Chronic neck pain is a major public health problem with very few evidence-based complementary treatment options. This study aimed to test the efficacy of 12 weeks of a partner-delivered home-based cupping massage, compared to the same period of progressive muscle relaxation in patients with chronic non-specific neck pain. Patients were randomly assigned to self-directed cupping massage or progressive muscle relaxation. They were trained and asked to undertake the assigned treatment twice weekly for 12 weeks. Primary outcome measure was the current neck pain intensity  after 12 weeks. Secondary outcome measures included pain on motion, affective pain perception, functional disability, psychological distress, wellbeing, health-related quality of life, pressure pain thresholds and adverse events. Sixty one patients  were randomized to cupping massage (n = 30) or progressive muscle relaxation (n = 31). After treatment, both groups showed significantly less pain compared to baseline however without significant group differences. Significant effects in favor of cupping massage were only found for wellbeing and pressure pain thresholds. In conclusion, cupping massage is no more effective than progressive muscle relaxation in reducing chronic non-specific neck pain. Both therapies can be easily used at home and can reduce pain to a minimal clinically relevant extent. Cupping massage may however be better than PMR in improving well-being and decreasing pressure pain sensitivity but more studies with larger samples and longer follow-up periods are needed to confirm these results.NCT01500330ClinicalTrials.gov  Chronic musculoskeletal pain syndromes, such as back and neck pain, are a major public health problem in all industrialized countries, with one in two people experiencing neck pain during their lives Most treatment options for chronic neck pain have proven only moderately effective to date Treatment guidelines also emphasize that patients should be encouraged to use therapies they can easily apply themselves; as long as they perceive them as effective. This might include the application of therapeutic heat  The trial exclusion criteria included neck pain caused by trauma, disc protrusion, whiplash, congenital deformity of the spine, spinal stenosis, neoplasm, inflammatory rheumatic disease, or active oncologic disease, affective disorder, addiction and psychosis. In addition, patients who were pregnant or who had had invasive treatment of the spine within the previous four weeks, or spinal surgery within the previous year were excluded. Finally, patients using opiates and long-term corticosteroid medication , those who had started a new treatment for neck pain within the previous six weeks, or were planning to start such treatment within the following twelve weeks were also excluded.Patients were randomly assigned to one treatment group using a non-stratified block-randomization approach with randomly varying block lengths. The “ranuni” random number generator of the SAS/STAT ® software  was used to generate random numbers. Sequentially numbered sealed envelopes containing patients’ treatment assignments were prepared by a statistician who was not involved in conducting the study. Following each baseline assessment, the trial coordinator opened the next lowest numbered envelope to reveal patient’s treatment assignment. During the active treatment phase, only the trial coordinator had contact with patients and knew of their group allocation. The trial coordinator was not involved in patients’ outcome assessments and the outcome assessor remained blind to patients’ group allocation throughout.These participants, and a partner, relative or friend, as appropriate, attended a one-hour practical workshop to learn how to use cupping massage. The clinic regularly runs such sessions to teach patients and their partners cupping massage methods for home use. The workshop was led by an experienced teacher and two assistants and it began with an overview of the history, indications and contraindications of cupping massage, followed by its technique, risks and possible side effects. Cupping massage was then demonstrated by the teacher and a patient volunteer. Patients, and those accompanying them, then practiced the cupping massage technique, with staff members providing feedback and suggestions for improvement as needed. Patients practiced until they felt competent to use the cupping massage technique unaided. All patients were given a cupping glass , 200 ml of arnica massage oil  and detailed written information to take home. Patients were advised that they could attend a further ‘refresher’ session, at any time during the trial, if they felt that they needed to. They were asked to contact the trial coordinator if they wished to attend such a session, but none did so. Patients were also asked to contact the trial coordinator if they experienced any adverse events. All patients were telephoned halfway through the study to promote compliance with the trial and its treatments. All patients further received an instruction sheet in German with a summary of treatment advices, see appendix 1.Two treatment sessions per week of 10–15 minutes’ duration each at comfortable intensity were recommended. Patients were advised that cupping massage might cause petechiae and ecchymosis for several days; necessitating awareness in social settings such as swimming pools.Progressive muscle relaxation is a systematic technique used to achieve a deep state of relaxation, developed by Edmund Jacobson Patients were asked to practice relaxation at home twice a week for 20 minutes a session and to record their practice in a diary. At the end of the trial, they were also offered a cupping massage workshop, a cupping glass  and 200 ml of arnica massage oil , as incentives to complete the study.The primary outcome measure was perceived pain, as recorded on a 100 mm Visual Analogue Scale (VAS) To measure pain on motion, patients were asked to flex, extend, laterally flex and laterally rotate their necks to the left and right. The evoked pain was measured on a 100 mm VAS, for each direction. An average pain on motion score was then calculated from these data for each patient Patients’ affective perception of pain was measured using the Pain Description List (SBL), a 12-item short form of the Pain Perception Scale (SES) Patients’ functional neck-related disability was measured using the Neck Disability Index (NDI) Patients’ psychological distress was measured using the 14-item Hospital Anxiety and Depression Scale (HADS) Health-related quality of life was assessed using the Short Form 36 Health Survey Questionnaire (SF-36) The results of additional measures of stress perception  2 probe. Pressure was applied, using this instrument, in increments of 40 kPa/s until patients indicated a perception of pain in addition to pressure. PPTs were determined where patients perceived maximal pain. They were also measured bilaterally at three anatomically predefined sites; over the levator scapulae muscle , the descending part of the trapezius muscle (midway between C7 and the acromion process) and the semispinalis capitis muscle  Patients’ pressure pain thresholds (PPT) were measured using a digital algometer  with a 1 cmAll patients used a log to record the daily intensity of their pain (VAS), their medication, cupping massage or relaxation practices and any other concurrent treatments. To analyze patients’ medication usage, compliance and concurrent treatments the number of days where patients used pain medication, cupping or progressive muscle relaxation and physiotherapy was calculated for each week. Patients also noted weekly whether they obtained adequate relief from their neck pain, on a ‘yes/no’ basis  All patients rated their expectations that cupping massage and progressive muscle relaxation would be successful on a 100 mm VAS with 0 mm indicating not successful at all and 100 mm indicating highest possible expectation. For analyses only the expectation towards the assigned treatment was used.All adverse events were recorded. Patients experiencing such events were asked to see the study physician to assess their import and initiate any necessary response.A previous study of cupping massage for chronic non-specific neck pain After study start the study statistician was no longer available for analysis, therefore analysis had been conducted by the study coordinator. Final analysis plan and all analyses were conducted on an ‘intention-to-treat’ basis, including all patients who were randomized, regardless of whether they gave a full set of data or adhered fully to the study protocol. Missing data were completed with the value of the last available record (last observation carried forward), instead of using the Markov chain Monte Carlo multiple imputation method, as initially planned.2 test for categorical data. Outcome data were analyzed using univariate analyses of covariance (ANCOVA) which modeled each post-treatment outcome as a function of treatment group (classified factor), patients’ expectations (linear covariate), and its respective baseline value (linear covariate).Baseline data comparability was ensured using Student’s t-tests for continuous data and xPatients’ compliance with their allocated treatment regimes, pain levels, medication usage and concurrent treatments (daily logs) were analyzed using repeated measures ANCOVA with patients’ expectations as a linear covariate . In case of significant interaction, exploratory post-hoc tests were applied without Bonferroni correction for multiple testing. All analyses were done using SPSS software , instead of SAS/STAT®-Software , as initially planned.The Consort flowchart of patient recruitment is shown in the Patients ranged in age from 24 to 74 years . Most weThe pattern of patients’ compliance for the 12 weeks of the trial can be seen in The pattern of patients’ use of concurrent treatments for the 12 weeks of the trial can be seen in  = 9.43, p<0.001). In week 12, no significant group difference was found between the CM and the PMR groups regarding pain intensity on the VAS as the primary outcome measure  rather than the single treatment Potential modes of action of the cupping massage may involve increased local microcirculation; thought to reverse hypersensitivity. Hypersensitivity is seen mainly as a consequence of peripheral sensitization Limitations of this study include different patients’ expectations of treatment effectiveness, which were entered as a covariate into the analyses, controlling for the influence of this variable.A further limitation comes from patients’ high withdrawal rate prior to randomization that may have resulted in an underpowered study. Given the observed effects even the original sample size would not have been enough to detect differences in pain intensity. Furthermore, since most of the patients withdrew before randomization, the risk of a biased sample might also be very small.Limitations may also arise from unknown differences between the partner-administered cupping massage treatment and relaxation exercises delivered solely by CD. A lack of a long-term follow-up and the impossibility of blinding patients and workshop providers to patients’ treatment allocations, are also possible sources of bias.The study’s strengths include the adaptation of existing trial designs to investigate cupping massage and muscle relaxation in a non-clinical setting; providing results that are easily applied to everyday life. Its other strength is its use of a randomized controlled design with blinded outcome assessors, which is, however, only relevant for physiological outcome measures. The inclusion of an active control group practicing a relaxation method recommended by German neck pain guidelines In conclusion, cupping massage is no more effective than progressive muscle in reducing chronic non-specific neck pain. Both therapies can be easily used at home and can reduce pain to a minimal clinically relevant extent. Cupping massage may however be better than PMR in improving well-being and decreasing pressure pain sensitivity but more studies with larger samples and longer follow-up periods are needed to confirm these results.Protocol S1Trial protocol. Original study protocol in German as submitted to the ethics committee of the University Hospital Essen .(DOCX)Click here for additional data file.Protocol S2Trial protocol. English translation of the study protocol submitted to the ethics committee of the University Hospital Essen.(DOCX)Click here for additional data file.Checklist S1CONSORT Checklist.(DOC)Click here for additional data file.


