MBB with corticosteroid performed in patients with axial neck or low back pain. This is an equally relevant clinical issue, and as stated, this is a common indication for a MBB. We may have obtained different results had we designed the study as a diagnostic-based study rather than a treatment-based study. And lastly, we only collected 1-month follow-up data. It is possible that more frequent ratings over a longer period of time could have given different results.Despite these shortcomings, the results of this study suggest that high levels of psychopathology have a negative impact on MBB outcome. Importantly, no other medical or psychosocial covariates affected this result. Future studies should examine whether these findings extend to those undergoing RFL. It will also be fruitful to examine whether appropriate treatment of anxiety and depression in a group of patients with chronic pain improves the results of MBB injections and other procedural therapies.The authors declare that they have no competing interests.ADW was responsible for study design, data collection and analysis, and manuscript preparation. RNJ was responsible for study design and analysis and manuscript editing. LP was responsible for data collection. NP was responsible for data collection. SSN was responsible for data collection and manuscript editing. JNK was responsible for study design and analysis and manuscript editing. All authors read and approved the final manuscript.The pre-publication history for this paper can be accessed here: