Minimal interventional procedures are frequently applied in patients with mechanical low back pain which is defined as pain presumably resulting from single sources: facet, disc, sacroiliac joint or a combination of these. Usually, these minimal interventional procedures are an integral part of a multidisciplinary pain programme. A recent systematic review issued by the Dutch Health Insurance Council showed that the effectiveness of these procedures for the total group of patients with chronic low back pain is yet unclear and cost-effectiveness unknown. The aim of the study is to evaluate whether a multidisciplinary pain programme with minimal interventional procedures is cost-effective compared to the multidisciplinary pain programme alone for patients with chronic mechanical low back pain who did not respond to conservative primary care and were referred to a pain clinic.All patients with chronic low back pain who are referred to one of the 13 participating pain clinics will be asked to participate in an observational study. Patients with a suspected diagnosis of facet, disc or sacroiliac joint problems will receive a diagnostic block to confirm this diagnosis. If confirmed, they will be asked to participate in a Randomized Controlled Trial (RCT). For each single source a separate RCT will be conducted. Patients with a combination of facet, disc or sacroiliac joint problems will be invited for participation in a RCT as well. An economic evaluation from a societal perspective will be performed alongside these four RCTs. Patients will complete questionnaires at baseline, 3 and 6 weeks, 3, 6, 9 and 12 months after start of the treatment. Costs will be collected using self-completed cost questionnaires.No trials are yet available which have evaluated the cost-effectiveness of minimal interventional procedures in patients with chronic mechanical low back pain, which emphasizes the importance of this study.National Trial Register: NTR3531 Non-specific low back pain is a widespread problem with major social and economical consequences ,2. Non-sIn lower back pain, 80 – 90% is of mechanical origin . MechaniThe aim of this project will be to provide a valid, reliable and precise answer to the question whether minimal interventional procedures supplementary to a multidisciplinary pain programme for patients with chronic mechanical low back pain who are referred to a pain clinic are more effective and cost-effective compared with the multidisciplinary pain programme alone.An observational study and four RCTs with a full economic evaluation will be performed. The observational data will inform about the proportion of patients with a positive or negative diagnostic test for facet pain, disc pain, SI-joint pain and a combination of these, and the clinical outcomes of patients with a negative diagnostic test. Patients diagnosed with facet, disc, SI-joint or combination pain, by means of a diagnostic block will be asked to take part of one of the four RCTs. The observational study will monitor patients who do not want to, or are not eligible to participate in the RCTs. Figure In June 2012, the study was approved by the Medical Ethics Committee of the Erasmus Medical Centre in Rotterdam (registration number MEC-2012-079) and the study protocol was registered at the Dutch Trial Register (number NTR3531). Written informed consent will be obtained before entering the study.In this study all patients aged between 18 and 70 years, referred to a pain clinic with suspected chronic mechanical low back pain and without improvement of symptoms after conservative treatment will be invited to participate in the observational study. Further inclusion criteria for the RCTs are: a) a 50% or more reduction in perceived pain at 30 minutes after a diagnostic block; or b) the provocative discography must be positive. According to the International Association for the Study of Pain (IASP) and the International Spinal Injection Society (ISIS), a provocative discography is positive when the familiar pain at the target level is provoked with a pain score of 7 out of 10, and two painless adjacent control discs are present .Exclusion criteria are pregnancy; inability to complete the questionnaires; anticoagulant drug therapy and/or coagulopathy; Body Mass Index higher than 35; involvement in a work related conflict; severe psychiatric or psychological problems. Patients will be asked to complete five questionnaires, three of which serve to indicate whether patients with psychiatric or psychological complaints need to be excluded. Distress, depression, anxiety, somatisation, pain acceptance and pain coping strategies will be assessed with the Four-Dimensional Symptoms Questionnaire (4DSQ) ,22, the Only the 4DSQ , CPAQ (z-score > 2 in pain willingness) and PCL (z-score > 2 in catastrophizing and limitations) will be used for exclusion from the RCTs. Patients will be excluded if they score above the predefined thresh-hold in any of the questionnaires.Patients are recruited in the pain-treatment clinics of the participating hospitals. General practitioners and medical specialists who referred patients to the pain clinics will be informed about participation of their patients in the study. The anaesthesiologists identify and inform potential participants from among their clinic’s patients. If a patient meets the eligibility criteria and agree to participate in the trial, the patient will be asked to sign an informed consent form.Anaesthesiologists at the participating clinics will conduct the diagnostic tests and the minimal interventional procedures. Every participating pain clinic has a referral agreement with three or four physiotherapy practices in their region. These will provide a standardized exercise programme. The psychological interventions, if necessary, will take place in a usual care setting.Each patient will receive the exercise programme and psychological help (if necessary). The patient in the intervention group will receive the Minimal Interventional Procedures as well. Together, this will form the multidisciplinary pain programme. The selection of eligible patients in the diagnostic phase by performing a test block, as well as the exercise programme (which we standardized for the study) and the minimal interventional procedures are usual care at Dutch pain clinics, as described in the current guideline anaesthesiological pain control ,29.All participants of the trials will receive a standardized exercise programme based on the guideline low back pain of the Royal Dutch Society for Physical Therapy . The proIf necessary, the anaesthesiologist or physiotherapist can refer the patient to the psychologist. The patients will receive usual care.Supplementary to the exercise programme, and possibly a psychological support, the intervention group will receive minimal interventional procedures. This will take place according to a pre-specified approach, based on the current guideline anaesthesiological pain control :1. Patients with facet joint pain will receive radiofrequency lesion of the first ramus dorsalis at Lumbar vertebrae (L)3, L4, L5 and S1.2. Patients with intervertebral disc pain will receive Intradiscal Electrothermal Therap (IDET) or Biacuplasty of the involved disc.3. Patients with SI- joint pain will receive the Cooled radiofrequency, radiofrequency lesion pallisade technique or Simplicity III probe technique of the ramus dorsalis at L4, L5, S1, S2 and S3.4. Patients with a combination of the single entities will be divided, after the clinical diagnosis, to a group who receives minimal interventional treatments .In both treatment groups, the patients are asked to refrain from any co-interventions during the intervention period. However, co-interventions after the initial intervention period will be monitored and evaluated. If patients in the non-interventional study group have not improved or recovered after three months, they will not receive interventional procedures but will return to the General Practitioner or medical specialist that had referred them to the pain clinic.The core set of primary outcomes recommended for low back pain research will be used . All webThe baseline questionnaire includes socio-demographic characteristics , the complaint history, all primary and secondary outcomes and patient expectation. Patient expectation will be assessed with the 10-point scale Credibility/Expectancy Questionnaire (CEQ) ,35.There are three primary outcomes: pain intensity, global perceived recovery and functional status.Pain intensity over the previous week will be measured on an 11-point Numerical Rating Scale (NRS) (0 = no pain to 10 = worst imaginable pain) . Among cGlobal perceived recovery will be measured by self-assessment on a 7-point NRS ranging from ‘completely recovered’ to ‘worse than ever’, as for example described by Kamper et al. . This inFunctional status will be measured according to the Dutch translation of the Oswestry Disability Index (ODI-NL) . This inHealth-related quality of life will be measured with the EuroQol (EQ-5D) . This quPatient satisfaction will be assessed using a written 7-point NRS ranging from ‘not satisfied at all’ to ‘completely satisfied’. No gold standard is available for the measurement of patient satisfaction, but in spinal disorders a seven-point global question is recommended .General health will be evaluated with the Rand-36 . This quChronic pain experiences is measured by the Multidimensional Pain Inventory (MPI) . The MPIThe use of care in the pain clinics will be registered by local research nurses. They will register the type, amount and results of the diagnostic tests and treatments  the patients receive. Costs of the multidisciplinary pain programme, other health care utilization, patient and family costs, and production losses will be included and relevant data collected using self-completed cost questionnaires . Work abAn overview of the data-collection is presented in Table Using a power of .9, alpha .05 and a correlation of .5 for repeated measurements, a total of 85 patients per group are needed to detect a clinically relevant mean difference of two points on the NRS for pain intensity (SD 4) . This diThrough an ‘educated guess’ a SD of four was chosen, because no SD can be found in the literature. Though arbitrary, it is believed conservative, and will ensure that enough patients will be included to find clinically relevant effects, if present.Patients who respond positively to the diagnostic test and give informed consent will be randomised to either a group that receives a multidisciplinary pain programme with the minimal interventional procedures, or a group receiving a multidisciplinary pain programme alone. The randomisation will be performed by a local research nurse in each of the participating pain clinics, using a computerised random number generator. The randomisation list is developed centrally. Therefore, the research nurse does not have any influence on the procedure and the treatment allocation is concealed. Randomisation will be stratified for the participating pain clinics. No treatment will be given prior to randomisation.In this pragmatic trial patients and care providers cannot be blinded. Because all outcome measures are self-reported by the patient, the outcome measurement is not blinded either. Data analysis will be conducted blinded for treatment allocation and blinding will only be finished after the final analyses have been concluded. To ensure data will be analysed anonymously, all patients will be assigned a unique number. To evaluate whether lack of blinding is associated with bias, expectations and preferences of patients will be measured before randomisation and after treatment allocation. Patient satisfaction will be measured after treatment and during follow-up.p < 0.05. Characteristics of patients with missing follow-up data will be compared to those with complete data to identify possible selective drop-out.Baseline data will be presented comparing the two treatment groups. Intention-to-treat analysis will be conducted for each follow-up moment. Missing data will be imputed with multiple imputation techniques ,57. The The economic evaluation will be performed according to the intention-to-treat principle and from a societal perspective. Costs of the minimal interventional procedures, physiotherapy, other health care utilization, patient and family costs, and costs of production losses will be measured and valued. Data are collected through self-completed cost questionnaires.Missing costs and effect data will be imputed using multiple imputation according to the Multivariate Imputation by Chained Equations procedure corrected and accelerated (Bca) bootstrapping with 5000 replications will be used to estimate confidence intervals around differences in total costs between treatment groups ,59.A cost-effectiveness and a cost-utility analysis will be performed. Incremental cost-effectiveness ratios will be calculated by dividing the difference in mean costs by the difference in the mean effects of the two treatment groups. Using a primary clinical effect measures of the trial, for instance pain intensity. Cost-utility will be based on the EQ-5D and expressed in costs per QALY. Uncertainty surrounding incremental cost-effectiveness and cost-utility ratios will be estimated using bootstrapping techniques and graphically presented in cost-effectiveness and cost utility planes. Cost-effectiveness acceptability curves and net monetary benefit will also be estimated. Sensitivity analyses on the most important cost drivers will be performed in order to assess the robustness of the results.The importance of this study is emphasized by the fact that a recent report did not show consensus regarding the effectiveness of minimal interventional procedures for low back pain . This isAt present, one of the applicants of this study protocol supervises three randomised, double-blind trials that evaluate the efficacy of 1) radiofrequency denervation of the first ramus dorsalis at L3, L4, L5 and S1 in patients with facet joint pain, of 2) radiofrequency denervation of the ramus communicans in patients with intervertebral disc pain, and of 3) radiofrequency denervation of the ramus dorsalis at L5, S1, S2 in patients with SI joint pain. These three trials are placebo controlled and do not include economic evaluations. The current trials will be the first on this topic including an economic evaluation.We did not choose to perform placebo-controlled experiments. However, because of the nature of the study, it was not desired to perform a placebo-controlled study either . FurtherBased on clinical experience we hypothesize that for patients with chronic mechanical low back pain, a multidisciplinary pain programme with minimal interventional procedures will be more effective than a programme without these procedures. The main expected effect is short-term pain reduction, but it is likely that this will be associated with improved functioning and quality of life. The costs of minimal interventional procedures are approximately  between €2500,- and €3500,- per treatment . We expeThis study will provide more knowledge on the treatment of chronic mechanical low back pain. Furthermore, results of this project will be included in future updates of the clinical guidelines of low back pain. The Dutch Association of Anaesthesiology supports this project and will use the results in a future update of their clinical guidelines. Finally, the results of this study will inform governmental policy regarding reimbursement of minimal interventional procedures for chronic mechanical low back pain. The results of the trials are expected to be available at the end of 2015.RCT: Randomized controlled trial; SI-joint: Sacroiliac joint; CVZ: Health insurance council; IASP: International association for the study of pain; ISIS: International spinal injection society; 4DSQ: Four-dimensional symptoms questionnaire; CPAQ: Chronic pain acceptance questionnaire; HADS: Hospital anxiety depression scale; PCI: Pain coping inventory; PCL: Pain cognition list; L: Lumbar vertebrae; IDET: Intradiscal electrothermal therapy; QALY: Quality adjusted life years; CEQ: Credibility/expectancy questionnaire; NRS: Numerical rating scale; ODI: Oswestry disability index; EQ-5D: EuroQol; MPI: Multidimensional pain inventory; PRODISC: Productivity and disease questionnaire; SD: Standard deviation.The authors affirm that this study has not received any funding/assistance from a commercial organization and we do not keep any commercial relationships which may lead to a conflict of interests. The Netherlands Society of Anesthesiologists (NVA) finances the data management for the studies. The NVA will use the data management programme for quality registration when the studies are finished. A member of the Netherlands Society of Anesthesiologists (Frank Wille) is represented in the project group.All authors have been involved in the development of the study design and research protocols. All authors read and corrected draft versions of the manuscript and approved the final manuscript.The pre-publication history for this paper can be accessed here:http://www.biomedcentral.com/1471-2474/13/260/prepub


Endoscopic discectomy method is a novel technique that is increasingly used in spine surgery. Previous studies have reported that some common complications like dural adhesions are lower in this technique compared with the other techniques. Furthermore, treatment outcomes are reportedly higher because of minimal invasion. Thepresent study aims to determine the outcome of percutaneous endoscopic discectomy.A total of 130 patients underwent the lumbar disc prolapse operations during 2008 to 2012 in all of them the entire procedure was performed endoscopically. All procedures were carried out from a posterior approach using a 4-mm Hopkins 0 degrees-telescope placed in the working insert equipped with channels for suction tube, operative instruments and nerve root retractor (ENDOSPINE instrumentation (Karl STORZ GmbH and Co. KG). The pre- and post-operation pain was assessed using a Visual Analog Scale (VAS). Furthermore, the treatment outcome was assessed using modified MacNab criteria before operation, 24 hours, one month, 2 months, 6 months, one year, and two years after operation . Good to excellent outcome was achieved in 89% of patients, which is comparable with the results of classic microdiscectomy. The mean age of patients was 35.6 years old and the mean length of follow-up was 3.4 years. There was significant reduction in the severity of back pain and lower limb symptoms at 6 months and 2 years post-operation. There was significant improvement in all aspects of the Quality of Life scores at 6 months and 2 years post-operation. In 3 patients the dural sac was lacerated but none of the tears was exceed a few mm in length with not association with neural injury.Findings of this study showed that percutaneous endoscopic lumbar discectomy is associated with improvement in back pain and lower limb symptoms. It has the advantage that it can be performed on a day case basis with short length of hospitalization and early return to work thus improving quality of life earlier.Endoscopic discectomy, Spine surgery, Lumbar disc prolapse operation, Outcome


The 5% Lidocaine patch is used for treating chronic neuropathic pain conditions such as chronic back pain (CBP), diabetic neuropathy and complex regional pain syndrome, but is effective in a variable proportion of patients. Our lab has reported that this treatment reduces CBP intensity and associated brain activations when tested in an open labelled preliminary study. Notably, effectiveness of the 5% Lidocaine patch has not been tested against placebo for treating CBP. In this study, effectiveness of the 5% Lidocaine patch was compared with placebo in 30 CBP patients in a randomised double-blind study where 15 patients received 5% Lidocaine patches and the remaining patients received placebo patches. Functional MRI was used to identify brain activity for fluctuations of spontaneous pain, at baseline and at two time points after start of treatment (6 hours and 2 weeks).There was no significant difference between the treatment groups in either pain intensity, sensory and affective qualities of pain or in pain related brain activation at any time point. However, 50% patients in both the Lidocaine and placebo arms reported a greater than 50% decrease in pain suggesting a marked placebo effect. When tested against an untreated CBP group at similar time points, the patch treated subjects showed significantly greater decrease in pain compared to the untreated group (n = 15).These findings suggest that although the 5% Lidocaine is not better than placebo in its effectiveness for treating pain, the patch itself induces a potent placebo effect in a significant proportion of CBP patients. Multiple lines of evidence suggest that aberrant activity in sodium channels contributes to chronic pain conditions that involve neuropathy. Blocking sodium channels such as with systemic Lidocaine reduces evoked intensity of acute pain -5 and alThe most advocated mode of Lidocaine administration is with 5% Lidocaine adhesive patches that are applied to the affected area and act by local absorption ,10. The It is not known whether the 5% Lidocaine patch has a true pharmacological effect on chronic back pain or if it is a potent placebo. Here we aimed to study how the 5% Lidocaine patch compares with a placebo patch in reducing pain of CBP and to investigate brain activity that can differentiate between the treatments. We hypothesised that pain and related brain activity will diminish more in participants in the active treatment arm. In a randomised double-blind, placebo controlled clinical trial, 30 CBP patients received drug or placebo treatment and underwent brain imaging to identify activity for fluctuations of spontaneous pain, at baseline and at two time points (6 hours and 2 weeks) after start of treatment. Moreover, we investigated inter-individual differences in pain responses to test whether a subset of patients is more responsive to Lidocaine treatment than placebo treatment.The chronic back pain intensity  and back pain properties  were compared between the two treatment groups at baseline, 6 hours, and 2 weeks post treatment using a repeated-measures two-way (drug and placebo treatment arms by sessions) repeated-measures analysis of variance (2-RM-ANOVA). The peak rating of spontaneous pain and the VAS scores were strongly correlated with each other , and since the spontaneous pain was collected during fMRI acquisition, we designated its peak pain rating as the pain intensity criterion for brain activity. Also note that at baseline, there was no significant difference (p ≫ 0.05) between the two groups in depression scores (BDI), anxiety scores (BAI) or neuropathic pain scores (NPS).2,89 = 7.8, p ≪ 0.001) but no treatment type effect , and no significant interaction between type and duration of treatment . At baseline, the lidocaine treated group did not show a significant difference in back pain magnitude from the placebo group  and 2 week period .There was a significant decrease in back pain magnitude with treatment duration , but there was no treatment type effect at 6 hours  or at 2 weeks  .As a next step, we tested the hypothesis that a subset of susceptible CBP patients benefits more from