Based on recent success of intra-articular (IA) Botulinum neurotoxin type A  in patients with osteoarthritis, we examined if repeat IA-BoNT/A is an effective antinociceptive in patients with refractory arthroplasty pain.11 patients with refractory chronic arthroplasty joint pain without any evidence of infection or prosthesis loosening were referred by orthopedic surgeons. After discussion of off-label use, each patient underwent IA injection of BoNT/A, repeated based on return of pain on numeric rating scale (NRS) and functional limitation on composite validated scales, Western Ontario McMaster Osteoarthritis index (WOMAC) or Shoulder Pain and Disability (SPADI).11 patients  with 14 painful arthroplasty joints  underwent ≥1 IA-BoNT/A injections  with doses ranging 100–300 units. Mean age was 68 years  and follow-up ranged 1–28 months. Clinically meaningful reduction of 2-units in pain severity and really meaningful reduction in pain severity (50% reduction) were reported by 6/11 patients (6/13 joints) and 3/11 patients (3/13 joints), respectively, 1 month after the first IA-BoNT/A (100-units each). Significant improvements were noted in composite functional scales (WOMAC/SPADI). Pain relief was sustained at 3–4 month follow-up and was reproducible in those who received repeat injections. No significant adverse events were seen in any patients.A single intra-articular injection of BoNT/A improved pain and function in patients with chronic, refractory painful knee or shoulder arthroplasty, which sustained with repeat injections. Patients who were refractory to the first injection, did not respond to subsequent injections of higher dose of IA-BoNT/A. Total knee arthroplasty (TKA) is the commonest of all total Joint arthroplasty (TJA), with an annual volume of 300,000 in the U.S. in 2005 which is projected to increase 6-fold to 3.48 million/year by 2030 . Total sBotulinum neurotoxin type A (BoNT/A) is a neurotoxin approved for the treatment of several conditions including wrinkles, cervical dystonia etc. It can modulate the release of neuropeptides such as Substance P (SP) and calcitonin gene-related protein (CGRP) and inhibit neurogenic inflammation,  which liUsing a retrospective study design, we reviewed prospectively collected clinical pain and function data on a consecutive sample of 11 patients with 14 painful TJA joints. The study was approved by the Minneapolis Veterans Affairs Medical Center’s Institutional Review Board. All patients were referred to the rheumatology clinic by orthopedic surgeons for potential novel therapies including IA-BoNT/A injection. The referring orthopedic surgeons worked up these patients with moderate to severe refractory prosthetic joint pain and ruled out implant infection, loosening or any surgically explainable cause of pain and determined that there were no surgically correctable causes for refractory arthroplasty pain. All patients had failed treatment with oral medications and were deemed as not candidates for revision arthroplasty. We provided a detailed explanation of “off label” use of IA-BoNT/A injection (not approved by the U.S. Food and Drug Administration for intra-articular use), known potential adverse effects as well as the potential risks of IA injection into a prosthetic joint. All subjects gave written informed consent for intraarticular injection and received a single IA-BoNT/A of 100 units  reconstituted in 5 ml of normal saline initially. Patients requested and received reinjection with IA-BoNT/A  when the pain in the index joint returned to near pre-injection levels. If a patient had responded well to 100 units IA-BoNT/A, they received the subsequent injection with the same dose. If they had had no response, the dose was increased for the next injection. An accurate intra-articular needle placement was confirmed by aspiration of joint fluid in each case before injection. Patients were requested to return to the clinic every 1–3 months for a clinical follow-up. There was no placebo control and patients or providers were not blinded.A standardized chart abstraction form was used to extract prospectively collected demographic data, treatments, pain severity, function assessment with Western Ontario McMaster Osteoarthritis index (WOMAC), Shoulder Pain and Disability (SPADI) and Timed Stands Test (TST), standard manual joint examination and possible adverse effects. WOMAC and TST were selected since they provide subjective and objective assessments of lower extremity function and pain; SPADI provides pain and function assessment for the shoulder. Pain severity was assessed on a 0–10 numeric rating scale (NRS) where 0 is ‘no pain’ and 10 is ‘worst possible pain’. Function was assessed by SPADI total score for shoulder ; 50% chaNo funding was obtained for this study. Data are available for sharing with approvals from the appropriate institutions, Ethics committees and Privacy Protection for data transfer.Eleven patients  with 14 chronically painful  arthroplasty joints  underwent one or more IA-BoNT/A injections with doses ranging 100–300 units. The first injections were with 100 units IA-BoNT/A each. Repeat injections were 100–300 units. Eight joints were injected once (100 units BOTOX® each), one joint injected twice (100 units BOTOX® twice), five joints injected thrice . Mean age was 68 years , 90% were men and follow-up ranged 1–28 months .Mean NRS daytime pain decreased significantly p<0.001;  from 7.0Four patients with six joints requested and received the second IA-BoNT/A injection (100 units each in two joints and 200 units each in four joints), which was associated with significant mean daytime NRS pain reduction (p=0.044), similar to the first injection . This coThis study provides evidence for efficacy of IA-BoNT/A in patients with refractory, chronically painful TJA not amenable to medical/surgical treatment, a difficult clinical problem. Our study provides a much longer follow-up compared to the 2-month primary outcome assessment in a randomized controlled trial. This study is the first time to provide the evidence related to the efficacy of repeat IA BoNT-A injections for the improvement of pain and function in patients with refractory, chronically painful TJA . This obThese patients were deemed as not candidates for revision surgery by the referring orthopedic surgeons. While one needs to be very cautious regarding injecting a sterile prosthetic joint due to the potential risk of septic arthritis, in absence of an effective non-surgical treatment option, many of these patients seek and receive revision surgery  for their refractory painful TJA, which clearly have higher infection risk and morbidity compared to an intraarticular injection. The beneficial effect of the first IA-BoNT/A injection was reproducible with repeat injections in several patients, without any evidence of loss of magnitude or duration of pain relief. BoNT has not been approved by the U.S. Food and Drug Administration for joint pain. Therefore, this constitutes an “off-label” use and should be considered only after a full understanding of