Shoulder pain is reported to be highly prevalent and tends to be recurrent or persistent despite medical treatment. The pathophysiological mechanisms of shoulder pain are poorly understood. Furthermore, there is little evidence supporting the effectiveness of current treatment protocols. Although myofascial trigger points (MTrPs) are rarely mentioned in relation to shoulder pain, they may present an alternative underlying mechanism, which would provide new treatment targets through MTrP inactivation. While previous research has demonstrated that trained physiotherapists can reliably identify MTrPs in patients with shoulder pain, the percentage of patients who actually have MTrPs remains unclear. The aim of this observational study was to assess the prevalence of muscles with MTrPs and the association between MTrPs and the severity of pain and functioning in patients with chronic non-traumatic unilateral shoulder pain.An observational study was conducted. Subjects were recruited from patients participating in a controlled trial studying the effectiveness of physical therapy on patients with unilateral non-traumatic shoulder pain. Sociodemographic and patient-reported symptom scores, including the Disabilities of the Arm, Shoulder, and Hand (DASH) Questionnaire, and Visual Analogue Scales for Pain were compared with other studies. To test for differences in age, gender distribution, and education level between the current study population and the populations from Dutch shoulder studies, the one sample T-test was used. One observer examined all subjects (n = 72) for the presence of MTrPs. Frequency distributions, means, medians, standard deviations, and 95% confidence intervals were calculated for descriptive purposes. The Spearman's rank-order correlation (ρ) was used to test for association between variables.MTrPs were identified in all subjects. The median number of muscles with MTrPs per subject was 6 (active MTrPs) and 4 (latent MTrPs). Active MTrPs were most prevalent in the infraspinatus (77%) and the upper trapezius muscles (58%), whereas latent MTrPs were most prevalent in the teres major (49%) and anterior deltoid muscles (38%). The number of muscles with active MTrPs was only moderately correlated with the DASH score.The prevalence of muscles containing active and latent MTrPs in a sample of patients with chronic non-traumatic shoulder pain was high. Shoulder pain, which is often persistent or recurrent, is one of the major reasons patients consult with primary healthcare providers -6. HowevMyofascial trigger points (MTrPs) may offer an alternative explanation for the pathophysiological mechanisms underlying shoulder pain. In recent years, our understanding of the etiology, pathophysiology, and management of MTrPs has increased -30. MTrPMTrPs are classified into active and latent myofascial trigger points. Active MTrPs are characterized by the presence of clinical pain and constant tenderness. Specifically, active MTrPs prevent full lengthening and weakening of the muscle. Diagnostically, active MTrPs refer patient-recognized pain upon compression and mediate a local twitch response in muscle fibers when stimulated. When compressed within the patients' level of pain tolerance, active MTrPs produce referred motor phenomena and often sympathetic hyperactivity, , and cause tenderness in the pain reference zone. In contrast, latent MTrPs are clinically quiescent, and are only painful when palpated. With the exception of spontaneous pain, a latent MTrP can present with all the clinical characteristics of active MTrPs. In addition, latent MTrPs are within a taut band that increases muscle tension and restricts patients' range of motion . AlthougIn clinical practice, identification of MTrPs is usually performed by palpation. In a recent study , we confThe aim of this study was to determine the prevalence of MTrPs and the correlation between MTrPs and pain and functioning, in a sample of patients presenting with chronic, non-traumatic unilateral shoulder complaints.This observational study was embedded in a clinical trial  addressing a specific treatment of patients with shoulder pain . The ComStudy participants were recruited from patients participating in a controlled trial investigating the effectiveness of physical therapy on patients with unilateral, non-traumatic shoulder pain. This study was conducted at a primary care practice for physical therapy, which specializes in the treatment of patients with disorders of the shoulder, the neck, and upper extremities. A power analysis was performed prior to beginning this study, and it was calculated that 104 subjects were needed for the clinical trial.All patients who contacted the practice for non-specific shoulder complaints from September 2007 until September 2009 were requested to participate in the study. The inclusion criteria were 1) age between 18 and 66 years; 2) unilateral non-traumatic shoulder pain; and 3) duration of symptoms of more than six months. Patients were excluded from the study if they presented with a prior diagnosis of shoulder instability, shoulder fractures, any systemic diseases, or a medical history or examination suggestive for the presence of neurological disease, internal diseases, or psychiatric disorders. All patients signed a written informed consent before participating in the study.To determine the potential general applicability of this study to primary care shoulder pain patients, we searched for Dutch studies conducted on primary care patients from 1995 until 2009. Eight studies were found and sociodemographic data  were analyzed and compared to the current study population -55.At baseline, age, gender, hand dominance, and education level were recorded. For comparison reasons we classified the education level as high education , medium education , and low education  . ShouldeFor every study participant, one of the two available observers measured the passive range of motion (PROM) of the shoulder in flexion, internal and external rotation, abduction, and  adduction with a handheld digital inclinometer . Range of motion was expressed in degrees and presented as the sum of the value measured for the non-affected shoulder minus the value measured for the affected shoulder. A positive value means that the affected shoulder had impaired range of motion as compared to the non-affected shoulder.Next, the observer examined each subject for the presence of MTrPs in the shoulder muscles of their affected shoulder according to the guidelines outlined in Simons et al ; the nonhttp://www.dash.iwh.on.ca/) [The DASH-DLV is a widely used multidimensional  30-item self-reporting questionnaire that focuses on physical function, pain and other symptoms. DASH-DLV scores ranges from 0 to 100, with higher scores indicating greater disability. DASH is a reliable and valid questionnaire, with good to excellent intra- and inter-rater reliability, and good correlation with the Shoulder Pain and Disability Index. Because of these advantages, DASH is considered to be one of the best questionnaires available for shoulder symptoms (.on.ca/) ,60.The VAS-P is a self-report scale consisting of a 100 mm horizontal line anchored by word descriptions on each side . VAS-P cData was collected and transferred to a worksheet by a research assistant .W test was used to test for normality of the data. Because the number of muscles with MTrPs  was not normally distributed we used the Spearman's rank-order correlation (ρ) test for all variables. For interpretation of the ρ-values, we used the classification proposed by Feinstein [Frequency distributions, means, medians, standard deviations, and 95% confidence intervals were calculated for descriptive purposes. The Shapiro-Wilk einstein . A correp  < 0.05) and the proportion of female subjects was higher (p  < 0.05) compared to these other studies. In addition, the current study population was more highly educated (p  < 0.05) than the previous study populations for which educational data was reported [A flowchart describing patient participation is depicted in Figure reported ,5,52. CoW = 0.95; p < 0.05; W = 0.96; p <0.05 respectively).Muscles containing active MTrPs were found in all 72 subjects. The median number of muscles with active MTrPs per subject was 6 (range 2 to 16). Muscles containing latent MTrPs were found in 67 subjects. The median number of muscles with latent MTrPs per subject was 4 (range 0 to 11). Figure Active MTrPs were found in the infraspinatus muscle in 56 subjects and in the upper trapezius muscle in 42 subjects. In addition, active MTrPs were highly prevalent in the middle trapezius (n = 31), anterior deltoid (n = 34), middle deltoid (n = 36), posterior deltoid (32), and teres minor (n = 34) muscles.Latent MTrPs were found in the infraspinatus muscle in 11 subjects and in the upper trapezius in 27 subjects. Latent MTrPs were found in the teres major muscle in 35 subjects and in the anterior deltoid muscle in 27 subjects. Figure W = 0.97; p <0.05 and W = 0.91; p < 0.05 respectively). VAS-P1, VAS-P2, and VAS-P3 scores were also considered to be normally distributed, although the Shapiro-Wilk test did present borderline results for VAS-P2 and VAS-P3.The mean score on the DASH was 30.8 . Mean VAS-P scores were follows: the VAS-P score for 'current pain' (VAS-P1) was 30 , for 'average pain in the last seven days' (VAS-P2) was 42.1  and for 'for the most severe pain in the last seven days' (VAS-P3) was 56.6 . The mean PROM score, calculated as the sum the PROM value measured for the non-affected shoulder minus the PROM value measured for the affected shoulder, was 32.4 degrees , where a positive value indicates that the affected shoulder has a impaired range of motion. Both DASH