Lidocaine treatment than the placebo treatment. For this analysis, first all subjects were separated objectively into two groups based on a median split. The median of the absolute change in pain in all subjects was 29.4. Thus, all subjects that showed more than median change in pain were designated to the CBP decreasing and those less than median pain change were assigned to the CBP persisting groups. Next, we investigated whether the percent change in pain differed between Lidocaine and placebo treated subjects within a subset of patients. There were eight placebo and 7 Lidocaine treated CBP subjects that had reported a more than median (median = 29.4) decrease in pain after 2 weeks of treatment and the mean percent change = 61.4%, SEM = 2.04. In the remaining subjects  there were 7 placebo and 8 Lidocaine treated subjects and the mean percent change in this group was 3.9%, SEM = 0.13  was not significantly different  from the placebo treated group (59.7% SEM = 10.316). Moreover, pain related brain activity was not significantly different between the placebo and Lidocaine treated subjects within the CBPd subset with a less stringent fixed-effects contrast. Using the same technique, contrasting brain activity between the Lidocaine and placebo treated subjects within the CBPp group showed no significant difference between the two groups.observed, n =15) and the treatment group , at baseline and after two weeks. Within this time period, VAS rating for back pain significantly decreased for the CBP treatment but not for the CBP observed group  , 2) a borderline difference in age , 3) no difference in gender , and 4) no difference in depression , attesting to the close match between the treatment and observed CBP groups. Therefore, we conclude that the presence of the potential analgesic treatment within the clinical trial setting was critical for the decrease in back pain intensity observed after two weeks in the CBP treatment group.The effects of 5% Lidocaine patch were indistinguishable from the placebo patch, but one remaining question was the marked reduction in pain observed in both Lidocaine and placebo treated groups. A greater than 50% reduction in clinical pain in a large proportion of subjects represents a marked effect and this analgesia could have been caused by a number of factors associated with the experiment. For instance, the clinical trial setting, expectation of pain relief from a treatment and the twice daily application of the patch for two weeks may have acted as a potent placebo. Alternatively, the reduction in pain in the CBPd group may have been due to other disease related factors such as due to natural fluctuations in pain intensity. Therefore, we compared back pain between the observational group . Such a large number of chronic back pain subjects would be extremely difficult if not unachievable to recruit for an fMRI study. Nevertheless, additional studies are needed that test the effects of the 5% Lidocaine patch against a placebo to arrive at a solid conclusion regarding the efficacy of this treatment in chronic back pain.Recently, the 5% Lidocaine patch has emerged as first line therapy and since side effects are lower than oral or systemic doses, its use has become popular especially in geriatric populations. Our findings raise some important considerations since even though the 5% Lidocaine had no direct effect; the patch itself induces analgesia that is two to three folds higher than the accepted clinical level of 20% , but a discussion about the ethics of using placebos that produce strong analgesic effects is beyond the scope of the objectives of this study. This study brings to bear “the elephant in the room” issue relating to the ever present placebo effect in analgesic trials. This study also raises the need for more consideration into whether the clinical use of the Lidocaine patch in CBP is warranted. Overall, based on these findings, we conclude that the 5% Lidocaine patch has no drug mediated action on intensity of CBP; however, it does reduce pain intensity in more than 50% of subjects that is most likely due to a placebo effect. Our findings suggest that the patch is a potent agent for inducing placebo analgesia.A sample size of 30 subjects was predetermined based on a a review of literature ,38. A toAll subjects were right-handed and gave informed consent to procedures approved by the Northwestern University Institutional Review Board. Participants were compensated financially for their time. All patients, recruited by newspaper ads in Chicago area, were diagnosed with CBP by a clinician and had to fulfill a specific list of inclusion/exclusion criteria. Patients were included if they had CBP for ≫1 year, and a pain score ≫ 4/10 VAS at the baseline visit. Subjects were excluded if they suffered from co-morbidities, major psychiatric conditions or other medical conditions Table . PatientEfficacy for pain relief by 5% Lidocaine patch was tested in a randomised, double blind, placebo controlled longitudinal study. Of the patients recruited to this part of the study, data from 15 CBP patients that received the patches containing 5% Lidocaine and 15 age and sex matched CBP patients that received a patch containing the vehicle and no Lidocaine (placebo arm) were included in the analysis. Participants were randomly selected to receive drug or placebo. The Northwestern University Clinical Unit personnel generated the random allocation sequence using a random number generator, and held its key to the end of the study. All patients and experimenters  were blinded to type of treatment. The first application of the unlabeled patch was carried out by a clinician (blinded to type of treatment) who also explained the proper use of the patch. The patient was supplied with a measured number of unlabeled patches  and specific instructions were given to self administer the patch twice daily at 12 hour intervals for a period of two weeks. There was no difference in the appearance of the patches that contained Lidocaine or no drug.Each volunteer in this group participated in three experimental sessions. The first session was conducted immediately before start of treatment (baseline), the second session was performed 6 hours after application of the first set of patches and the third session was after 2 weeks of using the patches. At baseline, the patients filled out questionnaires related to their pain that included the McGill pain questionnaire (MPQ), neuropathic pain scale (NPS), Beck depression inventory (BDI) and Beck anxiety inventory (BAI). Before scanning, participants were trained on a finger-span device that was later used for acquiring continuous ratings of the fluctuations of spontaneous pain of CBP, on a numerical scale ranging from 0-100 during functional scans. This device was composed of a potentiometer the voltage of which was digitized and time-stamped in reference to fMRI image acquisition and connected to a computer providing visual feedback of the ratings ,40. In aAfter training, the subjects were placed in the scanner, T1-weighted structural images and fMRI data were collected while subjects performed pain or visual rating tasks In addition to the pain rating scan, a visual rating task scan was acquired in which the subject rated the length of the bar as it varied over time in conjunction with the subjects own pain ratings obtained in one of the preceding spontaneous pain rating scans.2, and number of sagittal slices = 160.fMRI data were acquired with a 3-T Siemens Trio whole body scanner with echo-planar imaging (EPI) capability using the standard radio-frequency head coil. Multislice T2*-weighted echoplanar images were obtained with the following parameters: repetition time (TR) = 2.5 s; echo time (TE) = 30 ms; flip angle = 90°, slice thickness = 3 mm, in-plane resolution = 64 × 64. The 36 slices covered the whole brain from the cerebellum to the vertex. A total of 244 volumes were acquired per condition in all participants and the first 4 volumes were discarded during the preprocessing step. A T1-weighted anatomical MRI image was also acquired for each subject using the following parameters: TR = 2.1 s, TE = 4.38 ms, flip angle = 8°, field of view = 220 mm, slice thickness = 1 mm, in-plane resolution = 0.86 × 0.86 mmSession 2 (6 hrs) and 3 (2 weeks) procedures were similar to session 1, patients filled out MPQ at all three time points. Some subjects had missing values in sensory and affective scores (n = 3 at 6 hour and n = 2 at 2 weeks) scores in the MPQ and were not included in corresponding statistical testing. This was followed by scanning procedures identical to those used at baseline.The CBP patients in the observational group received no treatment. They filled out the McGill Pain Questionnaire at baseline and after a two-week period. They too were trained on the finger span device and had fMRI scan at their second visit . For this group, change in back pain was assessed between baseline and the second visit, using the visual analog scale (VAS) of the MPQ questionnaire.http://www.fmrib.ox.ac.uk/fsl)]. The data pre processing were conducted using the FSL 4.1 [Image analysis to reveal significant brain activity based on changes in blood oxygen level-dependent (BOLD) signal was performed on each patient’s data using Functional Magnetic Resonance Imaging of the Brain (FMRIB) Expert Analysis Tool [. The chronic back pain intensity  and back pain properties  were compared between the two groups at all three scan sessions using a repeated measures analysis of variance.http://www.bic.mni.mcgill.ca/cgi/icbm_view/. Average group activity map was generated for 30 subjects to ascertain the region that corresponds significantly with spontaneous pain ratings. The next averaged map was generated by subtracting the visual activity maps from the pain activity maps with a paired t-test. Subsequently, averaged maps for each group (5% Lidocaine and placebo) were generated for the three time points. Furthermore, brain activation was contrasted between the Lidocaine and placebo group at all three time points using a random effects unpaired t-test analysis. These contrasts result in Z-score maps of statistically significant pain-related activity across different conditions. To correct for multiple comparisons, cluster-based corrections of the Z-statistic images were performed. The raw Z-statistic images from the group analysis were thresholded at Z-scores ≫ 2.3. For each resulting cluster of spatially connected voxels surviving the Z threshold, a cluster probability threshold of p ≪ 0.05 was applied to the computed significance of that cluster, which corrects for multiple comparisons according to Gaussian random field theory [Brain function in the two groups was assessed for each session for ratings of spontaneous pain and for visual control ratings. Ratings were binarized relative to the mean rating of spontaneous fluctuations of back pain  and convd theory . All imaTo investigate inter individual differences in treatment response we selected the 2 week period as the time point of interest and calculated change in pain from baseline. The median change was used to regroup CBP into persistent and decreasing (CBPp and CBPd). The questionnaire data was analyzed to assess differences between the two groups.The author(s) declare that they have no competing interests.JAH carried out statistical analysis and drafted the manuscript. MB carried out part of statistical analysis. LH participated in preprocessing fmri data, MC and EP participated in collecting data. TJS participated in study coordination and AVA conceived the study and participated in its design and coordination. All authors have read and approved the final manuscript.