risks/benefits by the patients and care providers. To our knowledge, this is one of the largest case series of IA therapy in patients with chronic, refractory, painful TJA.Two patients with 4 painful TKAs did not respond to any dose of IA-BoNT/A, despite escalation of dose and three injections. That not all refractory painful TKAs will respond to IA-BoNT/A is an important observation. Most patients responded very well to IA-BoNT/A. This implies that among patients with chronic refractory painful TKA, most responded to 100 units initial dose of IA-BoNT/A, and that there was not a dose-threshold for antinociceptive effect. Due to a small number of patients, we were unable to determine as to what factors can predict the probability of response/non-response. No falls, neurological deficits, septic arthritis or systemic side effects of BoNT/A were noted in our small study.Botulinum toxin A (BoNT/A) injections have an independent antinociceptive effect , in addiOur retrospective study has several limitations. Due to the lack of blinding and placebo, results may be biased by patient expectation and patient/observer bias. However, all patients had failed 1–2 surgeries and multiple pain medications for persistent post-arthroplasty index joint pain. Pain assessments were done at clinic follow-up, which led to range of follow-up periods for this study, rather than fixed time-points in large randomized trials. The length of follow-up varied, since some patients did not return for follow-up after 6–12 months and several requested reinjections at 3–6 months when the effect of initial injection wore off. An exception was a patient who reported 100% pain relief up to 28 months after single injections in both index arthroplasty joints. These results may only be applicable to patients with chronic, unexplained, refractory prosthetic joint pain without infection, fracture or loosening/wear. We included several different doses and heterogeneous patient populations (previous responders in whom effect wore off and non-responders) for the second and third injections that likely impacted the results, therefore these results should be interpreted with caution. A small number of patients in our study did not allow us to observe any differences in patient characteristics between responders and non-responders. Our sample was predominantly men therefore these results may not be generalizable to women with painful, refractory TKA.In conclusion, this small study adds to the growing evidence supporting the anti-nociceptive effects of intra-articular botulinum toxin and its potential benefit in patients with refractory, chronic post-prosthetic joint pain. This is a challenging clinical problem for reconstructive orthopaedic surgeons. Our study was limited in generalizability, had small numbers, was retrospective and unblinded. Nevertheless, it showed evidence of potential benefit in pain relief and functional improvement in patients with chronic unresponsive post-prosthetic joint pain. Thus, it intra-articular botulinum toxin might be a potential clinical tool for providers who take care of such patients. We recommend further investigations be undertaken to further validate our findings and more closely assess the potential benefits and harms of this treatment.


The pain in Fibromyalgia (FM) is difficult to treat and functional mobility seems to be an important comorbidity in these patients that could evolve into a disability. In this study we wanted to investigate the analgesic effects of music in FM pain. Twenty-two FM patients were passively exposed to (1) self-chosen, relaxing, pleasant music, and to (2) a control auditory condition (pink noise). They rated pain and performed the “timed-up & go task (TUG)” to measure functional mobility after each auditory condition. Listening to relaxing, pleasant, self-chosen music reduced pain and increased functional mobility significantly in our FM patients. The music-induced analgesia was significantly correlated with the TUG scores; thereby suggesting that the reduction in pain unpleasantness increased functional mobility. Notably, this mobility improvement was obtained with music played prior to the motor task (not during), therefore the effect cannot be explained merely by motor entrainment to a fast rhythm. Cognitive and emotional mechanisms seem to be central to music-induced analgesia. Our findings encourage the use of music as a treatment adjuvant to reduce chronic pain in FM and increase functional mobility thereby reducing the risk of disability. Listening to music reduces acute and chronic pain  is a chronic pain syndrome that is characterized by diffuse multifocal pain accompanied by fatigue, sleep disturbances, depression, cognitive, and memory issues, and alterations in sensory processing such as touch, audition, and vision  to determine if slow-paced, self-chosen, highly pleasant music, regardless of the style reduces pain in FM; (2) to test if this music increases functional mobility in FM patients; (3) to determine if changes in functional mobility are related to pain and analgesia. We hypothesized that self-chosen music would reduce generalized pain in FM patients and consequentially increase their functional mobility.Twenty-two patients (21f/1m) diagnosed with FM, with an age between 22 and 70 years (median = 50) participated in the study. Prior to their participation the patients were interviewed about their clinical history, FM history, and medication. The patients were included in the study if they fulfilled the following criteria: (1) Diagnosis by a trained rheumatologist according to the American College of Rheumatology 1990 criteria for more than 1 year   and pain unpleasantness (PU) . Peak normalization is an automated process in which the software scans the entire signal to find the loudest peak, and then adjusts each sample to a specific level. It is used to ensure that the signal peaks at the loudest level allowed in a digital system and does not cause clipping in the sound system. To fit the music in 10 min, the patients had to listen to three songs, with the last one usually being cut short. The patients listened to the stimuli using Sennheiser HD 205 headphones with passive attenuation of ambient noise . To avoid any type of cognitive or analgesic “crossing” between auditory stimuli, a washout condition was used that consisted of watching and listening to a documentary chosen randomly by the experimenter from a pool of four different themes. We let the participant choose in order for them to actively attend to the video. The documentaries were about the history of the Mayans, the Aztecs, Egypt, and about Bill Gates. The washout condition lasted 10 min. The auditory stimuli and washout were presented using an Apple MacBook Pro laptop computer using the open-source software VLC Media Player (http://www.videolan.org).Patients were presented with two auditory backgrounds: a control (pink noise) and a musical piece. The music piece was semi self-chosen music (see Procedure) that was highly pleasant and slower than 120 beats-per-minute Table . The conThe patients were recruited from a FM help group, where author JIRR gave a talk about new scientific findings in FM pain to the patients, specifically about cannabinoids. Author EAGV then announced about the scientific study of FM, without being specific as to the tasks involved and the main objective . The volunteering patients where then added to a list for a following phone interview. In the phone interview the patients were screened for inclusion and exclusion criteria mentioned in the sub-section “Participants.” Then, we asked the patients for their favorite songs, musician, or band, taking into consideration that we wanted the songs to be pleasant and relaxing. The patients were asked for the names of at least three songs they wanted to listen to. We pre-screened the songs selected by the patients in order to ensure all songs in the experiment would have low beats-per-minute. The music chosen varied in cultural background and genre ranging from classical music to folk music; however, we chose music that had to ensure relaxation based on the patient's songs suggestions  and PU . This means the patients reported feeling less pain after the music rather than after the control auditory stimulus. Furthermore, the patients were significantly faster after the Music condition in the TUG task , but not after the Control condition.The patients demographic and questionnaire results are shown in Table r = 0.63, p = 0.007) suggesting that when the patients reported less PU, they were also faster at the TUG task for functional mobility  and ΔPU . This means that the older the patient the higher analgesic effect reported. Interestingly, there was no correlation between “age” and control ΔPI nor ΔPU.The correlation analysis showed significant positive correlation only between the music ΔPU and ΔTUG  in the amount of pain the patients report, (2) in the co-morbidities such as depressive symptoms and (3) in the medication used. This could introduce noise in the data that could inflate the type II error . Nevertheless, in our study the analgesic effect of music seems to be robust enough to overcome this. Most of the music in our study included lyrics, so it is not possible to separate the effect of the lyrics from the musical score. However, this was not the purpose of our study (although, see Brattico et al., In this study we found that listening to music that is relaxing, highly pleasant, familiar, and self-chosen, reduced pain and increase functional mobility in fibromyalgia patients. We also found that the improvement in functional mobility was closely related to music-induced analgesia, especially in the affective dimension of the pain. Therefore, we suggest that music reduces pain in fibromyalgia by means of cognitive and emotional mechanisms and that this analgesic effect is strong enough to increase their functional mobility. We suggest that it is important to exploit the features of the music known to produce the strongest analgesic effect when it is used as an adjuvant for pain therapy.The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.


Evidence from animal and human studies imply the amygdala as the most critical structure involved in processing of fear-relevant stimuli. In phobias, the amygdala seems to play a crucial role in the pathogenesis and maintenance of the disorder. However, the neuropathology of specific phobias remains poorly understood. In the present study, we investigated whether patients with spider phobia show altered amygdala volumes as compared to healthy control subjects.Twenty female patients with spider phobia and twenty age-matched healthy female controls underwent magnetic resonance imaging to investigate amygdala volumes. The amygdalae were segmented using an automatic, model-based segmentation tool (FSL FIRST). Differences in amygdala volume were investigated by multivariate analysis of covariance with group as between-subject factor and left and right amygdala as dependent factors. The relation between amygdala volume and clinical features such as symptom severity, disgust sensitivity, trait anxiety and duration of illness was investigated by Spearman correlation analysis.Spider phobic patients showed significantly smaller left amygdala volume than healthy controls. No significant difference in right amygdala volume was detected. Furthermore, the diminished amygdala size in patients was related to higher symptom severity, but not to higher disgust sensitivity or trait anxiety and was independent of age.In summary, the results reveal a relation between higher symptom severity and smaller left amygdala volume in patients with spider phobia. This relation was independent of other potential confounders such as the disgust sensitivity or trait anxiety. The findings suggest that greater spider phobic fear is associated with smaller left amygdala. However, the smaller left amygdala volume may either stand for a higher vulnerability to develop a phobic disorder or emerge as a consequence of the disorder. Specific phobias are characterized by automatic, exaggerated fear responses towards phobia-specific objects. ConvergTwenty female patients with a current diagnosis of spider phobia and twenty healthy female controls matched for age were included in the analysis. Subjects were recruited via advertisements. The data used for this report has been collected in a larger project investigating the effect of cortisol on the outcome of an exposure-based short-term group therapy for spider phobia. Because the study design included an exposure task and in order to minimize motion artifacts, only patients that could keep still while facing a picture of a spider were included in the magnetic resonance paradigm. Exclusion criteria for patients were the following: any axis I other than specific phobia for spiders, axis II disorders, the manifestation of acute or chronic medical condition, neurological diseases, current drug or alcohol abuse or any contraindication to magnetic resonance imaging  or confounding factors for structural brain studies . Healthy control subjects were excluded from the study if they met any of the following exclusion criteria: axis I-disorders (measured with the SCL-90-R), the manifestation of acute or chronic medical condition, neurological diseases, current drug or alcohol abuse or any contraindication to magnetic resonance imaging  or confounding factors for structural brain studies . Informed written consent was obtained from all participants after description of the study, which was approved by the ethics committee of the Canton of Bern, Switzerland (161/07) in accordance with the principles of the Declaration of Helsinki. WrittenPatients: Diagnoses for specific phobia for spider was based on the Diagnostic and Statistical Manual of Mental Disorders, fourth edition (DSM-IV). SpecifiControl subjects: SCL-90-R was used as short screening to exclude Axis-I disorders (such as anxiety disorders and depression) in the control subjects.All subjects filled out the German version of the Spider Phobia Questionnaire (SPQ) and a