and PROM scores were normally distributed (p <0.05) and VAS-P1 scores , and poorly correlated with VAS-P2  and the duration of the shoulder pain . We were unable to detect statistically significant correlations between the number of muscles with MTrPs (either active or latent) and VAS-P3  or the PROM  scores. Table The number of muscles with active MTrPs only moderately correlated with the DASH-DLV  were reported for active MTrPs compared to latent and patients with shoulder pain displayed lower PPT than healthy subjects . Second,To date, unilateral shoulder pain has mainly been proposed to be due to either the presence of inflammation in the subacromial tendons and bursae, or degenerative rotator cuff ruptures . Although these pathological structures may cause pain, it is also known that similar abnormalities have been found in asymptomatic shoulders.Active MTrPs, which are painful spots that produce familiar shoulder pain during contraction, stretching or compressing, these MTrPs may provide an alternative explanation for shoulder pain, which is independent of the presence of subacromial abnormalities. According to Simons, Travell and Simons , MTrPs wBased on the results of this study, we propose that an alternative approach may be indicated for the assessment and management of patients with chronic, non-traumatic shoulder pain. Current treatment regimens consist primarily of pharmacological interventions, including anti-inflammatory medications, or muscle strengthening exercises. If MTrPs are one of the main reasons for shoulder pain (active MTrPs) and altered motor activation patterns (active and latent MTrPs), as several authors have proposed, then anti-inflammatory treatment ,48,70 anIf the above hypothesis is true, treatment of MTrPs could provide an innovative, promising therapy for shoulder pain. This study shows the results of patients' characteristics for a sample of patients with chronic, unilateral non-traumatic shoulder pain, who were recruited for a randomized clinical trial to study the results of MTrPs directed interventions by physical therapists in this group. The results of this study are published.We compared sociodemographic data from the current study population with similar data from several other Dutch shoulder pain research studies. Because none of these studies investigated MTrPs, we made this comparison to see whether there was reason to expect that the high prevalence of MTrPs we observed was unique to our population. In our study population more females were included, and the subjects were significantly younger and more highly educated than subjects from the other Dutch populations, although a specific explanation for these differences is lacking. There is no reason to suspect that educational levels correlate with the number of MTrPs and awareness of educational levels is mainly important for effectiveness studies, because they may impact the patients' motivation and compliance ,73. HoweOne of the limitations of our study is that we only examined patients with unilateral chronic shoulder pain and dysfunction, whereas MTrPs are thought to be responsible for both acute and chronic pain. It is conceivable that patients who developed chronic shoulder pain may have more MTrPs, and persistent MTrPs in the acute phase than patients who recover easily. In future research projects assessment of MTrPs in patients with acute shoulder problems should also be included. The small sample size is another limitation of this study. Before starting this study a power analysis was performed and it was calculated that 104 subjects would be needed for the clinical trial. After two years (one year more than originally planned, 72 subjects were enrolled in the study. For practical reasons, the study was completed with this smaller sample size, which may have influenced some of the results of this study. We used two observers in this study with identical clinical experience and post-graduate training on myofascial trigger point therapy. In addition, both observers found a comparable mean number of active MTrPs. Because there was no statistically significant difference in mean DASH scores obtained by the two observers, we consider both groups to be comparable and the findings obtained by both observers to be similar.This study demonstrates that MTrPs are very prevalent in patients with chronic unilateral, non-traumatic shoulder pain. In addition, the number of MTrPs is only moderately correlated with DASH-DLV outcome measures and VAS-P pain measures, indicating that MTrPs contribute to the clinical picture of common shoulder pain problems. We recommend that the MTrP examination and treatment should be considered for patients with shoulder pain in both future clinical studies and clinical practice.All authors have read, edited and approved the final manuscript. CB is the lead investigator, and developed the design of the study, carried out data-acquisition, analysis, interpretations, and prepared the manuscript as primary author. MW and RO provided advice on the study and the manuscript, and supervised the study. JD and BS provided intellectual contributions to the manuscript.The authors declare that they have no competing interests.The pre-publication history for this paper can be accessed here:http://www.biomedcentral.com/1471-2474/12/139/prepub


COMT) and opioid receptor μ-1 (OPRM1) common functional polymorphisms rs4680 and rs1799971 were associated with the incidence, intensity, or duration of CPP in patients after lower abdominal surgery.Preoperative pain, type of operation and anesthesia, severity of acute postoperative pain, and psychosocial factors have been identified as risk factors for chronic postsurgical pain (CPP). Recently, it has been suggested that genetic factors also contribute to CPP. In this study, we aimed to determine whether the catechol-O-methyl transferase (One hundred and two patients with American Society of Anesthesiologists (ASA) physical status I/II underwent either abdominal radical prostatectomy (n = 45) or hysterectomy (n = 57). The incidences of CPP in the pelvic and scar areas were evaluated in all patients three months after surgery.COMT rs4680, 22 (21.6%) patients had Met158Met, 55 (53.9%) patients had Val158Met, and 25 (24.5%) patients had Val158Val. No association was found between CPP phenotypes  and different rs4680 genotypes. For OPRM1 rs1799971, only CPP patients carrying at least one copy of the G allele had higher pain intensity than A118A carriers (p=0.02). No associations with other phenotypes were found. No combined effect of COMT/OPRM1 polymorphisms on CPP phenotypes was observed.Thirty-five (34.3%) patients experienced CPP after lower abdominal surgery. Within this group, six (17.1%) patients demonstrated symptoms of neuropathic pain. For OPRM1 genotype influences CPP following lower abdominal surgery. COMT didn’t affect CPP, suggesting its potential modality-specific effects on human pain. GCH1) ), age, and gender. No significant associations were identified assuming the dominant or recessive genetic model of variant or minor allele of the two SNPs , dominant (P = 0.27), and recessive (P = 0.57) genetic models of the variant or minor allele . No statistical difference was found in duration of pain among CPP patients with different genotypes of rs1799971 (Table In the CPP group (35 patients), our analyses of rs4680 did not identify any significant association with the intensity of pain after adjusting for baseline acute pain, age, and gender, assessing the additive  /A118A (21.6%), Met158Val (GA) /A118A (43.1%), Met158Met (AA)/A118A (17.6%), and Met158Val (GA) /A118G (8.8%) (Table COMT/OPRM1 genotypes.We identified four common (frequency > 5%) combined ) /A118A 3.1%, MetChronic postsurgical pain is a prevalent, though often overlooked healthcare problem. Twenty-five percent of patients attending pain clinics reported surgery as the cause of chronic pain, with an estimated CPP incidence of 10-65% ,14. The COMT gene are associated with altered sensitivity to pain induced in an experimental (controlled) environment. Low COMT activity poses a high risk for the development of chronic orafacial pain and fibromyalgia [COMT enzyme encoded by the 158Met allele  may result in accumulation of epinephrine and norepinephrine in the peripheral and CNS, leading to overstimulation of nociceptive beta 2/3-adrenergic pathways and high pain sensitivity as observed in 118G carriers [COMT inhibition causes increased pain sensitivity comparable to the pro-nociceptive effects of carrageenan mediated by beta 2/3-adrenergic mechanisms [COMT functional variation to clinical outcome after surgical treatment for disk degenerative disease [COMT rs4680 Val/Val homozygous group compared to the Met/Met homozygous group [COMT rs4680 and the incidence, intensity, or duration of CPP. These findings suggest the modality-specific nature of COMT effects, e.g. it contributes to acute postoperative pain after lower abdominal surgery, but not persistently or chronically. These data are important, since COMT’s effects on human pain are still under investigation, and more evidence is needed for a complete picture. That COMT is not associated with several pain conditions such as neuropathic pain syndromes already points to possible modality-specific effects [COMT genotyping may potentially have value for clinical decision-making based on predicted pain severity or time course or patients’ response to analgesia [COMT’s effects in different pain models and for multiple pain phenotypes to identify precisely the array of clinical settings in which COMT could be used as a “pain biomarker”. Although our results provide additional knowledge on the relationship between COMT and CPP, they