Pain in infancy is a developmental process. Due to the underdeveloped pain pathways in the spinal cord, the threshold of stimulation and sensation of pain is low at birth and has potential impacts on increasing the central effects of pain. Primary trauma during infancy can cause long term changes in structure and function of pain pathways that continue until adulthood. Lack of pain management in children can result in morbidity and mortality.In this study we examined the duration of post-operative analgesia in children when clonidine is added to bupivacaine in caudal anesthesia.In this clinical trial, 40 children aged 1-8 years who were candidates for elective inguinal hernia repair were studied. Induction and maintenance of anesthesia were achieved using sodium thiopenthal, halothane and nitrous oxide. Children were randomly divided into 2 groups in a double-blind fashion, and were given caudal anesthesia with 0.125% bupivacaine (1ml/kg) alone or b bupivacaine plus 2 μg/kg clonidine. Blood pressure and heart rate were recorded peri-operatively. Analgesia was evaluated using objective pain scale (OPS) and sedation was assessed using Ramsay sedation scale (RSS). Acetaminophen was administered rectally for cases with OPS score greater than five.Duration of analgesia was found to be significantly longer in the group given bupivacaine plus clonidine (mean 417.50 min vs. 162.00 min).Peri-operative hypotension or bradycardia, post-operative respiratory depression, nausea or vomiting were not recorded in any patient.We concluded that addition of clonidine to bupivacaine prolongs the duration of post-operative analgesia without any respiratory or hemodynamic side-effects. Pain in infancy is a developmental process. Due to the underdeveloped pain pathways in the spinal cord, the threshold of stimulation and sensation of pain is low at birth and has potential impacts on increasing the central effects of pain. Primary trauma during infancy can cause long term changes in structure and function of pain pathways that continue until adulthood . Lack ofOpioids remain the mainstay for treatment of acute moderate to severe pain. But we can decrease their use by addition of other analgesics and use of techniques that target other parts of pain pathways and obtain an equal or even greater analgesia. Thus, decreasing adverse effects of opioids like nausea, vomiting, constipation, itching, respiratory depression and urinary retention .It shoulIn a survey on members of the British Pediatric Anesthesia Society, 58% stated that they have used additives in caudal block in children in order to prolong the duration of analgesia with no increase in the rate of complications such as loss of motion. The most common additives were ketamine, clonidine, fentanyl and diamorphone . ClonidiIn this study we examined the duration of post-operative analgesia in children when clonidine is added to bupivacaine in caudal anesthesia.In this randomized double-blind clinical trial, 40 ASA class I children aged 1-8 years weighing less than 20kg who were candidates for elective herniorrhaphy were selected. Patients were visited the night before the surgery. Parents were thoroughly informed about the study and gave an informed consent. Patients with a history of allergy to local anesthetics, those with coagulation disorders, spinal cord deformity, skin infection at the site of injection, and those with a history of metabolic, neurologic or cardiac diseases were excluded from the study. All patients received atropine and oral midazolam as premedication before transfer to the operating room. Patients in whom caudal block was diagnosed to be contraindicated for any reason by the anesthesiologist, were excluded from the study. Standard monitoring was performed for all patients. Anesthesia was induced using sodium thiopenthal 5-7 mg/kg and atracurium 0.5 mg/kg. Adequate dosage of halothane and a combination of nitrous oxide and oxygen with an equal proportion were used for maintenance of anesthesia.After induction of general anesthesia, the child was placed on his/her left lateral decubitus position. Caudal block was induced using 23-guage needle and after making sure that blood or CSF was not found in aspiration, anesthetic drug was injected. In order to select the medication for caudal block randomly and in a double blind fashion, the drug was prepared by another anesthesiologist by combining bupivacaine and normal saline and only the code of the drug was given to the researcher. In group 1 bupivacaine 0.125% 1 ml/kg along with clonidine 2 µg/kg (group BC) and in group 2 bupivacaine 0.125% 1ml/kg along with normal saline (Group B) were administered. The amount of normal saline in group 2 was similar to the amount of clonidine in group 1. If caudal block was unsuccessful or if the patient required more than 0.5 MAC of inhaled anesthetic for maintaining the adequate depth of anesthesia15 min after performing the block, the patient was excluded from the study.Patients received Ringer’s solution based on their weight and duration of operation peri-operatively and blood pressure (BP) and heart rate (HR) were recorded every 5 minutes. Any decrease in BP and HR for more than 20% compared to the pre-operative values was considered as hypotension and bradycardia and treated with quick infusion of fluids and atropine, respectively. Any increase in BP and HR for more than 20% of the pre-operative values was considered as inadequate analgesia and was treated with fentanyl 1µg/kg if necessary. After completion of surgery, patients were transferred to the recovery room awake and were evaluated in terms of pain and sedation using Objective Pain Scale and Ramsay Sedation Scale, respectively. Assessments were made immediately after the transfer and then every 15 minutes until they were ready to leave the recovery room. For pain scale greater than 5, analgesics were administered and the time of administration was recorded. After transferring to the ward, if the patient did not need analgesics in the recovery room, pain was assessed in the ward, and for pain scale over 5, analgesics were given and recorded. If the patient did not require analgesics for 24 hours, it was registered under the category of no necessity for analgesics.The time interval between the conduction of caudal block and time of receiving the first dose of analgesic was considered as duration of post-operative analgesia. Researchers followed the ethical principles of Declaration of Helsinki in all steps and patients’ name and personal information remained confidential. Data collected were analyzed using SPSS version 11.5 software (Microsoft). Prevalence of variables was determined using statistical tests. For comparison of quantitative variables between the 2 groups, student t test and for qualitative variables Chi square test was used.In this study a total of 40 children were evaluated in 2 groups of 20 each. Two patients were excluded from the study and replaced due to having spinal cord deformity. The mean time of extubation was 7.50 (2-15) min in group B and 4.45 (2-10) min in group BC. This difference was statistically significant  before induction of anesthesia was 88.35 (75-112) mmHg in group B and 85.55 (70-98)mmHg in group BC . The meaIn this study, 40 ASA class I children aged 1-8 yrs. and weighing less than 20 kg who were candidates for elective herniorrhaphy were evaluated. We found that addition of clonidine to bupivacaine in caudal block prolongs post-operative analgesia with no side effects (417.5 min in group BC versus 162 min in group B). This finding was in accord with most of the similar previous studies. In the present study we used bupivacaine 0.125% for caudal block which had been reported to cause adequate analgesia without loss of motion . Caudal Addition of clonidine in caudal block has proved to be safe in various studies. In a report published in 2008 in 3 pediatric patients who received one hundred times the standard dose of caudal clonidine, despite severe drowsiness for 24 hours, respiratory depression, decrease in oxygen saturation, need for oxygen administration or hemodynamic instability were not observed . This inOur study was different from that of Akin et al. in that they used caudal clonidine in one group and intravenous clonidine with the same dose of 2 µg/kg in another group. However, our study results were in accord with theirs and in both studies those receiving caudal clonidine had the longest duration of post-op analgesia. El-Henawy et al. in 2009 performed a study on 60 children aged 6 months to 6 years and evaluated the effect of addition of clonidine or dexmedetomidine to caudal bupivacaine . They demonstrated that addition of clonidine or dexmedetomidine to caudal bupivacaine significantly prolongs the analgesia in pediatric patients undergoing infra-abdominal surgeries with no increase in the incidence of side effects. Also, they showed that clonidine and dexmedetomidine had no advantage over each other . Our stuYildis et al. in 2005 performed a study on 60 children aged 1-10 yrs. who were candidates for elective herniorrhaphy. Patients were divided into 4 groups. In group 1, bupivacaine 0.125%, 1 ml/kg alone and in groups 2, 3 and 4 bupivacaine along with 1, 1.5 and 2 µg/kg clonidine, respectively were used for caudal block. They showed that duration of analgesia was significantly longer in the group receiving 2 µg/kg clonidine and peri-operative hypotension or bradycardia, and post-operative respiratory depression or loss of motion did not occur in any patient . The onl


The symptom ‘dizziness’ is common in patients with chronic whiplash related disorders. However, little is known about dizziness in neck pain patients who have not suffered whiplash. Therefore, the purposes of this study are to compare baseline factors and clinical outcomes of neck pain patients with and without dizziness undergoing chiropractic treatment and to compare outcomes based on gender.This prospective cohort study compares adult neck pain patients with dizziness (n = 177) to neck pain patients without dizziness (n = 228) who presented for chiropractic treatment, . Patients completed the numerical pain rating scale (NRS) and Bournemouth questionnaire (BQN) at baseline. At 1, 3 and 6 months after start of treatment the NRS and BQN were completed along with the Patient Global Impression of Change (PGIC) scale. Demographic information was also collected. Improvement at each follow-up data collection point was categorized using the PGIC as ‘improved’ or ‘not improved’. Differences between the two groups for NRS and BQN subscale and total scores were calculated using the unpaired Student’s t-test. Gender differences between the patients with dizziness were also calculated using the unpaired t-test.Females accounted for 75% of patients with dizziness. The majority of patients with and without dizziness reported clinically relevant improvement at 1, 3 and 6 months with 80% of patients with dizziness and 78% of patients without dizziness being improved at 6 months. Patients with dizziness reported significantly higher baseline NRS and BQN scores, but at 6 months there were no significant differences between patients with and without dizziness for any of the outcome measures. Females with dizziness reported higher levels of depression compared to males at 1, 3 and 6 months .Neck pain patients with dizziness reported significantly higher pain and disability scores at baseline compared to patients without dizziness. A high proportion of patients in both groups reported clinically relevant improvement on the PGIC scale. At 6 months after start of chiropractic treatment there were no differences in any outcome measures between the two groups. The complaint of neck pain is second only to low back pain in terms of common musculoskeletal problems in society today with a lifetime prevalence of 26-71% and a yearly prevalence of 30-50% . Apart fGender differences in reporting pain intensity is currently a topic of debate. Recent research suggests that females report more pain because they feel pain more intensely than males over a variety of musculoskeletal complaints ,11. FurtTherefore, the purposes of this study on neck pain patients receiving chiropractic care are twofold: 1. to compare baseline variables and the clinical outcomes of neck pain patients with and without dizziness in terms of clinically relevant ‘improvement’, pain, disability, and psychosocial variables over a 6-month period; 2. to evaluate gender