quMagnetic resonance imaging was performed on a 3 T Siemens Magnetom Trio Scanner  equipped with a standard radio-frequency head coil. For structural images, a high-resolution 3D T1-weighted imaging protocol  was usehttp://fsl.fmrib.ox.ac.uk/fsl/fslwiki/) was used= 6.39; p= 0.02; FigureF= 1.72; df= 36, p=0.20) and BMI . There was no significant difference of right AMV between patients and controls  and BMI . Correlations between left amygdala and the disgust score (FEE) or state anxiety (STAI trait/state) did not reach significance, nor were there any significant correlations between right AMV and clinical scores within the whole sample. Within the phobic sample, trait anxiety did not correlate with AMV. Thus, differences in AMV did not appear to be due to age or BMI or clinical features of the participants.Multifactorial ANCOVA of AMV, adjusted for ICV, showed approximately 13% smaller AMV in patients on the left than in controls, resulting in a significant between group effect for left AMV  and trait-anxiety (STAI-trait). Whereas the control subjects were only screened for possible axis I-disorders (SCL-90-R) which implied exclusion of the study. Additionally, the sample size was modest and should be extended. However, the patient group can be considered to be homogenous, as patients did not suffer from any other axis I disorders at the time of assessment. Hence, future investigations should include comparisons of amygdala morphology in various types and degrees of phobic disorders for a better pathophysiological distinction. Longitudinal and pre-post treatment studies should clarify the meaning of the observed amygdala differences over time.Still, the reasons for volumetric differences are so far largely unclear. Two possible interpretations might be offered: First, smaller left AMV might be a vulnerability factor for the development of spider phobia. The second interpretation relates to experience or exposure-related structural modifications within the amygdala. Whether the observed atrophy of the amygdala in mood and anxiety disorders is progressive and already present at time of disease onset or develops as a result of damage secondary to higher amygdala activity is a matter of debate,46.AMV: Amygdala volume; ANCOVA: Analysis of covariance; BMI: Body mass index; EHI: Edinburgh handedness inventory; FEE: Questionnaire for the assessment of disgust sensitivity; FOV: Field of view; ICV: Intracranial volume; SD: Standard deviation; SP: Spider phobic patients; SKID-II: Structured clinical interview for DSM-IV Axis II disorders; SPQ: Spider phobia questionnaire; STAI: State-trait anxiety inventory.The authors declare that they have no competing interests.MF participated in the design of the study, carried out the measurements, performed the statistical analysis and drafted the manuscript. AF carried out the sequence alignment and revised the manuscript critically. HH participated in the diagnostic interview and revised the manuscript critically. TD revised the manuscript critically. WS participated in the diagnostic interviews. DQ made the conception and design of the study and revised the manuscript critically. LS participated in the design of the study and revised the manuscript. All authors read and approved the final manuscript.The pre-publication history for this paper can be accessed here:http://www.biomedcentral.com/1471-244X/13/70/prepub


The benzodiazepines are used primarily for anxiolysis, amnesia and sedation. However, recent investigations have shown that some forms of this group of drugs have also direct effect on pain. This study aims to determine the effect of midazolam in reducing the severity of pain in women scheduled for elective cesarean section.In a prospective, double blind randomized controlled trial, two groups parallel study, was conducted in Imam Reza/Moatazedi Hospital, an affiliate of Kermanshah University of Medical Sciences. Parturient women who met study inclusion criteria were consecutively assigned into either experimental (n=62) or control groups (n=62). Women in the experimental group received bupivacaine (10 mg) plus intrathecal midazolam (2 mg/ml) (BM) and those in the control group received bupivacaine plus normal saline (BNS). The outcome pain severity was measured by Verbal Numerical Rating Scale.In comparison with the BNS group, mothers in the BM group reported a significant relief in pain (15 min and 120 min) after the surgery. There were no significant differences between the groups regarding the intensity of pain 5, 30, 60 and 240 min after the surgery. The average time until the first dose of additional analgesic, per mother’s request was 142.18±55.19 min in the BNS vs 178.06±77.33 min in the BM group.Combination of bupivacaine plus intrathecal midazolam was an effective anesthetic technique to provide improvement in pain. The onset of sedation was faster in the BM group compared with the BNS group. The duration of effective analgesia, and the time for regression of sensory analgesia was the same in both groups in our study. However, incidence of nausea and vomiting was higher in the experimental group. The benzodiazepines are used primarily for anxiolysis, amnesia and sedation. However,The long-term administration of intrathecal midazolam infused with clonidine has also provided promising evidences of almost immediate and complete pain relief in four patients with refractory chronic benign pain. Even with continuous use, these patients did not show any sign of building tolerance against the drug, no toxic effect on nerve roots were reported and other side-effects were minimal.As indicated in the aforementioned studies, while intrathecal midazolam has been used for the management of different types of pains in different type of patients, but its analgesic effect in women undergoing cesarean section is less documented. Twenty years after the introduction of intrathecal use of midazolam, providing relief from pain after cesarean section delivery with fewer side effects remains challenging for anesthesiologists.This study was an attempt to investigate the analgesic effect of intrathecal midazolam using a double blind randomized study of 124 pregnant women scheduled for elective cesarean section. The objective of this study was to determine the effect of midazolam in reducing the severity of pain in women scheduled with cesarean section. The underlying hypothesis was that intrathecal injection of midazolam interrupted the spinal cord pathways taken by pain afferents.This was a prospective, randomized double blind, two groups parallel study conducted in Imam Reza/Moatazedi Hospital, an affiliate of Kermanshah University of Medical Sciences. Pregnant women, 18-45 years of age with ASA I and II who were scheduled for elective cesarean section were screened for the study eligibility criteria.Prior to screening, the potential participants for eligibility, study coordinator explained details of the research protocol and gave them an ample amount of time to ask questions from the coordinator and/or physicians who were involved in the