are limited to only one time point (three months postoperatively) and should be confirmed in a larger clinical setting using protocols specifically designed to investigate the intensity, quality, and duration of pain in scar regions at different time points after surgery.Nonetheless, not all patients experience pain around the scar area after surgery. Genetics, as well as interaction between genetic and environmental factors, are likely to influence inter-individual variability in CPP ,9. Namelomyalgia . Decreascarriers . Furtherchanisms . Recentl disease . We alsous group . In this effects ; this stnalgesia , it is eOPRM1 A118G genotype (rs1799971) have been well characterized [OPRM1 SNP and the incidence of CPP; however, the intensity of reported pain was significantly higher in carriers of the G allele compared to the homozygous AA carriers. Interestingly, these data match results from several studies in other patient populations where the G allele was found to be associated with elevated mechanical pain responses, [OPRM1 G allele is a risk factor for chronic postsurgical pain and elucidate OPRM1’s effects on other human pain models.Functional genetic polymorphisms between altered pain thresholds and analgesic responses to opioid administration for the cterized . In the sponses,  as well sponses, ,28. A laCOMT/OPRM1 genotypes and the incidence of chronic postsurgical pain in our study population, the CPP patients with Met158Met/A118G had higher pain scores than those patients with Val158Val/A118A, Met158Val/A118A, and Met158Met/A118A. However, as the sample size was too small to perform any powerful analyses, the results need to be interpreted very cautiously and more studies with larger sample sizes are needed to validate this finding.Although no significant association was found between combined COMT and OPRM1 variation [It is important to acknowledge a few limitations in our study. Both genes tested have complex genetic structures, and the two SNPs tested do not cover the diversity of ariation . AlthougCOMT/OPRM1 polymorphisms in this patient population. Nevertheless, this data further improves our understanding of the genetic background of different types of CPP, and of the complexity of the effects of COMT and OPRM1 polymorphisms on human pain.No statistically significant association was found between the incidence of CPP after lower abdominal surgery and This study was approved by the local Human Studies Committee in Tallinn, Estonia . After providing informed consent, 102 Caucasian patients with ASA physical status I/II (57 women and 45 men) underwent abdominal surgery . BaseliA standardized, general anesthesia technique was used for all patients . For indPostoperative analgesia: After arrival at the PACU, patients were asked every 30 minutes whether they needed analgesics until they were alert enough to use the patient-controlled analgesia (PCA) pump [CA) pump . When anThe incidence of the postoperative residual pain in the pelvis and at the scar area was evaluated in all 102 patients three months after surgery , by a rOPRM1 exon 1 (from the genomic sequence accession number NC000006 nucleotides 154402000–2800) was amplified by PCR with primers F1: CAGAAGAGTGCCCAGTGAAGA and R755: TACCTCCCCTCTTTCATCCTC and sequenced directly with the additional primer F177: CGCAGAGGAGAATGTCAGATG. COMT exon 4  was amplified by PCR with primers F206: CTCATCACCATCGAGATCAAC and R301: CCTTTTTCCAGGTCTGACAAC. Amplified DNA was cut with the restriction enzyme Hin1 II. When Guanosine was added after gel agarose (2%) electrophoresis, 87 and 29 base pair long fragments were created. Adenosine gave rise to 69, 18, and 29 base pair long fragments. The genotyping error rate was directly determined by re-genotyping 25% of the samples randomly chosen for each locus. The overall error rate was determined to be < 0.005.Whole blood samples were transported to the Department of Gene Technology at the Tallinn University of Technology, where genotyping analysis was performed . LymphocNumerical variables were summarized using the mean and standard deviation, and categorical variables were summarized as N and percentage (%). Patients’ demographics and baseline characteristics between CPP and non-CPP patients were compared using t-test or Fisher’s exact test.OPRM1 and COMT SNPs. First, multiple logistic regression analysis was used to test all patients for association between CPP status and each SNP, adjusting for age, sex, and baseline pain score. We evaluated additive, dominant, and recessive genetic inheritance  models for each SNP in relationship to CPP status, in which the genotypes were coded as , , and  based on the numbers of variant alleles. In other words, the homozygote of the wide-type or major allele was always used as the referent category for statistical comparison. Second, for the CPP patients, the association of each SNP with the intensity of CPP score (or duration of pain) was evaluated assuming three gene-dosage effect models after adjusting for sex, age, baseline pain score, and pain medication using the analysis of covariance (ANCOVA) method. Similar analyses were also performed for combined COMT/OPRM1 genotypes.Before genetic association analysis, Hardy–Weinberg equilibrium (HWE) was first assessed via exact test and confirmed for the P-value of less than 0.05 was considered to be statistically significant.All statistical analyses were performed using the SAS software, version 9.2  and the PLINK software . A P-valCPP: Chronic postsurgical pain; SNP: Single nucleotide polymorphism; COMT: Catechol-O-methyl transferase; OPRM1: Opioid receptor μ-1; CNS: Central nervous system; PACU: Post-anesthesia care unit; NRS: Numeric rating score; ASA: American society of anesthesiologists.We declare no conflict of the interests.YK - Protocol design, protocol submission and management, data analysis, manuscript preparation. BG - Study conduction, data collection, manuscript drafting and review. AL - Study conduction, data collection, manuscript drafting and review. AV– Genetic study conduction, data collection, manuscript drafting and review. LQ – Data interpretation, manuscript review. FD – Statistical analysis, data interpretation, manuscript review. IB - Statistical analysis, data interpretation, manuscript review, editing and submission. All authors read and approved the final manuscript.Pain scores and duration of pain in 35 CPP patients stratified by gender.Click here for fileCOMT rs4680 and OPRM1 rs1799971.Distribution of genotypes by gender for Click here for file


Central sensitization has recently been documented in patients with knee osteoarthritis (OAk). So far, the presence of central sensitization has not been considered as a confounding factor in studies assessing the pain inhibitory effect of tens on osteoarthritis of the knee. The purpose of this study is to explore the pain inhibitory effect of burst tens in OAk patients and to explore the prognostic value of central sensitization on the pain inhibitory effect of tens in OAk patients.Patients with knee pain due to OAk will be recruited through advertisements in local media. Temporal summation, before and after a heterotopic noxious conditioning stimulation, will be measured. In addition, pain on a numeric rating score, WOMAC subscores for pain and function and global perceived effect will be assessed. Patients will be randomly allocated to one of two treatment groups . Follow-up measurements will be scheduled after a period of 6 and 12 weeks.Tens influences pain through the electrical stimulation of low-threshold A-beta cutaneous fibers. The responsiveness of central pain-signaling neurons of centrally sensitized OAk patients may be augmented to the input of these electrical stimuli. This would encompass an adverse therapy effect of tens. To increase treatment effectiveness it might be interesting to identify a subgroup of symptomatic OAk patients, i.e., non-sensitized patients, who are likely to benefit from burst tens.NCT01390285ClinicalTrials.gov:  Osteoarthritis (OA) is characterized by damaged articular cartilage of synovial joints. About 17% of people aged over 45 years suffer from pain and loss of function due to symptomatic knee osteoarthritis (OAk) ,3. The pTranscutaneous electrical nerve stimulation (tens) is a non-pharmacological, inexpensive and safe form of analgesia . The paiCentral sensitization is defined as "an augmentation of responsiveness of central pain-signaling neurons to input from low-threshold mechanoreceptors" . CentralThe effectiveness of tens on knee pain in OAk patients is unclear, due to conflicting results . The ambIn case of central sensitization, the response to peripheral stimuli, e.g., electrical stimuli as well as mechanical pressure, cold, heat, light, sound and chemical substances is enhanced . Tens , Brussels, Belgium. The research protocol is approved by the Medical Ethics Committee of the university hospital of the Vrije Universiteit Brussel (UZ Brussel). Written and signed informed consent will be obtained from all participants.A community sample of OAk patients with knee pain will be recruited.To be included, patients need to be over 50 years old. All should have osteoarthritis in at least one knee fulfilling the American College of Rheumatology classification criteria  and repoPatients are excluded if they have had a knee surgery or intra-articular corticosteroid or hyaluronic acid injection  within 6Patients will be recruited through advertisements placed in local media. All patients will initially be screened over the phone with regard to selection criteria. If appropriate they will undergo medical screening with a project rheumatologist.Consequently, an appointment for the baseline measurements will