differences for neck pain patients with dizziness in terms of clinically relevant ‘improvement’, pain, disability, and psychosocial variables in a longitudinal study.This is a prospective cohort study with 6 month follow-up. Ethics approval was obtained from the Orthopaedic University hospital Balgrist and Kanton of Zürich, Switzerland ethics committees (EK-19/2009) and written informed consent was obtained from all patients.Consecutive new patients over the age of 18 with neck pain of any duration who had not undergone chiropractic or manual therapy in the prior 3 months were recruited from multiple chiropractic practices in Switzerland. All 280 members of the Swiss Association for Chiropractic were invited to participate in the study and 81 practitioners from both the German and French geographic regions of Switzerland chose to enrol patients. There were no set number of patients required from participating clinicians and all chiropractors were strongly encouraged during meetings and with frequent e-mail reminders to enrol all qualifying patients. Patients with specific abnormalities of the cervical spine that are contraindications to chiropractic manipulative therapy, such as tumours, infections, inflammatory arthropathies, acute fractures, Paget’s disease, cervical spondylotic myelopathy, known unstable congenital anomalies and severe osteoporosis, were excluded. Additionally, patients on anticoagulation therapy were also excluded.Information provided by the treating chiropractor at the initial consultation included: patient age, gender, marital status, whether or not the onset of pain was due to trauma, whether or not the patient smokes, whether or not the patient was currently taking pain medication, duration of current complaint, number of previous episodes, whether or not the patient also complained of dizziness and the patient’s general health status . This information was completed on a baseline information form. For dizziness, patients were asked to report if they currently experienced ‘dizziness’ which was described as feelings of ‘light-headedness’ or faintness or disorientation or unsteadiness or reduced postural and balance control that was related to their neck pain.The eleven point numerical rating scale (NRS) for current neck pain  and a separate NRS for current arm pain as well as the Bournemouth Questionnaire for neck (BQN) disability, were administered to the patient immediately prior to the first treatment by the office staff of each practice. The BQN is a multidimensional instrument covering 7 domains with each domain evaluated using an 11-point numerical rating scale (0 through 10). The seven domains include: (i) pain; (ii) disability (activities of daily living (ADL)); (iii) disability ; (iv) anxiety; (v) depression; (vi) work, both inside and outside the home, fear avoidance; and (vii) locus of control. Each domain is evaluated independently on an 11 point scale with 0 indicating ‘not at all affected’ and ‘10’ indicating ‘maximally affected’. In addition to each domain score, the total score (maximum 70 points) is also calculated. The BQN has been translated and validated in both German and French with the seven domains as well as the over-all score having been shown to be more sensitive to change in a patient’s condition compared to other similar outcome measures ,14.Telephone interviews were conducted 1, 3 and 6 months after the first chiropractic treatment to collect the outcome data. The primary outcome of ‘improvement’ for both neck pain and the symptom of ‘dizziness’ was evaluated using the Patient’s Global Impression of Change (PGIC) scale  for the Additionally, data from the NRS (neck), NRS (arm), and the BQN were also collected as secondary outcome measures at 1 month, 3 months and 6 months after the start of treatment via telephone interviews , NRS (arm), BQN subscale and BQN total scores were done using the unpaired Student’s t-test. Male and female patients with and without dizziness were compared for the proportion reporting ‘improvement’ on the PGIC scale at 1, 3 and 6 months and the Chi-squared test was used to investigate a gender difference in ‘improvement’. The unpaired t-test was also used to compare the follow-up NRS and BQN scores between the genders. Within gender differences in follow-up NRS and BQN scores compared to baseline scores were assessed using the paired t-test.Four hundred and five neck pain patients with baseline data who had consented to be part of the Chiropractic Outcome Study in Switzerland were included in this study. Eighty-one or 29% of the 280 members of the Association of Swiss Chiropractors recruited patients for this study from the two largest geographic regions of Switzerland (German and French). Of the 405 patients, 177 (44%) reported neck pain and related dizziness while 228 reported that they had neck pain without dizziness. Baseline demographic factors comparing patients with and without dizziness are shown in Table At baseline neck pain patients with dizziness reported statistically significantly higher levels of neck pain, arm pain, physical and social disability, anxiety, depression, work fear avoidance and less control over their pain condition (locus of control) compared to those without dizziness. As a result, the BQN total scores were significantly different between those with and without dizziness, being significantly higher in neck pain patients with dizziness p = 0.0001)  with 133 of the 177 patients stating that they had neck pain and dizziness being female (75%). Comparing male and female patients with and without dizziness, there were no significant gender differences for age, duration of complaint, presence of radiculopathy, trauma onset, smoking, general health or baseline report of neck pain or arm pain. Females with and without dizziness reported significantly higher baseline scores for ‘depression’ compared to males with and without dizziness, with the scores being higher in the patients with dizziness compared to those without.There was no significant difference in the proportion of males and females with and without dizziness who improved at any time point and both genders with and without dizziness reported significantly improved NRS and BQN scores compared to baseline at all follow-up time points. Table without dizziness, females reported higher levels of depression only at 3 months compared to males. For patients with dizziness however, depression levels continued to be rated significantly differently between the genders at all follow-up time points, with higher scores in female patients  were counted as clinically relevant improvement. ‘Slightly better’ was not considered to be improved in order to error on the side of caution ,17. StatIt is important to point out that at baseline neck pain patients with dizziness reported significantly higher scores for severity of neck pain, arm pain, all subscales on the BQN as well as the BQN total score compared to the neck pain patients without dizziness. However, over time fewer differences between these two groups were found with no significant differences between the two cohorts at the 6 month data collection time point. Depression and social disability were the two categories that remained significantly different at one and 3 months. However, although significant, the mean scores at 3 months of 1.35 and 0.81 for depression and 0.83 and 0.43 for social disability are very low on the 11 point BQN subscales so it can be suggested that these differences are clinically unimportant. The BQN subscale ‘depression’ stood out as the most dramatic difference between patients with and without dizziness as well as between males and females with and without dizziness. It was nearly 2 points higher in the patients with dizziness at baseline but also demonstrated the most dramatic change score at 6 months of nearly 3.5 points. At that time point the mean score was no longer significantly different compared to patients without dizziness.It was somewhat surprising to find that nearly 44% of neck pain patients presenting to Swiss chiropractors stated that they had associated dizziness. However, the fact that 75% of neck pain patients with dizziness in this study were female is not surprising. It is well documented that females are more likely to suffer from neck pain in general -12 and tCervicogenic dizziness or dizziness of suspected cervical origin with or without unsteadiness can arise from mechanical, degenerative, inflammatory or traumatic problems affecting various structures of the neck . In partTherefore it is hypothesized that manual therapy such as spinal manipulation may be effective in treating cervicogenic dizziness by restoring normal movement of the zygoapophyseal joints, reducing pain and muscle hypertonicity and thereby restoring normal proprioceptive and biomechanical functioning of the cervical spine ,21. IndeLimitations to this study must start by stating that because this was not a randomized clinical trial the favourable results reported here cannot be attributed to the chiropractic treatment. There was also no attempt to compare outcomes based on the specific treatments applied or the frequency of treatment. Additionally, acute vs. chronic patients were not evaluated separately because no difference in duration of complaint was found between those with and without dizziness. It is well known that most acute neck pain patients improve due to natural history. Neck pain is most likely recurrent however, and as such, the improvement noted by these patients may very well be noteworthy. Another limitation to this study may be that there were fewer patients with 6 month data compared to baseline data. This was primarily due to the fact that this is an ongoing study and the time point had not yet been reached for the 6 month telephone call. However, with 121 patients with baseline dizziness and 176 patients without dizziness at baseline for the 6 month data collection time point, additional patients would be unlikely to alter the results .The fact that only 29% of practicing chiropractors contributed patients to this study may also be a limitation as it is unknown whether or not this sample is representative of the greater chiropractic population. Additionally, some chiropractors contributed several patients and others only a few. It is known however, that chiropractors from the two largest geographic regions of Switzerland submitted patients and that those participating had a wide range of practice experience. Additionally, all Swiss chiropractors must complete a two year full time post-graduate residency programme with a fairly standardized curriculum and pass a rigorous post-graduate examination in order to practice as independent chiropractors in this country. It is known from the Swiss job analysis study published in 2010 that the ‘diversified’ manipulative technique is applied to the majority of patients by the vast majority of chiropractors. Additional commonly applied therapies include trigger point therapy, advice on activities of daily living, therapeutic exercises and mobilization techniques . Thus diFinally, the use of multiple, uncorrected statistical tests may be another limitation to this study. In particular the large number of statistical tests used in this study may have resulted in a chance-statistically significant finding (one significant finding per 20 tests if p < 0.05). Further exploration of predictors of improvement for neck pain patients with dizziness should use multiple regression analysis.A high proportion of patients with and without dizziness reported clinically relevant improvement at 1, 3 and 6 months. Although neck pain patients with dizziness undergoing chiropractic treatment reported significantly higher pain and disability scores at baseline compared to neck pain patients without dizziness, there were no significant differences in any outcome measures between the two groups at 6 months after start of treatment. Neck pain patients with dizziness were much more likely to be female and females with dizziness report higher levels of depression compared to males with dizziness at all data collection time points.The authors declare that they have no competing interests.BKH: Concept and design of the study, analysis and interpretation of data, drafting and revising the manuscript, final approval of the manuscript. CKP: Collection and entry of data, analysis and interpretation of data, drafting and revising the manuscript, final approval of the manuscript.