trial. Subsequently, eligible parturients signed the informed consent. The principle of the study protocol was approved by the Ethic Committee of Kermanshah University of Medical Sciences.Parturient women were included in the study if they met the following criteria: 1) Age between 18-45 years, 2) Had no severe spinal lesion, 3) Had no sign of abscess or infection of skin and soft tissue in the location of needle insertion, 4) Did not report severe anxiety and restlessness, 5) Had no sign of lesion in the central nervous system; 6) Did not present peripheral nerve lesion and 7) Did not screen positive for presence of significant mental disorders or drug abuse, and agreed to sign a written informed consent. Study sample, therefore, included 124 consented pregnant women aged 18-45 years who met all the study inclusion criteria.Parturient women were consecutively assigned into either experimental (n=62) or control groups (n=62). Both the investigators and the subjects were blinded to the randomization, using numbered unlabled 5 ml syringe containing study’s analgesic medication. Before induction of epidural anesthesia, all parturients received an infusion of lactated ringer’s solution (10 ml/kg). Standard monitoring devices including electrocardiogram, finger tip pulse oximeter, and non invasive blood pressure (NIBP) were used to measure the hemodynamic variables. Women in the experimental group received bupivacaine (12.5 mg/2.5 ml) plus intrathecal preservative-free midazolam (2.0 mg/ml) (BM) and those in the control group received bupivacaine (12.5 mg/2.5 ml) plus normal saline (1 ml) (BNS). Midazolam, at a concentration of 5 mg/ml formulations was diluted in 0.9% sodium chloride till the solution reached 2 mg/ml. Subarachnoid injection was performed, while the parturient was in the right lateral decubitus position. Injection was administered with a 24-gague Quincke spinal disposable needle at the L3-4 or L4-5 intervertebral space. Immediately after the subarachnoid injection, parturient was turned supine and her head was rested on a pillow. The time to successful onset and the levels of anesthesia were determined and recorded. Surgery was performed when sensory block at or above T6 was determined. Oxygen was administered routinely by face mask at 6 liter min-1 until the end of the operation. The time of the surgery, time of delivery and termination of the surgery were recorded as well.Vital sign parameters included blood pressure, pulse rate, respiratory rate, and pulse oximetry that were recorded at 5, 10, 20, 30, 45, 60, 120, and 240 min. Incidence and frequency of complications including nausea, vomiting, shivering, and itching, as well as their clinical managements that were recorded and monitored intra-operatively and postoperatively. Time to regression of sensation by 2 dermatomes as well as time patient reported complete recovery from anesthesia and mother’s motor function was assessed and registered postoperatively. Mothers’ level of sedation/alertness was subjectively assessed using the Observer Assessment of Alertness/Sedation (OAA/S) by the study anesthesiologist who rated mother’s responsiveness to verbal stimuli (i.e. repeating her own name) on a scale of 1=unresponsive to 5=alert. This was also recorded at 5, 15, 30, 60, 120, and 240 min, postoperatively.Severity of pain was measured by Verbal Numerical Rating Scale (VNRS). Mothers were asked to rate their pain from a scale of 0=no pain to 10=worse pain possible. Pain scores were recorded at 5, 15, 30, 60, 120, and 240 min, postoperatively. The newborn condition was assessed by the APGAR scores in the 1st and 5th minute of delivery.The study data is presented as mean±SD. Independent t-test (for quantitative data) and Mann-Whitney U test  were used to determine differences between the experimental and control group means. The level of significance was established at p<0.05. All the statistical analyses were performed using SPSS software .One hundred and twenty four women ages 18 to 45 years (mean=32 years) who were scheduled for elective cesarean section were enrolled. There were no significant differences between the two groups prior to the surgery with regard to mean age, height, weight, and gestational age. Anesthesia was achieved in 5.36±1.908 min in the control group and in 3.64±1.856 min in the experimental group and the difference between the two groups was significant (p=<0.001). The duration of analgesia in control group (BNS) was 107.77±43.273 vs 115.71±61.36 min in the experimental group (BM) (p>0.05).In compare with the BNS group, mothers in the BM group reported better relief in pain  after the surgery. Although, there were no statistically significant differences between the groups regarding the intensity of pain 5, 30, 60, 240 min after the surgery . The aveThis study showed that intrathecal midazolam produced a highly significant postoperative pain relief for the experimental (BM) 15 and 120 min groups. This finding was supported by previous studies. Tucker et al. intratheFindings from human studies also pointed to the analgesic effect of intrathecal midazolam. In one study, intrathecal administration of midazolam (0.3-2 mg dissolved in 3 ml of 5% dextrose) in nine patients with acute pain reduced post-operative somatic pains but not visceral pain. In a proThe mechanism that leads to antinoception effect of midazolam has been the subject of debates among various investigators. Findings from animal studies  suggested that midazolam exerted its effect at the neural level by reducing excitatory synaptic transmission i.e., acting on the gamma aminobutyric acid type A/benzodiazepine receptor in interneurons, leading to a decrease in the excitability of spinal dorsal horn neurons.30]31] [31] 30][ [31] 30]Our study showed that intrathecal administration of midazolam did not affect mother’s heart rate, blood pressure, or incidence of hypotension, itching, trembling, and need for extra emergency treatment. Also the condition of the newborns, evaluated by AGPAR score, was good in both groups. Similar results have been reported by others.12]19][19]12][1[19]12]38] [38] 37][ [38] 37]Our findings are limited since we were not able to evaluate the dose-response relationship of intrathecal midazolam. Further studies should be conducted to evaluate different doses of intrathecal midazolam on pain response among women undergoing cesarean section. Also, appropriate follow-up with the mothers are need to evaluate symptoms or adverse effects that may persist beyond expected recovery period.The present study demonstrated that combination of bupivacaine (10 mg) plus intrathecal midazolam (2 mg) was an effective anesthetic technique to provide improvement in pain. The onset of sedation was faster in the group that received bupivacaine plus intrathecal midazolam compared with those who received bupivacaine plus normal saline. The duration of effective analgesia and the time for regression of sensory analgesia was the same in both groups in our study. However, incidence of nausea and vomiting was higher in the experimental group.