be made. Due to ethical considerations, analgesia and non-steroidal anti-inflammatory drugs will be permitted (and registered) as required and as participants are used taking during the last month. All participants will be asked to refrain from seeking other forms of treatment during the trial. They will be questioned about having received other forms of treatment in the final stage of the protocol.Following baseline measurements, subjects will be randomly allocated to one of two treatment groups, ie., tens or sham tens. However, all patients will be told that two different kinds of tens are being tested. Randomization will be performed in blocks of four, stratified by sex and age. The allocation of this will be done by an independent researcher who will not interfere with other experimental procedures. We will use two boxes: one for each sex. In each box, subgroups will be made for five age categories: 50-59; 60-69; 70-79; 80-89; 90-99 years. Four numbered cards will be put in each age category. The numbering of the cards starts at one and ends at 40 and each number will correspond to a tens or a sham tens treatment. At the start of the study, each age category contains two tens and two sham tens treatments. Each time a new patient is included, a card will be taken out of the corresponding box and age category. When the four cards of one category are used, all of them will be put back in the box, so that a second round can be started. At each round, the numbered cards will be differently assigned to a tens/sham tens treatment by an independent researcher. The measurements will be carried out by a different researcher than the one that informs the patients concerning the treatment modalities. The information of the baseline measurements will remain concealed until the end of the study ensuring blinded assessment.Sample size calculation is based on data from Law and Cheing . They foAge, gender, BMI, duration of knee OA symptoms, medication use, previous treatment and surgery for knee OA will be obtained at baseline.Overall average knee pain (KPa) and peak pain intensity over the last 24 h (KPp) will be assessed by a 11-point numeric rating scale with terminal descriptors of 0 = no pain; 10 = maximal pain . Self-reTemporal summation as well as diffuse noxious inhibitory control will be used to detect central sensitization. The assessment will be done in accordance with the protocol of Cathcart et al. . The outPressure stimuli will be measured using a hand held digital algometer . Pain detection thresholds will be measured on the knee  and on the upper part of the homolateral arm  . The preTemporal summation assessment will start 2 min after PPT measurements to avoid contamination by possible sensitization from the pain threshold stimulation. TS will be induced at the knee and arm through 10 pressure pulses with the hand held algometer  at PPT intensity. For each pulse, pressure will be increased at a rate of 2 kg/s and held during 1 s. An interstimulus interval of 1 s will be applied. Patients will be instructed to rate their pain level according to a NRS at the first, 5th and 10th pulse .Ischemic compression of the heterolateral arm will be used as heterotopic noxious conditioning stimulation to evoke diffuse noxious inhibition control (DNIC). This method has previously been described ,21. A toThe subjects that enter the tens -group will be asked to apply the tens therapy for at least 40 minutes continuously per day during 6 weeks. All patients in the intervention group will be informed that the intensity should be high enough so that an unpleasant but non-painfull sensation is acquired. The settings of the current will not change during the study. The patients that are assigned to the sham tens treatment will receive an inactive placebo tens therapy using a nonfunctional unit that appears to work but provides no stimulus. To blind the investigator as well as the patient, the sham tens device will deliver current for 30 seconds and then ramps down to no current. This approach has been studied and has been proven effective in blinding subjects and investigators to eliminate expectation bias . All parThe settings of the current: burst tens with pulse width of 250 μsec; internal frequency: 100 Hz; burst frequency 3 Hz; intensity: until an unpleasant but non-painful sensation is acquired. The tens devices  to be used will be pre-set with the current settings. Subjects will be taught how to switch on and off the device and how to augment the intensity (mA) of the burst tens current. Patients will be asked not to change the current settings. The electrodes will be placed in the dermatome L4 at 10 cm above the knee. Potential adverse effects may be irritation of the skin near the electrodes."overall average knee pain" (KPa) and "peak pain over the last 24 h" (KPp) will be measured using a numeric rating scale [The change from baseline to final assessment of the study knee in the continuous variables ng scale .self-reported knee pain and difficulty with physical function will be measured using the WOMAC Index [The change from baseline to final assessment of the study knee in AC Index .global perceived effect (GPE) compared to baseline will be measured on an ordinal scale  [The  better) . The GPE better) -38.medication use will be recorded as another pain variable.The change from baseline to final assessment of Pressure pain threshold, temporal summation (TS) and Diffuse noxious inhibition control (DNIC) will be used as baseline variables.During the 6 weeks following the first appointment, a study nurse will contact the participants of the tens and stens groups weekly by telephone. Subjects will be asked about any inconvenience with the handling of the tens device as well as if they have received other treatments.Pressure pain threshold, temporal summation (TS) and Diffuse noxious inhibition control (DNIC) will be assessed as well.After 6 and 12 weeks participants will be asked to rate their GPE, as well as KPa, KPp, WOMAC and medication use. At these occasions An intention-to-treat analysis will be performed so that the integrity of the randomization is ensured. Normality will be checked via the Shapiro-Wilk test.To ensure good balance of participant characteristics in each group at baseline, stratification is used . ChangesAs a secondary analysis, a linear regression analysis will be used with the following dependent factors: BMI, TS and DNIC; and as independent factors: KPa, KPp, WOMAC subscales for pain and function.Significance value for all tests will be set at p < 0.05. All analyses will be performed using SPSS 20 for Windows.This study has a double aim. First, to explore the pain inhibitory effect of tens in OAk patients. Second, to assess whether components of central sensitization like temporal summation and diffuse noxious inhibitory control, affect this pain inhibitory effect.It is believed that tens influences pain through different pathways. One of these pathways is the gate-control theory . The secAs tens may influence pain through the electrical stimulation of low-threshold A-beta cutaneous fibers, the responsiveness of central pain-signaling neurons of OAk patients who are centrally sensitized is augmented to the input of these electrical stimuli. This would encompass an adverse therapy effect of tens on the pain perception in patients with OAk who are centrally sensitized. Therefore we think that it might be interesting to identify a subgroup of symptomatic OAk patients, i.e., non-sensitized patients, who are likely to benefit from burst tens.The majority of studies that were published in the past and that focused on treatment effects of tens, embody currents that were administered by a therapist in a practice or hospital setting. As portable tens devices are marketed as small, inexpensive, easy-to-use home units , we chooTo assess whether dose-effects may influence the treatment outcome, we plan to record the daily duration of the electro stimulation that is applied.One major concern when using self-administered medical care is treatment adherence. We think that a weekly phone call after the initial start of the study may improve treatment adherence as well as stimulate participants to consistently fill out the diary.We have chosen a daily treatment duration of 40 minutes continuously. This is based on the findings of Cheing and colleagues . They foThe results of this study will not only provide insight into the effect of tens but they may contribute to future studies investigating the identification of patient subgroups that may benefit from tens.BMI: Body Mass Index; DNIC: Diffuse Noxious Inhibitory Control; GPE: Global Perceived Effect; KPa: overall average knee pain intensity; KPp: peak knee pain intensity; NRS: Numeric Rating Scale; OA: Osteoarthritis; Oak: Osteoarthritis of the knee; PPT: Pressure Pain Threshold; Tens: Transcutaneous Electrical Nerve Stimulation; TS:Temporal Summation; Stens: sham Transcutaneous Electrical Nerve Stimulation; WOMAC: Western Ontario and McMaster Universities; OI: Osteoarthritis Index; WDR: Wide Dynamic Range.The authors declare that they have no competing interests.DB drafted the manuscript.WDH has been involved in drafting the manuscript, revised it critically for important intellectual content and made substantial contributions to conception and design of the manuscript.PL revised the manuscript critically for important intellectual content.IB made substantial contributions to conception and design of the manuscript and revised it critically for important intellectual content.PV has been involved in drafting the manuscript and revised it critically for important intellectual content.All authors have given final approval of the version published.