Objectives: The purpose of this study was to compare the effect of PSA block injection with infiltration technique regarding local anesthesia for surgical extraction of upper third molar.Material and Methods: A prospective, intra individual, single-blind randomized controlled trial was designed to study the severity of pain during injection and after surgical extraction of the bilaterally and symmetrically similar upper third molar in a total of 53 patients, in addition to evaluating the need to repeat the injection and requirement of post operative anti-inflammatory tablets.Result: Although the average pain score for all studied times in PSA side was lower than the average pain score in infiltration technique, repeated statistical measures demonstrated that no significant pain reduction occurred in the two techniques.Conclusion: The both tested methods have the same statistic equivalence for the surgical extraction of maxillary third molars. Key words:Surgical extraction, maxillary third molars, PSA block, infiltration. Surgical extraction of impacted teeth can be either uneventful and uncomplicated, or difficult, with considerable postoperative pain.  MaxillarA range of local anesthetic drugs have been used in dentistry among which lidocaine is the most popular . The comThe majority of the recently published articles evaluate the anesthetic efficacy of the PSA nerve block and maxillary infiltrations either in inflamed pulps or in the normal tooth extraction -8. To th- Data SamplingThis prospective, intra individual, single-blind, randomized controlled trial study was undertaken between September 2009 and June 2010 at the Department of Oral and Maxillofacial Surgery, College of Dentistry, SIUST University. A total of 53 patients, 31(58.4%) males and 22(41.5%) females who underwent a surgical removal of symmetrically bilaterally impacted upper third molars due to prophylaxis or orthodontic purpose with a mean age of 20. 4 ± 3 at the time of surgery, ranged between 17 and 26 years. All the patients who were healthy and non-Smokers having no medications or oral contraceptives in the preoperative period and were free from active local inflammatory lesions, were included in the analysis. The study design was approved by the Research and Ethics Committees of University. All patients were informed as to the nature of the surgical and experimental procedures, and informed consent being obtained before surgery.An orthopantomographic images were used to ensure the symmetry of the type of impaction and to classify all the impacted maxillary third molars into mesioangular 27 50.9%), vertical 15(28.3%) and distoangular 11(20.7%) impactions based on Winter`s classification %, vertic. In all - ProceduresEach of the 53 patients was scheduled to undergo bilaterally and symmetrically identical upper third molar surgical extraction .The two extractions were performed in two separate sessions approximately 4 weeks apart to allow for total recovery from the first one.In each patient, the choice of which anesthetic techniques were going to be administered, the PSA block technique and on the contra lateral the infiltration technique, was made randomly. The palatal injection was combined to both techniques. A topical anesthetic gel 5% lidocaine  was placed with a cotton tip applicator. After reaching the target area, aspiration was performed several times during the administration of the injection using standard dental aspirating syringe  fitted with a 25-gauge, long, 0.40×35mm needle . The technique of the PSA block was identical to Malamed`s text . In the The surgical procedure was similar in all cases and was performed by the same surgeon using a standardized technique under local anesthesia without any kind of sedation ; full envelop mucoperiosteal flaps were elevated prior to the removal of the third molars. Alveolotomy was carried out using a bur under a concomitant continuous spray of sterile saline solution; the flaps are sutured with a 4-0 silk suture.After surgery, all of the patients received an oral non-steroidal anti-inflammatory drug (600 milligrams of Ibuprofen every 4-6 hours for four days) and topical chlorhexidine digluconate for seven days .The suture material was removed after one week. All surgical details were noted in a pre-made questionnaire- Pain MeasurementPreoperative pain assessed by a single blind professional operator was different from the surgeon who performed the surgery, repeating each record three times on each case: during the injection, at the end of operation and after 15 minutes from the end of operation, using a 170-mm Heft-Parker visual analog scale  statistical software package. The pain VAS scores were analyzed by analysis of variance (ANOVA) for repeated measures. X2 were used for significance of age, sex and operation time on the severity of pain .Probability less than 0.05 was considered statistically significant.In a total of 53 patients participated in this study, there was no significant correlation between age and sex with the intensity of pain.The average duration of the surgical procedure starting from the flap reflection to the end of suturing on the PSA side, was 7.83± (4.18) minutes ; while on the infiltration side, it was 8.47± (4.38) minutes , the difference was statistically significant F=21.701 (P<0.01) with intensity of pain. Evaluations at injection showed a 1 (1.8%) positive aspiration with PSA block and without any positive aspiration with infiltration technique.Although the average pain score for all studied times in PSA side, was lower than the average pain score in infiltration technique, repeated-measures ANOVA demonstrated no significant difference in pain reduction between the two techniques (P > 0.05, We did not note any significant differences between the PSA side and the infiltrations side in terms of needing for a second or third injection, P=0.096 but little increase in the frequency of repeating injection on the infiltration side was observed.The protocol of study also involved assessing NSAID intake in the first three hours. The mean consumption of ibuprofen in number of tablets is noted in Fig. The improvements in agents and techniques for local anesthesia improve the patients` perceptions, comfort and acceptance during dental treatment. The pain control is an important factor for reducing the fear and anxiety associated with dental procedures  for thatMaxillary infiltration anesthesia is a common method to anesthetize maxillary teeth . Also thIn the current study, the success of maxillary PSA block and infiltration technique have been evaluated using the VAS while in the previous studies -17 they According to the findings of the present comparative study, it can be concluded that there was no difference in the pain experienced by patient using either PSA nerve block technique or infiltrations technique,in surgical extraction of maxillary third molars during the injection or in the post surgical periods , Fig. 2.There were positive blood aspirations during the PSA in the observation of Pfeil et al. , but ourPreventive strategies for postoperative management of pain and inflammation are based on the known ability of NSAIDs to block the arachidonic acid cascade but concurrent use of NSAIDs should be avoided when possible because of the risk of producing gastrointestinal tract hemorrhage . In thisPSA block was used to overcome the variation in the anatomy of the roots and nerve pathways or even in the presence of infection . Some adIn conclusion, the statistical analysis of the study results has confirmed clinical equivalence for the surgical extraction of maxillary third molars with PSA nerve block and infiltration technique with the mean advantages of PSA that Minimum number of necessary injections but the risk of a potential complication also must be considered whenever the PSA block is used.