Background. Recently, it has been proposed that fibromyalgia (FM), a chronic widespread pain syndrome, results from overactive endogenous excitatory pain mechanisms. Experimental studies using temporal summation paradigms have confirmed this hypothesis but have included small samples of patients, prompting our group to perform a large-scale study. Methods. Seventy-two female FM patients and 39 healthy females participated in the study. The temporal summation test consisted of a 2-minute continuous and constant heat pulse administered with a thermode on the participants' left forearm. Experimental temperature was set at a value individually predetermined to induce a 50/100 pain rating. Results. Relative to controls, FM patients had lower thermal pain thresholds and lower temporal summation of pain. However, 37 FM patients required experimental temperatures lower than the minimal temperature used in controls (45°C). Nevertheless, temporal summation was not increased in the other FM subgroup, relative to controls, despite equivalent experimental temperatures. Discussion. Our results suggest that temporal summation of pain is normal, rather than increased, in a large proportion of FM patients. Future studies on temporal summation in FM will need to be careful since some FM patients require abnormally low experimental temperatures that may confound results and make necessary to separate patients into subgroups. Fibromyalgia (FM) is defined by widespread chronic musculoskeletal pain , 2, desp The temporal summation paradigm is the experimental model the most frequently used in humans to study endogenous excitatory pain mechanisms . Temporal summation results in an amplification of pain perception following repeated or continuous administration of constant noxious stimuli , 5. Temp repetitive  noxious stimuli have repeatedly shown that temporal summation effects are more pronounced in FM patients, relative to healthy controls [n ≈ 15). Although such small-scale studies may have sufficient sample size to examine differences between FM patients and healthy controls, they are not suited to determine the rate of FM patients who have exaggerated windup. FM is a highly heterogeneous disorder, whose symptoms  vary considerably from one patient to another, and the pathophysiological processes underlying these symptoms may also vary considerably across subgroups of FM patients [ In human experimental settings, temporal summation is usually elicited using phasic repetitive pain stimuli administered at short interstimulus intervals (≥0.3 Hz) –10 or cocontrols –17, stropatients . In thispatients –21. Recepatients . Using tAmerican College of Rheumatology criteria [Université du Québec en Abitibi-Témiscamingue and Université de Sherbrooke approved the research protocol, and all participants gave their written, informed consent.Seventy-two women suffering from FM and 39 healthy women participated in this study aged between 18 and 65 years old. Patients were diagnosed with FM using Fibromyalgia Impact Questionnaire (FIQ) that measures the components of health  most affected by FM over the last week [The symptoms of FM were assessed using the French version of the self-administered ast week . The Freast week .In a pretest at the beginning of the session, thermal pain thresholds (TPTs) were measured by applying a thermode on the left forearm of participants. The Peltier thermode used  was a heating plate connected to a computer, which allowed a precise setting of experimental temperature. Subjects were advised that the thermode temperature would gradually increase from 32°C to 51°C (maximum) by a rate of 0.3°C per seconds until it reached their thermal pain tolerance. During the full thermal stimulation, pain intensity was continuously measured (at 1 Hz) using a computerized visual analog scale (COVAS), which ranged from 0 (no pain) to 100 (most intense pain tolerable). Subjects were also instructed to start displacing the COVAS' cursor when their sensations changed from heat to pain (TPTs). For each subject, the procedure was repeated twice to ensure the stability of measurement of the TPTs and the experimental temperature.The temporal summation test was completed after the pretest and consisted of a continuous heat pulse administered with a thermode for 2 minutes on the left forearm of participants. Experimental temperature reached a predetermined fixed value and remained constant during the 2-minute testing period (Time 0 to Time 120). It was set at a value corresponding to a temperature individually predetermined to induce a 50/100 pain rating during the 2 pretesting sessions used to determine the individual's TPT. That is, during the pretests, the experimenter noted the temperature associated with a 50/100 pain rating, as displayed on the Medoc software (laptop), for each subject. For the temporal summation stimulation, participants were not told that the temperature remains constant throughout testing, after reaching the individualized experimental temperature (Time 0). During the thermal temporal summation stimulation, pain intensity was also measured using the COVAS. Research in our laboratory has shown that pain perception scores increase through the 2 minutes of testing, most prominently during the last 15 seconds, even if the thermode temperature remains constant , 24, sugTime15–30 s  minus Mean COVAS scoreTime105–120 s) [For statistical purposes, we used 3 dependent variables, namely, (i) TPTs, (ii) experimental temperature, and (iii) temporal summation (Mean COVAS score5–120 s) . Analyser = 0.331; P = 0.005). Finally, none of the pain measures significantly differed between FM patients with and without antidepressants, as well as FM patients with and without anticonvulsants .Relative to healthy controls, FM patients (as a whole) had lower TPTs and lower experimental temperature . TemporaGiven that FM patients required lower experimental temperatures to achieve 50/100 pain ratings, and that it has been shown that low-intensity nociceptive stimuli elicit less (or even no) temporal summation than high-intensity stimuli in healthy subjects , we perfAs shown previously by our group and others, TPTs were lower in FM relative to HC , 26, 27,some chronic pain patients who are particularly hypersensitive to thermal pain.One possible explanation for the lack of increased or even lack of temporal summation of pain in FM is that we only included female patients in our study, whereas most previous studies on the topic included both male and female participants –17. HoweWe acknowledge that these methodological differences  between our procedure and the procedures used previously by other labs may explain the discrepancy of the results obtained in the FM < 45°C patients. However, the critical issue here is that these differences cannot rule out the main finding of our study, namely, that a large subgroup of FM patients do not have increased temporal summation of heat pain. Despite the fact that the experimental temperatures used in the FM ≥ 45°C patients and the controls were nearly identical , the FM ≥ 45°C subgroup did not display enhanced temporal summation of pain, relative to controls. That is, despite the use of sufficiently noxious stimuli (≥45°C) to induce temporal summation, pain amplification was normal in large proportion of FM patients (close to 50/100). This raises the possibility that previous studies were not able to demonstrate the existence of this large subgroup of FM patients because they had very small samples of patients, clearly underpowered to detect subgroup effects and not designed to do so. Moreover, using a fixed temperature rather than a temperature adjusted to pain perception may be problematic. For the same stimulation intensity, the perceived pain is significantly higher in FM patients. This augmented perception may be the sole explanation for the increased temporal summation. The augmentation of the healthy subjects' experimental temperatures to the perceived pain of FM patients may have