After surgery, effective and well-directed acute pain therapy is a necessary and integral part of the overall treatment plan. Generally, the assessment of pain intensity depends on a patient’s self-evaluation using scoring systems such as numeric rating scales . Recently, a “Pain Monitor” was commercially provided which is based on measurements of fluctuations of skin conductance (NFSC). In this randomized, controlled, single-blind trial, possible benefits of this certain device were studied.Postoperative patients (n = 44) were randomly assigned to a test or a control group during their stay in the postanesthesia care unit (PACU). All patients were treated and monitored according to internal hospital standards. Whereas all patients systematically evaluated their pain each 15 min, test group patients were additionally addressed when NFSC exceeded a predefined level. In cases of NRS≥5 during a routine elevation or in between, pain relief was achieved by standard procedures irrespective of group allocation.During their stay in PACU, both test and control groups experienced a significant decrease in NRS as a consequence of pain therapy. No significant differences in mean NRS or in NFSC values were found between the test and control groups. No correlation was observed between NRS and NFSC.Postoperative patients experience diverse stressors, such as anxiety, disorientation, shivering, sickness and pain. Although the application of continuous pain monitoring would be meaningful in this clinical setting, the tested device failed to distinguish pain from other stressors in postoperative adult patients.DRKS00000755.German Clinical Trials Register  Despite standard interventions, postoperative pain remains a major inconvenience for approximately 50% of patients As long ago as 1967, the measurement of skin electrical properties was found to be a promising method to quantify hypnosis. Nisbet et al. stated that changes in skin conductance (SC) were already mentioned in 1888 The aim of our study was to evaluate the possible benefits of continuously monitoring pain intensity for postoperative patients by measuring NFSC with a commercially provided device. The primary outcome parameter of this randomized, controlled, single-blind trial was the mean pain intensity of postoperative patients during their stay in PACU as measured by NRS.This randomized, controlled, single-blind trial took place in PACU at the University Hospital Aachen after approval by the local ethics committee (EK 063/11) and registration at the German Clinical Trials Register (DRKS00000755). From April, 28th to June, 10th, 2011, 44 patients were informed preoperatively about the study via a standardized leaflet and provided written consent for their participation. The protocol for this trial and supporting CONSORT checklist are available as supporting information; see After admission to PACU, a standardized data sheet titled “beginning of treatment” was used. In this form, vital data, initial NRS (0–10) and NFSC score, modified Aldrete score  In cases of pronounced pain (NRS≥5) detected during a routine evaluation or in between, pain relief was achieved by standard procedures regardless of group allocation. Generally, in addition to a non-opioid analgesic 0.05 to 0.1 mg per kg body weight of piritramide was administered and titrated to effect. These events were recorded on an additional sheet titled “pain aggravation” to document vital data, NRS score, NFSC value and the antinociceptive effect after 5 min.When NFSC reached the predefined threshold of 0.27/s for at least 30 s, which corresponds to NRS≥4 or “other stressors” as detailed in the Med-Storm Pain Monitor manual, patients in the TC group were asked whether there was an initiating pain, which was treated when identified . These ePrior to discharge from PACU, a final data acquisition titled “end of treatment” was performed in a manner similar to the first evaluation .The primary endpoint was defined as the mean NRS score expressed by the patient during the whole stay in PACU. Secondary endpoints were the ratings of subjective conditions , the duration of stay in PACU, total dose of administered analgesics and mean Aldrete score.The number of required subjects was determined by a prior power analysis using nQuery Advisor 7 : A priori, two-tailed t test, power 0.8, α = 0.05. The hypothesis was an expected reduction of NRS mean value by 20% and a standard deviation of ±25% in each group.SPSS Statistics 19 for Windows  was used for statistical analysis. Apart from Kolmogorov-Smirnov test and Spearman’s correlation, Mann-Whitney-U-Test was used for independent data samples (TC versus CO group) and Wilcoxon Test for repetitive parameter assessments . Mean plus/minus standard deviation is given for all normally distributed parameters, otherwise median and interquartile range is stated. MedCalc  was applied for ROC analysis that was performed in addition to provided endpoints.In total, 55 patients were screened as possible subjects by studying the surgery schedule for the next day. After arrival at the PACU, 44 of them were evenly allocated to the CO and TC group .After group allocation, the study groups showed similar characteristics with respect to sex  vs. 16 females (CO)), age (54.6±14.4 (TC) vs. 59.1±14.4 (CO)), number of total intravenous anesthesia (8 cases each) and vital data .During the stay in PACU, no significant differences were observed between TC and CO groups in either primary or secondary endpoints. Furthermore, the hypothesized difference of 20% concerning the primary endpoint was not achieved. In particular, mean NRS score was 2.8 (IQR 1.4–4.2) and 3.1  respectively- a relative difference of 9.6%. Additionally, NFSC did not differ at any time. After discharge from PACU, NRS scores differed significantly between TC and CO groups .As expected, pain intensity decreased significantly during the stay in PACU in both TC (5 (IQR 2–6) vs. 3 (IQR 2–4), p<0.05) and CO group (4 (IQR 2–5) vs. 2 (IQR 0–2), p<0.01) showing no inter-group differences. Concerning subjective condition scores, vigilance differed in the CO group (p = 0.04) and well-being differed in the TC group (p = 0.02) between arrival at PACU and discharge. Administered analgesics were similar in both groups. Total number of severe pain episodes requiring piritramide administration was 33 in CO versus 35 in TC group (p = 0.75). Total dose of piritramide was higher by tendency in TC group .No correlations were observed between NRS and NFSC. Manually derived NFSC and mean NFSC values (time period of 60 s) correlated according to Pearson’s method . Regarding ROC analysis, best sensitivity (77.9%) and specificity (41.2%) were obtained for the detection of NRS>2 with the criterion NFSC>0.13/min .In this randomized controlled trial, we examined whether the measurement of NFSC is an effective method to improve acute pain therapy in postoperative patients. As our primary endpoint, mean NRS scores during patients’ recovery phase was observed and compared. No differences between the TC and CO groups were observed for this parameter or any secondary endpoints. In particular, the hypothesized decrease of 20% regarding the mean NRS score in TC group was not achieved.While NFSC did not differ between the time points within the groups, the NRS score was significantly higher in the TC group at the end of PACU care. In both groups, pain intensity decreased significantly during the stay in PACU to a tolerable value of lower than three as expected. All patients had already received analgesics ) under anesthesia according to clinical standards . TherefoConcerning subjective condition scores between arrival at PACU and discharge, vigilance increased significantly (p = 0.04) in the CO group and well-being increased in the TC group (p = 0.02). However, assessing all “subjective conditions” items was especially challenging for sleepy or somnolent patients. For sleeping patients, scores were rated by the observations of the medical attendant.post-hoc compared with mean NFSC values over time frames of 15 s, 30 s and 60 s (NFSC60). The strongest correlation found was between manual NFSC and calculated NFSC60.Although the software used for online NFSC calculation was clearly arranged, user friendly and NFSC values were refreshed each second, these values fluctuated frequently and were therefore difficult to determine. To overcome this difficulty, the attendant was instructed to observe the NFSC for at least 30 s to identify and document the predominant value. This approach was intricate and error-prone. Hence, manually derived values were Nevertheless, no significant correlation was observed between NRS and NFSC. Consequently, the sensitivity and specificity for pain detection obtained via ROC analysis were weak. Thus, the area under the curve (AUC) is barely better than 0.5 which correspond to flipping a coin.There are several possible explanations for these findings. Changes in NFSC were already caused by addressing the patient to assess pain intensity or subjective sensations. Although NFSC was documented prior to questioning, this fact implies a strong interaction of skin conductance (or its measurement) with other factors. Even artifacts such as moving the arm or the hand to which the electrodes were attached led to errors in measurement. Moreover, not only pain but also stress in general  affects patients after surgery. Unfortunately, these factors are manifold and almost unpredictable.Recently, various clinical trials of the ability of SC measurement to detect stress came to different conclusions In 1981, Wallin described a correlation between neurophysiological reactions and variations in electrodermal activity Several intraoperative trials have indicated that palmar SC reaches a high sensitivity and specificity (up to 86% each) in the detection of noxious and awakening stimuli relative to hemodynamic parameters and BIS In contrast to these results, trials that took place in PACU show a more heterogeneous pattern. Similar to our results, NFSC failed to reflect acute postoperative pain in a trial from Ledowski et al. in 2009 Several limitations of this study must be addressed. Whereas we used few inclusion criteria, a more homogeneous study population with regard to psychiatric diseases, chronic pain and more similar surgeries could reveal more subtle differences between study groups. Patients in the CO and TC group were interrogated every 15 min and were treated with analgesics if their pain score was moderate. Certainly, on the one hand this design makes a differentiation difficult but on the other hand, this is a very common procedure in PACU that we did not want to downgrade for the study. Besides, we didn’t use cognitive tests or questionnaires. Concerning this matter, we didn’t expect relevant differences and didn’t want to influence normal PACU processes too deeply. Patients were blinded according to the assigned group; the medical attendant who documented the data periodically was not. However, in the CO group, the NFSC value was only scored every 15 min (but not in between) for documentation, thereby minimizing any impact on the attendant’s behavior.An objective technique to assess the pain intensity of communication-hindered patients remains a promising but elusive goal. Although the application of continuous pain monitoring would be meaningful especially in postoperative patients, the tested device failed to distinguish pain from other stressors.Protocol S1Original study protocol prepared for clinical trial translated from German.(DOCX)Click here for additional data file.Checklist S1Checklist filled out according to CONSORT criteria.(DOC)Click here for additional data file.