Many intensive care unit (ICU) patients describe pain and other adverse feelings that may impact long-term psychological morbidity. Sympathetically mediated palmar skin conductance variability is related to emotionally induced perspiration and correlates with pain levels in the perioperative setting but has not been studied in ICU patients.®. The number of skin conductance fluctuations per second (NSCF) was measured in parallel with bedside observation during one hour of intensive care, including rest, procedures and patient-staff interactions. Arousal-agitation level was monitored with the motor activity assessment scale (MAAS). Pain was monitored with the numeric rating scale (0 to 10) in patients able to communicate or by observation in patients unable to communicate.Twenty non-intubated and 20 intubated general ICU patients were included in this observational study. Patients were monitored with the MED-STORM Pain Monitoring SystemP = 0.002). An interaction effect was found, with increased NSCF response to stimulation/pain with increasing MAAS (P < 0.001).In non-intubated patients, NSCF increased with increasing stimulation/pain but also with higher MAAS (P < 0.001). In contrast to non-intubated patients, no difference in NSCF between MAAS levels was found for any given degree of stimulation in intubated patients.In intubated patients, NSCF increased significantly with increasing stimulation/pain (In critically ill patients, NSCF may be more useful evaluating emotional distress rather than pain alone. It needs to be assessed whether NSCF monitoring is clinically useful and whether controlling emotional distress with the aid of such monitoring may impact on patient care and outcomes. Clinical practice guidelines for sedation and analgesia have been developed in order to achieve and maintain comfort and safety in critically ill patients . Still, Emotional stress is associated with increased activity in the sympathetic nervous system. This increased activity includes the activation of palmar sweat glands . Sweat gIn order to measure ongoing palmar sweat gland activation in response to emotional stress, a measure of skin conductance variability  has recently been developed and evaluated ,8. In a To our knowledge, skin conductance variability has not been evaluated as a measure of pain in critically ill adults. We performed this observational study in order to explore the relationship between skin conductance variability (referred to as NSCF) and varying degrees of stimulation, pain and level of arousal-agitation in a mixed ICU patient population.This prospective observational study was performed at the general ICU, a mixed medical and surgical ICU at Karolinska University Hospital Solna, Stockholm. The study was approved by the local Ethical Review Board in Stockholm . Forty critically ill patients age above 17 years, were included (20 non-intubated and 20 intubated). Patients were excluded if they were diagnosed with neuro- or myopathy, were receiving neuromuscular blocking agents, or were treated with atropine or glycopyrrolate the same day, as such treatments or conditions could potentially make clinical assessment difficult or affect muscarinic sweat gland receptor activity. Written informed consent from the participants or their closest relatives was obtained.®  was used for this purpose. Three single use Ag/AgCl electrodes  were attached to the palmar surface of the patient's hand: on the thenar eminence (current electrode), hypothenar eminence (measurement electrode) and just below the second and third digits (reference electrode). The hand least likely to be moved was chosen to minimize movement artifacts. Skin conductance variability was measured by alternating current at 66 Hz and an applied voltage of 50 mV.Skin conductance variability was monitored during one hour of routine daytime intensive care nursing and treatment. A skin conductance monitor, Med-Storm Pain Monitoring SystemSkin conductance variability was measured as the number of skin conductance fluctuations per second (NSCF). The cutoff for identifying skin conductance fluctuations was set with skin conductance troughs and peaks of an amplitude > 0.02 microsiemens (μS), as in previous studies of NSCF in the perioperative setting -11. The Parallel with NSCF monitoring, the level of stimulation/pain and arousal-agitation were assessed.For awake and communicative patients, pain level on the 11-point numeric rating scale (NRS 0 to 10)  was askeObservations of stimulation/pain were categorized in four groups:A. No stimulation. The patient was lying undisturbed, without any observed or reported pain (see D).B. Mild stimulation without observed or reported pain. The patient was being spoken to or procedures, such as gentle washing, were performed or the patient made slight movements without observed or reported pain.C. Potentially painful stimulation without observed or reported pain. The patient did not report or show signs of pain but was exposed to any of the following procedures or conditions:1. Needle stick.2. Turning of the patient.3. Suction of the mouth, hypopharynx or endotracheal tube.4. Unsynchronized with the ventilator or abnormal breathing pattern.5. Dressing of wound.D. High pain rating or overt expression of pain in rest or during stimulation/procedure. The patient expressed pain verbally (NRS above 3). If the patient could not rate pain with the NRS the following signs were considered indicative of pain or discomfort:1. Facial grimacing.2. Moaning or groaning.3. Localizing painful area, withdrawing from touch or resisting potentially painful movement or procedure.Patients' arousal/agitation level was assessed with the Motor Activity Assessment Scale (MAAS) scale Table  13], th, th13], During the hour of monitoring, typical procedures were washing, turning the patient, physiotherapy and in some cases also invasive procedures, such as intravenous line insertion or bronchoscopy. At the time of the event or procedure, an on-line mark on the laptop monitor was made and the NRS or observed stimulation/pain level and MAAS level was noted. Comments describing the event or procedure were made for each observation. The mean NSCF value, representing the 15-second window at the time of the event, was later extracted for analysis. When the skin conductance signal quality was below 80%  or connection was temporarily lost, the event was registered as "artifact", as were situations when the patient moved the NSCF measurement hand.P < 0.01. Analyses were performed with Stata version 12 .Unlike the non-intubated patients, the intubated patients could not speak and more often received sedative and opiate infusions. The intubated and non-intubated patients were, therefore, analyzed separately. Random-effects regression models were used to analyze NSCF over different pain and MAAS levels. In the regression models, stimulation and MAAS were introduced as numeric variables. Statistical significance level was set at Patient demographics are presented in Table P = 0.002) for all MAAS levels except MAAS 2 , with an increased NSCF response to stimulation with increasing MAAS  at all MAAS levels   Figure .Artifacts precluded adequate registration 83 times (11.3% of observations) in the intubated patients and 206 times (28.8% of observations) in the non-intubated patients.To our knowledge, this is the first study evaluating skin conductance variability in critically ill adult patients. The main findings were that NSCF generally increased with the degree of stimulation/pain, an observation common for both patient groups.The highest NSCF readings were found in non-intubated patients with high MAAS level and with overt expression of pain. A higher degree of arousal or agitation was associated with a stronger NCSF response to stimulation/pain Figure . This fiP = 0.64). One difference between study groups, besides endotracheal intubation, was that the intubated patients received more sedatives and analgesics . In some patients the electrodes fell off due to movement and stretching of the wires, or due to excessive sweating. Electrode adhesion problems and movement artifacts may possibly be reduced with better electrodes and wrapping of the hand .Generally, we interpret our study findings as that NSCF appears to mirror distress rather than pain alone, which is a limitation from a pain monitoring perspective. Instead, skin conductance variability monitoring might be a means of monitoring discomfort or distress in ICU patients. The level of comfort and sedation, as well as sedative choice may affect memories from the ICU ,18, and A major limitation in our study was our classification of stimulation/pain in non-communicating patients. At the outset of the study, we did not have a validated Swedish pain monitoring instrument available. We used a non-standardized way of assessing pain in these patients, namely by observing facial grimacing, body movements or sounds as indicators of pain in patients unable to communicate verbally, which may have led to some degree of misclassification. Recently, pain monitoring instruments for poorly communicating patients have been developed and validated ,21, withAnother limitation is that the study observers were not blinded for online NSCF levels. The monitor was new for the observers and we felt that information displayed was important in this pilot study. Online information included electrode status and signal quality, the time marker and online "notepad". For a more formal validation study, including specificity and sensitivity analyses, a validated pain assessment tool or a composite pain and agitation score would be appropriate to use, as well as blinding of skin conductance levels.Finally, while NSCF has been shown to decrease with analgesic treatment of pain in postoperative patients , our proPalmar skin conductance variability increases with increasing stimulation in critically ill patients. In non-intubated patients increasing MAAS levels are associated with increased NSCF responses to stimulation/pain. This interaction is not seen during mechanical ventilation and sedation. Future studies of skin conductance variability are needed, to investigate if skin conductance variability monitoring can aid ICU clinicians in the general management of emotional stress due to pain and other adverse feelings, and if such monitoring and subsequent interventions are associated with improved patient outcomes.• Skin conductance variability as measured as NSCF, increases with increasing stimulation/pain in critically ill ICU patients.• In less sedated and non-intubated ICU patients, increasing arousal and agitation increases the NSCF response to stimulation.• Further research is warranted to investigate potential clinical benefits of NSCF monitoring in ICU patients.μS: microsiemens; ICU: Intensive Care Unit; MAAS: Motor Activity Assessment Scale; NRS: numeric rating scale; NSCF: number of skin conductance fluctuationsHanne Storm has a potential competing interest as a part owner, CEO and share-holder in Med-Storm Innovation AS, and has contributed to the development of the skin conductance monitor used in the study. Med-Storm Innovation AS has patents on the skin conductance equipment used in this study for measuring pain and sedation level. The other authors report no competing interests.AG, PS, AS, HS and PR contributed to the conception and design of the study. AG, AS and PS collected data. AG, PS, PR, MB and HS participated in data analysis and interpretation. AG and PS drafted the manuscript and all authors were involved in the revision and final approval of the submitted manuscript.