further increased the level of temporal summation of heat pain observed in these subjects.Intriguingly, both FM subgroups did not differ in FIQ total and FIQ pain scores. Although the exact meaning of this result remains elusive, it may suggest that thermal pain hypersensitivity, as displayed by the FM < 45°C subgroup, is not a pathognomonic feature of FM, since the FM ≥ 45°C patients had significant levels of FM symptoms without having significantly reduced TPTs, relative to HC. Apart from the well-described mechanical allodynia, other pain mechanisms could be altered in these FM patients, including deficient endogenous pain inhibition, autonomic dysfunctions, enhanced appraisal of pain, and/or abnormal inflammatory responses . Furthern = 37) having very low TPTs, who all had experimental temperatures lower than 45°C, suggesting that this subgroup of FM patients was already sensitized to pain from the very start of thermal stimulations. Using fixed-temperature noxious stimuli to elicit temporal summation, it seems possible that we may have found this subgroup to have increased temporal summation of pain, relative to controls. If lower experimental temperatures are required to elicit 50/100 pain ratings in the FM < 45°C subgroup, it seems likely that fixed temperatures across groups would have been rated as more painful in the FM < 45°C patients, relative to controls. Head-to-head comparisons of temporal summation paradigms using repetitive versus continuous thermal stimuli as well as individualized and fixed temperatures will need to be performed in large samples of FM patients in order to verify this assumption.Overall, our results strikingly cast some doubt on the whole idea that endogenous excitatory pain mechanisms are overactive in the great majority of FM patients. However, it is important to be cautious when interpreting our results, since we cannot rule out that temporal summation may have emerged as significantly increased in the FM < 45°C subgroup if we had used another temporal summation procedure. Indeed, pain amplification has been repeatedly reported to be more pronounced in FM patients, relative to healthy controls, in seminal studies performed by other groups using fixed experimental temperatures –17. MoreAlthough the temporal summation results of the FM < 45°C subgroup must be taken cautiously for obvious methodological reasons, the lack of increased pain amplification in the subgroup of FM patients who received significant levels of tonic thermal noxious stimuli (≥45°C) has to be taken seriously. As such, this latter result may have decisive implications for the identification of FM subgroups and the characterization of underlying physiopathological processes. For instance, the finding of increased pain amplification in FM has prompted the hypothesis that glutamatergic disturbances may be involved in the physiopathology of FM . The res


Orofacial pain is one of the most common reasons for attendance at the dental clinic. The prevalence and the sources of orofacial pain vary from place to place and patients’ response to pain also differs. The aim of this study was to determine the prevalence and pattern of orofacial pain as well as the factors influencing patients’ response to orofacial pain among patients presenting for dental treatment in our center.Consecutive patients presenting with orofacial pain at the Dental Center, University of Port Harcourt Teaching Hospital during the one-year period of the study were recruited into the study. Patients’ demographic data were collected and recorded in special forms. Patients were later examined to confirm the specific cause of pain. This was also recorded. Data generated were analyzed using SPSS for Windows.Four hundred and forty-eight patients out of the 2,426 patients seen during the study period had orofacial pain, yielding a prevalence rate of 18.5%. There were 255 females and 193 males with most patients in the 17-27-year age group (49.1%). Lower jaw was commonly affected. Most patients presented after a period of at least one month, with severe and spontaneous pain. Most patients had drug therapy before presentation. Caries was the most common source of orofacial pain. Orofacial pain was not uncommon in our center and it accounted for about 20% of patients’ attendance in the center. Dental caries and periodontal diseases were the most common sources of orofacial pain while temporomandibu-lar joint pain and atypical facial pain were not common in our center. Young adults and females were most commonly affected. Facial pain occurs in the area under the orbitomental line, above the neck and in front of the ear, while oral pain occurs in the area of the oral cavity.2 Oral pain might arise from the tongue, oral mucosa, maxillary bone, mandibular bone and it might be dental in origin. Dental pain can arise from the tooth itself or from its supporting structures and can be acute or chronic with different characteristics.1Pain is an unpleasant subjective sensation connected with a potentially damaged tissue.4 Dental pain has been shown to influence patients in different ways.6 The most common influences are: consulting a dentist or doctor; avoiding certain foods; taking medications and disruption of sleep.3 Several behavioral influences, including reduced social contacts and inability to work, have also been reported.6Pain is a very frequent reason for patients’ attendance at the dental clinic and most of the pain is dental in origin.7 Some of these responses may include care seeking and self drug therapy.,10Patients’ response to pain perception has also been shown to vary and depend on several factors like sex, age, previous pain experience etc.4 However, there is none from this area of the country. The present study was thus designed with the aim of determining the prevalence and pattern of orofacial pain as well as the factors influencing patients’ response to orofacial pain among patients presenting for dental treatment in our center. This information is vital for designing oral health care preventive and management strategies.Several studies are available on the prevalence, pattern and impact of orofacial pain on the patients.This is a one-year hospital-based cross-sectional study of patients presenting with orofacial pain in the Dental Center of University of Port Harcourt Teaching Hospital, Port Harcourt, Nigeria. The hospital is a major referral center in the southern region of Nigeria. The Dental center of the hospital became a tertiary center about 5 years ago.Patients presenting with oral and/or facial pain during the period of the study were recruited after they had accepted to participate in the study. Consecutive pediatric and adult  patients with primary or referred orofacial pain were included. Patients whose presenting complaints and clinical findings did not include orofacial pain were excluded.The bio-data of the patients and the clinical history of the pain were collected and recorded in special forms. The data collected included: age, sex, marital status, occupation, the location of the pain, duration and characteristics of the pain. History of drug intake in response to the pain and associated symptoms such as headache and sleep disturbance were included. The patients were later examined to ascertain the specific causes of pain; these were also documented in the special forms. The history taking and examination were carried out by the same examiner for all the patients. Patients’ confidentiality and anonymity were preserved.Data were analyzed using SPSS for Windows, version 12.0 . Summary statistics  were performed to compare prevalence and pattern of presentation. Chi-square test was used to assess the relationship between pathology causing pain and the demographic variables (i.e. age and gender).A total of 2,426 patients were seen during the one-year period of the study, out of which 448 patients presented with orofacial pain. Thus, the prevalence of orofacial pain was 18.5%. Among the patients presenting with orofacial