Chest pain is a common reason for referral to pediatric cardiologists. Although pediatric chest pain is rarely attributable to serious cardiac pathology, extensive and costly evaluation is often performed. We have implemented a standardized approach to pediatric chest pain in our pediatric cardiology clinics as part of a broader quality improvement initiative termed Standardized Clinical Assessment and Management Plans (SCAMPs). In this study, we evaluate the impact of a SCAMP for chest pain on practice variation and resource utilization.P<0.001). The number of exercise stress tests obtained was significantly lower in the SCAMP-enrolled patients compared with the historic cohort . Similarly, there was a 66% decrease in utilization of Holter monitors and 75% decrease in the use of long-term event monitors after implementation of the chest pain SCAMP . The number of echocardiograms obtained was similar between groups.We compared demographic variables, clinical characteristics, and cardiac testing in a historical cohort (n=406) of patients presenting to our outpatient division for initial evaluation of chest pain in the most recent pre-SCAMP calendar year (2009) to patients enrolled in the chest pain SCAMP (n=364). Demographic variables including age at presentation, sex, and clinical characteristics were similar between groups. Adherence to the SCAMP algorithm for echocardiography was 84%. Practice variation decreased significantly after implementation of the SCAMP (Implementation of a SCAMP for evaluation of pediatric chest pain has lead to a decrease in practice variation and resource utilization.  Therefore, we created a standardized approach to pediatric chest pain that has been implemented across our department as part of a broader quality improvement initiative, which we have termed Standardized Clinical Assessment and Management Plans (SCAMPs).The outpatient management of chest pain in children is often resource intensive and costly despite the exceedingly low incidence of cardiac pathology.10 On the basis of periodic review of the collected data, the SCAMP algorithm is designed to be modified. The goals of the SCAMPs initiative, including the chest pain SCAMP, are to improve patient care, decrease practice variation, and reduce unnecessary resource utilization and cost.SCAMPs is a novel quality improvement methodology that standardizes the assessment and management of a relatively diverse patient population with a single presenting symptom or condition and incorporates a systematic yet selective data collection process.11 Our objective of this study was to evaluate the effect of the chest pain SCAMP on practice variation and resource utilization.Our previous analyses have predicted that utilization of several diagnostic tests including echocardiograms, exercise stress tests (ESTs), and outpatient rhythm monitors could be substantially reduced using the chest pain SCAMP leading to an ∼20% reduction in costs without negatively affecting patient care.11 This algorithm is targeted at identifying cardiac causes of chest pain. Testing recommendations were based on a recent report from Kane et al.6 Over a 10-year period, there were 32 cases of serious underlying cardiac pathology presenting with chest pain to our outpatient cardiology department. By retrospective review, all of these cardiac diagnoses could have been identified by using history, physical examination, ECG, or echocardiography alone, without the use of other diagnostic tests such as EST or outpatient rhythm monitors.As detailed in prior work from this institution, we developed an algorithm that forms the basis of the chest pain SCAMP using history, physical examination, and ECG to suggest when further diagnostic testing including an echocardiogram, EST, or outpatient rhythm monitor is indicated.11 Patients in the historic cohort were similarly excluded if they had a known history of heart disease or if they had a prior evaluation for chest pain by a pediatric cardiologist. The Institutional Review Board for Clinical Research at Children's Hospital Boston approved the use of patient medical records for the retrospective review.All patients between 7 and 21 years of age presenting to our outpatient pediatric cardiology clinic for a first-time evaluation of chest pain were enrolled in the chest pain SCAMP. Patients enrolled in the SCAMP from June 1, 2010, through May 31, 2011, were included in this analysis. Children with a known history of heart disease were excluded. We previously reported on a similar cohort of patients  who presented for initial evaluation of chest pain in 2009 (the most recent pre-SCAMP year), identified by International Classification of Diseases, Ninth Revision (ICD-9) billing codes for chest pain.We collected demographic and clinical characteristics for each patient including historical features of the chest pain and associated symptoms, past medical history, family history, physical examination findings, and electrocardiographic results. For SCAMP-enrolled patients, these data were collected on SCAMP data forms completed by the provider at the time of the visit. For patients in the historic cohort, the same data were retrospectively ascertained from the cardiologist's clinic note created at the time of the visit.To target potential cardiac causes of chest pain, pertinent positive clinical history included whether the pain was associated with exertion or exertional syncope, radiated to the back, jaw, left arm, or left shoulder, increased with supine position, or was temporally associated with fever. Past medical history was considered positive if the patient had a condition that could lead to an increased risk of pathologic chest pain including systemic arthritis/vasculitis, a hypercoaguable state, or prolonged immobilization. Family history was considered positive if any of the following were present in a first-degree relative: sudden or unexplained death, cardiomyopathy, or a hypercoaguable state. Pertinent positives on physical examination included a pathological murmur, gallop, pericardial friction rub, abnormal second heart sound, distant heart sounds, peripheral edema, painful or swollen extremities, tachypnea, or fever .Electrocardigraphic interpretation was based on documented findings in the cardiologist's clinic note in the historical cohort and on the SCAMP data form for the SCAMP cohort. Ventricular hypertrophy, pathological ST-segment or T-wave changes (>2 mm), high-grade atrioventricular block, ventricular or atrial ectopy, low QRS voltages, PR segment depression, S1/Q3/inverted T3, or a prolonged QTc>470 ms were considered positive criteria.Echocardiography, EST, and Holter and long-term event monitor results were obtained from reports generated at the time of the study in the historical cohort and from the SCAMP data form in the SCAMP group. Testing was generally obtained at the time of or soon after the initial visit for chest pain. Diagnoses from these tests that were considered potential cardiac causes of chest pain included specific coronary anomalies, cardiomyopathy, myocarditis, pericarditis, pulmonary hypertension, aortic dissection, and pulmonary embolism.We analyzed adherence to the SCAMP algorithm in terms of echocardiography. We examined how often providers ordered an echocardiogram when indicated by the SCAMP as well as how often they followed recommendations not to order an echocardiogram when it was not indicated by the SCAMP. Practice variation for diagnostic testing was also determined . Variation was assessed at the patient level. Patients were seen by 34 providers in the historic cohort  and 36 providers in the SCAMP cohort  during the study period. The number of cardiac tests obtained in conjunction with the clinic visit was analyzed. All patients in both cohorts had at least 1 cardiology clinic visit. An ECG was performed at all clinic visits. Resource utilization for echocardiograms, ESTs, Holter monitors, and event monitors was compared between the 2 groups.Explanations for deviations from the SCAMP were collected from data provided at the time of the visit either in the SCAMP data form or in the clinic note. For echocardiograms that were not recommended by the SCAMP but were still ordered, reasons for deviation were categorized into the following: parental concern, underlying medical illness , abnormal physical examination finding (unlikely to be related to chest pain), or other.Demographic and clinical characteristics were compared between groups using Fisher's exact or the Wilcoxon rank sum test as appropriate. Resource utilization was compared between groups using Fisher's exact test.P value for this test statistic.We assessed practice variation in the use of echocardiography, EST, Holter, and event monitoring at the encounter level between the 2 time periods as follows. There were 16 possible testing combinations using these 4 tests . In the Explanations for SCAMP deviations were expressed as counts and percentages. All statistical analysis were 2-sided and type I error was controlled at a level of 0.05. Analyses were performed with SPSS  and S-Plus .P-enrolled patients  of cases. When an echocardiogram was not indicated by the SCAMP, providers followed the recommendation not to obtain an echocardiogram 83.8%  of the time.P<0.001)  underwent no testing in addition to ECG, while the majority of the remaining patients underwent echocardiogram only (19%), EST only (9%), or the combination of the two (16%). In the SCAMPs cohort, only 8 testing patterns were observed; the majority of patients underwent no additional testing (53%) or echocardiogram only (39%). This represented a statistically significant reduction in practice variation in the SCAMP cohort compared with the historic cohort (P<0.001) .P=0.001). Holter monitor  and long-term event monitor  utilization was also lower in the SCAMP cohort. There was no difference in echocardiography utilization between the 2 groups  (P=0.001) , the number of patients who did not have an echocardiogram was lower in the SCAMP group compared with the historic cohort  . AdditioP=0.001) .Provider explanations for deviations from the chest pain SCAMP with regard to echocardiograms are shown in Importantly, no abnormalities were detected on cardiac evaluation that represented a cardiac etiology for chest pain. There were, however, several