Incorporating the patient's view on care and treatment has become increasingly important for health care. Patients describe the variety of consequences of their chronic pain conditions as significant pain intensity, depression, and anxiety. We hypothesised that intensities of common symptoms in chronic pain conditions carry important information that can be used to identify clinically relevant subgroups. This study has three aims: 1) to determine the importance of different symptoms with respect to participation and ill-health; 2) to identify subgroups based on data concerning important symptoms; and 3) to determine the secondary consequences for the identified subgroups with respect to participation and health factors.This study is based on a cohort of patients referred to a multidisciplinary pain centre at a university hospital  in Sweden. The patients answered a number of questionnaires concerning symptoms, participation, and health aspects as a part of the Swedish Quality Registry for Pain Rehabilitation (SQRP).Common symptoms  in patients with chronic pain showed great variability across subjects and 60% of the cohort had normal values with respect to depressive and anxiety symptoms. Pain intensity more than psychological symptoms showed stronger relationships with participation and health. It was possible to identify subgroups based on pain intensity, depression, and anxiety. With respect to participation and health, high depressive symptomatology had greater negative consequences than high anxiety.Common symptoms (such as pain intensity and depressive and anxiety symptoms) in chronic pain conditions carry important information that can be used to identify clinically relevant subgroups. Chronic pain is influenced by and interacts with physical, emotional, psychological, and social factors and often results in significant suffering Many interventions in clinical practice and in research for patients with chronic pain have pain intensity as one important (primary) outcome variable. However, in the systematic reviews of multimodal (multidisciplinary) pain rehabilitation (MMPR) presented by the Swedish Council on Health Technology Assessment (In Swedish: SBU), only a minority of the included studies had pain intensity as an outcome Patients with chronic pain are often regarded as a homogenous group . Hazard et al. stated that such an approach yields results of debatable clinical importance There is little doubt that pain often is co-morbid with psychological conditions We hypothesised that intensities of common symptoms in patients with chronic pain conditions carry important information that can be used to identify clinically relevant subgroups. Using data collected from a continuous flow of patients to a multidisciplinary pain centre at a university hospital in Sweden, this study addresses following aims:To determine the relative importance of different symptoms with respect to participation and perceived ill-health;To identify subgroups based on data concerning important symptoms; andTo determine the secondary consequences of the identified subgroups with respect to certain participation and health factors.This study is based on a cohort of patients referred to the Pain and Rehabilitation Centre at the University Hospital, Linköping, Sweden between 2005 and 2008. During this period, 4645 patients were referred to the centre and 4069 of these reported to the Swedish Quality Registry for Pain Rehabilitation (SQRP) (88% participation). Before the first assessment, all patients gave their written informed consent. After receiving written information about the study, all subjects signed a consent form that was in accordance with the Declaration of Helsinki. The study was granted ethical clearance by the Linköping University Ethics Committee (Dnr: 97139).The Swedish Quality Registry for Pain Rehabilitation (SQRP) is a registry based on a questionnaire that is answered by all patients with chronic pain. The questionnaire is given to these patients the first time  they are admitted to the specialist care of the Pain and Rehabilitation Centre in the County Council of Östergötland, Sweden. For patients participating in MMPR, questionnaires are also answered directly after and at a 12-month follow-up (not reported in this study).On a national level, the SQRP has aggregated data since 1998 and now compares all patients referred to the majority of Swedish clinical departments of rehabilitation. Approximately 20 clinical departments  are included, which means that 80% of all clinical departments of rehabilitation at the specialist level in Sweden provided data for this study. The main purpose of the SQRP is to present the results of MMPR at a group level to the participating clinical departments. Based on these data, health care providers and researchers can develop a process that will encourage continued improvement of rehabilitation programs. The register includes descriptive variables of the patient's background, pain characteristics, and other symptoms such as depression and anxiety, function, activity/participation, and quality of life. Generally, the validated Swedish language versions of the instruments are used. At the assessment, it is possible to summarize (mainly in a graph) each patient's results from the first questionnaire. In a dialogue with the patient, this summary graph can be used to complement clinical support for diagnostics and to develop a rehabilitation plan for the patient. In the present study, data were used from one clinical department – Pain and Rehabilitation Centre at the University Hospital, Linköping, Sweden.Inwork), and number of days since in work (DaysnotWork) were selected from SQRP.Age (years), gender, employment  and for the previous seven days (Painint7d). The participants marked a 100-mm horizontal line between end points 0 (no pain) and 100 (worst imaginable pain). On a drawing with 36 anatomical predefined areas, the subject marked the anatomical areas where they have pain. The number of the above pre-defined anatomical regions associated with pain was calculated and labelled the Pain Region Index (PRI). The possible range was between 0 and 36. The duration of pain  and the duration of persistent pain  were also registered.Pain intensity was registered using a visual analogue scale (VAS) for current pain . The participants marked a 100-mm horizontal line between the end points 0 (no fatigue) and 100 (worst imaginable fatigue).The Hospital Anxiety and Depression Scale (HADS) is a short self-assessment questionnaire that measures anxiety and depression Life Satisfaction Questionnaire (LiSat-11) The Modified Somatic Perception Questionnaire (MSPQ), a 13-item self-report scale for patients with chronic pain or disabilities The West Haven-Yale Multidimensional Pain Inventory – (WHY) MPI – is a 61-item self-report questionnaire measuring psychosocial, cognitive, and behavioural effects of chronic pain Disability Rating Index (DRI) was mainly used to assess physical aspects of disability Ill-health was registered using a visual analogue scale (VAS). The participants marked a 100-mm horizontal line between the end points 0  and 100 .All statistics were performed using the statistical package IBM SPSS Statistics (version 20.0) and SIMCA-P+ ; in all tests, a probability of <0.05 (two-tailed) was accepted as the criteria for significance. In tables and text, the mean value ± one standard deviation (± 1SD) of the investigated variables is given.Principal component analysis (PCA) using SIMCA-P+ was used to extract and display systematic variation in a data matrix. All variables were log transformed before the statistical analysis. A cross validation technique was used to identify nontrivial components (p). Variables loading on the same component were correlated and variables with high loadings but with opposing signs were negatively correlated. Variables with high absolute loadings which had 95% jack-knife uncertainty confidence interval non equal to zero were considered significant. Hence, the most important variables were those with high absolute loadings. Significant variables with high loadings (positive or negative) for the component under consideration are more important than variables with lower absolute loadings. The obtained components per definition are not correlated and are arranged in decreasing order with respect to explained variation. R2 describes the goodness of fit – the fraction of sum of squares of all the variables explained by a principal component 2 describes the goodness of prediction – the fraction of the total variation of the variables that can be predicted by a principal component using cross validation methods 2 (identifies strong outliers) and 2) distance to model in X-space (identifies moderate outliers).PLS  was used for the multivariate regression analyses p = 0.121). The descriptive data  of the different variables and instruments of the patient cohort is summarized in .The investigated cohort of patients with chronic pain was comprised of 30.9% men and 69.1% women. The proportion of the patients in work was very similar with respect to gender: 31.4% of the women and 33.9% of the men . The significant PCA identified four components . The first component (p1) was characterized by positive correlations between pain intensity, psychological strain , amount of symptoms (MSPQ), DRI, and ill-health. The first component was negatively correlated with Life control and the general activity-index of MPI and most of the items of the LISAT .–Based on the PCA presented above –4 and t2R = 0.37, Q2 = 0.37; According to the significant regression of DRI  pain intensity. For HAD-A, 30.7% had high values according to this variable. The corresponding figure for HAD-D was 27.1%. According to these values, 59.8% of the patients had dichotomizing normal (low) values as defined by the two subscales of HADS Table3 SD) of variables reflecting participation and health in 2R = 0.89; 2Q = 0.82)  for the subgroups by projecting down to the X-axis with respect to p1 . Moreover, having high on two variables out of three variables  is worse than having only one high variable  and small differences in t-values existed between SG2, SG7, and SG4.To investigate the clinical relevance of the identified eight subgroups (SG1-8), mean values (±1  = 0.82) Figure 5Major results of this study are listed below:Common symptoms in patients with chronic pain  showed great variability across subjects.With respect to the investigated aspects of participation and health, pain intensity showed stronger multivariate relationships than psychological symptoms.With respect to depressive and anxiety symptoms, 60% of the cohort of patients with chronic pain referred to a pain centre at a university hospital had normal values.With respect to participation and health, high depressive symptomatology had greater negative consequences than high anxiety.The fact that common symptoms in patients with chronic pain such as pain intensity, depression, and anxiety showed great variability across subjects  indicates that these symptoms carry important information concerning the situation of the patients. Patients with chronic pain describe wide consequences of their pain condition and several studies have reported that clinically important outcomes from the patient's perspective are in fact symptoms such as pain intensity, emotional well-being, and fatigue The regressions of DRI and ill-health also identified interesting results concerning the relative importance of the different symptoms. In both these regressions, pain intensity variables were more important than the psychological symptoms such as depression and anxiety Table2.The four most important regressors of DRI were also the most important regressors in the regression of ill-health. In this regression, however, depression (HAD-D) and affective distress (MPI-affective distress) also were significant. Hence the relative importance of these psychological factors was stronger in the regression of ill-health than in the DRI, but still less important than pain intensity.Fatigue was the fourth most important regressor in both regressions Table2.Another observation from the two regressions was that both duration of pain and duration of persistent pain were not significant regressors of DRI and ill-health. Similar results were also obtained in our previous study of patients with chronic pain 2 and Q2) of DRI and ill-health, we can identify a number of factors that could have contributed to higher R2. For example, studies have pointed out that other symptoms and aspects – e.g., catastrophizing Both regressions Table2 Depression and anxiety contribute, in the acute and sub-acute phases, to the development of chronic pain As clearly shown in the present study, the presence of both depression and anxiety (SG8) was associated with a very bad situation compared to the other subgroups Table4.The concept of subgrouping chronic pain patients is not new, but various variables have been used in the subgroupings as noted in the introduction –When choosing variables for subgrouping based on the PCA Figure 1Subgrouping can have different aims, but from a treatment and rehabilitation perspective, the validation of the chronic pain patient's subgroups needs to be done in prospective intervention studies. The question arises whether SG8 and the other subgroups with high depression need both treatment for their pain and depression instead of treating pain and expecting secondary positive consequences for depression Classical statistical methods can quantify the level of individual factors but disregard interrelationships between different factors and thereby ignore system-wide aspects An obvious strength of the present study is that it represents the consecutive flow of patients at a multidisciplinary pain centre and it had a high participation rate (88%). Moreover, the patients in this study were recruited from a clinical department that specializes in managing severe chronic pain conditions. Because this recruitment was associated with a cohort of patients with severe pain and long pain duration, it is difficult to generalize the results of the present study to subjects in the population with less severe pain Common symptoms in chronic pain conditions, such as pain intensity and depressive and anxiety symptoms, carry important information that can be used to identify clinically relevant subgroups. Simply assessing the intensity of different symptoms without considering the actual data in clinical practice appears to be both a waste of time and information. Future prospective studies should investigate the relevance of the identified subgroups with respect to treatment outcomes and compare this method with other methods of subgrouping.Pain intensity and depressive and anxiety symptoms in patients with chronic pain carry important information that can be used to identify clinically relevant subgroups.