incidental diagnoses discovered by echocardiography including 2 patients with a bicuspid aortic valve and 1 patient with a large secundum atrial septal defect. Two children were also found to have a high origin of the right coronary artery near the sinotubular junction. The take-off in 1 of these patients was from a somewhat leftward aspect of the right sinus of Valsalva with an origin that was somewhat acutely angled, although considered unlikely to be the cause of this child's single episode of chest pain.Chest pain is a common problem in pediatrics and a frequent reason for referral to a pediatric cardiologist. In contrast to adult populations, chest pain in childhood is rarely related to cardiac pathology. Despite this distinction, the diagnostic approach to pediatric chest pain varies considerably among clinicians without any clear consensus. In this study, we demonstrate a reduction in practice variation and resource utilization using a SCAMP for the evaluation of pediatric chest pain.12 SCAMPs represent a potential unique algorithm-based solution in which understanding and controlling variation can lead to consistent behavior where outcomes can be measured and practice can be systematically improved based on analysis of sound deviations.Practice variation contributes to inefficiency and cost in healthcare delivery. This variation has been well documented in the management of a broad range of disease processes over the past few decades. In Medicare patients, for instance, adjusted per capita spending in the year 2000 was more than double in Manhattan, NY, than in Portland, OR. Importantly, however, high-intensity practice patterns amongst Medicare patients (in part characterized by the number of diagnostic tests performed) were associated with lower quality care and worse adjusted outcomes than more conservative practice patterns.10 Pediatric chest pain is particularly suited for this type of analysis given the wide variation in clinical decision making, lack of evidence-based guidelines based on rigorous analytic study, the low incidence of true cardiac pathology, as well as the extensive resource utilization and cost related to its management.SCAMPs were developed as part of a broader quality improvement initiative to reduce practice variation in clinical decision making, but unlike clinical practice guidelines or other protocol-driven algorithms, SCAMPs have several unique features that distinguish them from these previously established methodologies. The inception of SCAMPs is in part related to a lack of evidence-based guidelines and difficulty in conducting large-scale, prospective, randomized clinical trials within our specialty which often form the basis of algorithms such as clinical practice guidelines. Unlike other quality improvement tools, SCAMPs are applied to conditions where there is no “best” practice but only “sound” practice based on existing data in combination with expert clinical consensus. The SCAMPs process is iterative with rigorous data collection and timely revision of guidelines based on these data. Accordingly, SCAMPs are primarily focused on the content of guidelines as opposed to the process of executing evidence-based guidelines. The SCAMPs process allows for and in fact encourages deviations in care plan based on knowledge-based preferences with the only requirement that deviations are explained in order to improve the care algorithm.9 Incidental diagnoses, however, are not uncommonly found by diagnostic cardiac tests such as echocardiography or outpatient rhythm monitoring.9In this study, we focused on a SCAMP applied to pediatric patients presenting specifically to our outpatient cardiology clinic with chest pain. Several studies have attempted to characterize this patient population, though to our knowledge this is the first study to implement a SCAMP-type process. In general, other authors have also found that echocardiograms and other diagnostic tests are obtained in a significant number of children presenting with chest pain with low yield in identifying a cardiac etiology.13 In the SCAMP period, utilization of this test decreased to just over 3% of patients. Significant reductions were also seen in the utilization of outpatient rhythm monitoring devices including Holter and event monitors.Provider adherence to the chest pain SCAMP for echocardiography was approximately 84% and this contributed to a significant decrease in practice variation. As noted above, given the iterative nature of the SCAMP algorithm, perfect adherence is not the goal. Resource utilization significantly decreased for a number of diagnostic testing modalities commonly used in the evaluation of chest pain. Most notably, in the year prior to the implementation of the chest pain SCAMP, nearly 30% of patients presenting to our outpatient cardiology department with chest pain underwent exercise stress testing despite a lack of established clinical utility demonstrated in several studies.Translating reductions in resource utilization into actual cost savings is challenging and requires several assumptions. However, using a blended cost/charge ratio of 60% and assuming that an equivalent number of patients had presented to our clinic after SCAMP implementation, our reductions in diagnostic testing could have lead to potential cost savings of over $160 000 during this time period. As national concerns surrounding healthcare financing continue, novel methods of decreasing healthcare spending while delivering high-quality patient care will be increasingly essential.11 A number of factors may account for the continued higher use of echocardiography. First, the vast majority of echocardiograms were obtained based on historical features of the chest pain, particularly if the pain was exertional in nature. The initial chest pain SCAMP did not specifically define “exertional chest pain” and thus resulted in variable interpretation of this characteristic.Despite the SCAMP algorithm, the utilization of echocardiography did not change significantly though there appeared to be a trend toward more appropriate utilization of echocardiography with regards to its use in exertional and nonexertional chest pain. In our prior analysis, when the chest pain SCAMP was theoretically applied to the historical cohort of patients, we predicted an approximately 20% decrease in echocardiogram utilization.Additionally, providers cited a variety of reasons for ordering echocardiograms not indicated by the SCAMP. For instance, several providers obtained echocardiograms to alleviate parental anxiety. In several other patients, coexisting medical conditions  or physical examination findings felt to be unrelated to chest pain  were noted as reasons for obtaining an echocardiogram. Even with substantial reduction of some studies such as exercise stress testing and outpatient arrhythmia monitoring, echocardiography remains a heavily used resource with no yield of a cardiac etiology for chest pain during the SCAMP study period. Further modifications of the SCAMP may potentially lead to a reduction of echocardiogram utilization in the future.14 This can occur while awaiting test results or as a result of identifying anatomic variants or anomalies unrelated to chest pain that have no known clinical impact . Despite reassurance and appropriate counseling, these diagnoses can be anxiety provoking and lead to potential behavior modification of a child's activities or participation in athletics. Additionally, some families may have been reassured by the fact that the provider was following a set of expert consensus guidelines used by our entire department. In this regard, the SCAMP may facilitate a discussion as to why a particular patient may not warrant additional testing.In addition to the financial benefits achieved in reducing unnecessary testing, this SCAMP may have a positive psychosocial effect by decreasing patient and parental anxiety that is generated in part by additional testing.1 Moreover, as noted previously, the 37 patients with a potential cardiac etiology for chest pain would have all been identified using the chest pain SCAMP.6 Furthermore, we cannot account for additional resource utilization for patients seeking further evaluation after an initial visit in our outpatient clinic, an area that will be the focus of future investigation. The ability to generalize the effect of the chest pain SCAMP to other settings may be limited as our population is prescreened and referred for a higher suspicion of a cardiac etiology for chest pain. Lastly, patients with significant cardiac pathology may be incompletely captured if the referred chief complaint is different from chest pain and chest pain is elicited secondarily. Despite these limitations, this preliminary study demonstrates that the SCAMPs process can streamline provider practice patterns and reduce variation in diagnostic testing.Despite our findings, this study has several limitations. Data collection was accomplished using retrospective review in the historical cohort whereas we used a form completed by the physician at the time of encounter in SCAMP patients. This difference may account for the increased frequency of associated complaints such as palpitations reported in the SCAMP cohort and may overestimate our perceived improvement in more appropriate echocardiography usage. Second, although we only identified a few cardiac causes of chest pain in our historical group (pericarditis), no cardiac etiology for chest pain was identified in the current SCAMP group. It is possible that we have missed pathology, which may present in alternative settings such as an emergency department or with longer-term follow-up. Notably however, a recent report from our institution found that of 3700 pediatric patients presenting with chest pain, there were no deaths attributable to cardiac pathology over a median follow-up of 4.4 years.In this study, we report a significant decrease in practice variation and resource utilization after implementation of a novel quality improvement methodology for pediatric chest pain. The use of echocardiography remains largely unchanged despite predicted decrease. Future iterations of the chest pain SCAMP can potentially refine data collection and recommendations to reduce echocardiogram use without increasing missed diagnoses.