pain, 255 (56.9%) were females while the remaining 193 (43.1%) were males. Most of the patients presenting with orofacial pain were within the age range of 17-29 years (49.1%), followed by patients within the age range of 30-49 years (28.6%) . RegardiWith respect to the site of pain, lower jaw was the most common site with 218 (48.7%) cases, followed by the upper jaw with 169 (37.7%) cases; 61 (13.6%) cases were located on both the upper and lower jaws. Regarding the side of the face involved, 188 (42%) cases were on the left side and 172 (38.6%) were on the right side; the remaining 86 (19.2%) cases were on both sides.Most of the patients  presented to the clinic after they had experienced the pain for at least one month; 135 (30.1%) patients presented when the duration of the pain was between one week and a month while only 134 (29.9%) presented to the clinic within one week of experiencing the pain.Regarding the nature of pain, most  of the patients described it as stabbing; 161 (35.9%) stated that the pain they experienced was throbbing while 111 (28.4%) patients said that the pain had a dull nature. In 313 (69.9%) of the cases the pain was spontaneous while in 131 (29.2%) cases the pain was non-spontaneous. Two hundred and eighty-five (63.5%) of the patients had recurrent pain whereas in 157 (35.0%) cases the pain was persistent. Furthermore, 69 (15.4%) patients described their pain as very severe; 261 (58.1%) patients described it as severe; 79 (17.6%) described it as less severe, while the remaining 37 (8.3%) patients described it as not severe.Regarding drug therapy before presentation, 126 patients were on antibiotics, 33 (26.2%) of which had been prescribed by a qualified health professional. Similarly, 316 patients were on analgesics while only 56 (17.7%) of these had been prescribed. Regarding associated complaints, 277 (61.8%) patients had sleep disturbances while 250 (55.8%) had headaches.1With respect to the source of pain, dental caries involving the pulp was the most common source of orofacial pain , followed by periodontal diseases . Other sources of oral pain were tooth fracture , jaw fracture , oral ulcers , infected benign tumor , malignant tumor , temporomandibular joint pain  and atypical orofacial pain  (Table 10).Cross-tabulation of age and gender with the sources of pain showed that dental caries and periodontal diseases were more predominant within the 17-29-year age group and among the females. On the other hand, tooth fracture was more predominant within the 30-49-year age group and among the males. Finally, temporomandibular joint pain was more common among the males while atypical orofacial pain was more common among the females . However15 Nomura et al12 reported a prevalence of 33.7% among 11-12 year-old school children in Brazil; this is similar to a prevalence of 30.4% reported by Pau et al15 among 11-14 years old school children in Pakistan. In their study, Macfarlane el al13reported a lower prevalence of 23% among young adults aged 30-31 in Wales, United Kingdom. Among adults, Kikwilu et al3 reported a higher prevalence of 58.8% in Tanzania while McMillan et al11 in a study on Cantonese-speaking Chinese in Hong Kong reported a prevalence of 41.6%, which dropped to 24.2% when sensitivity was excluded. In a study on adults in Benin City Nigeria, Okunseri el al14 reported a prevalence of 34%. Our study investigated the prevalence of oral pain in a population of children and adults, and we reported a prevalence of 18.5% which is slightly higher but similar to 16.49% reported by Ivana et al1 in Zagreb among patients the same age.The prevalence of orofacial pain in our study was 18.5%. Prevalence of orofacial pain as reported by various researchers varies from place to place and among different age groups.,11 in their study reported no gender differences in pain prevalence among their patients. Similarly, in the earlier study conducted at Ile Ife by Fagade et al,9 no gender differences in pain perception were reported. However, in the present study and that of Ivana et al,1 female predominance was reported. It has been noted that females tend to have a lower threshold of pain and thus tend to seek medical attention much earlier than males who appear to tolerate pain better.8 This might be a reason for this observation. It has also been shown that, generally, females tends to seek medical help more promptly than their male counterparts,16 which might be another reason for the female predominance.McMillan et al17 The fact that the study was conducted near a tertiary student community could also be responsible for having a higher prevalence of dental pain among young adults. Our report, therefore, may not be a true reflection of what is obtained in the general population.In this study, most of the patients with oral pain were within the 17-29-year age bracket. This is not surprising because our study also revealed that caries with pulpal involvement is the most common source of oral pain within this age bracket and more female are affected. These findings are consistent with the earlier reports which suggest higher prevalence of dental caries among young adults and females.14 In their study in Burkina Faso, Varenne et al4 reported that 52.4% of clinic attendance was as a result of pain due to dental caries. Oginni et al17 in Ile Ife, Nigeria and van Palenstein et al18 in Tanzania reported that the most common reason for dental treatment demand in their center was dental caries and its sequelae. In addition, periodontal diseases are the second most frequent reason why patients present to the clinic on account of oral pain. This is consistent with the report of Varenne et al4 in Burkina Faso but differs in the respect that periodontal diseases are more frequent in males, while in this study they were more frequent in females. However, both studies agreed with the fact that dental traumas are more frequent in males.In addition, dental caries as a major cause of dental pain as reported in our study had earlier been reported by several authors from different parts of Africa.20Analysis of the relationship between the jaws and sides involved showed that oral pain was more commonly located on the lower jaw and on the left side of the face in most cases. The reason is not clear; however, the lower molars are more prone to caries, pericoronitis and perhaps referred pain from the heart.17 where patients delay their visit to the clinics and only come when the pain becomes unbearable. Most of our patients presented after a duration of at least one month. The reasons most patients gave for this attitude were: lack of funds;3 hoping that the pain would disappear on its own without treatment;1 they were on medications which on most time were self-prescribed.,1Regarding duration before presentation at the clinic, our experience is not different from reports from Nigeria and other parts of Africa,1 in their study where 87.42% of the patients had acute pain while 12.58% had chronic pain.Even though most patients postponed their visits to the clinic, most of them had pain which was stabbing and throbbing in nature; they also had spontaneous pain which they described as severe. These characteristics are more associated with acute dental pain rather than chronic pain, which is expected, based on the time they present to the clinic. This is explained by the fact that they visited the clinic when there was acute exacerbation of chronic dental pain. This observation is similar to the experience of Ivana et al3 The danger of this attitude cannot be overemphasized, especially when more sinister conditions like oral cancers are involved because the mortality and morbidity of most cancers depend on the stage at presentation; patients presenting earlier have a better chance of survival.2Most of the patients were on medication before presentation at the clinic. Most disturbing is the fact that about 75% of the patients on antibiotics and about 80% of the patients on analgesics had not been visited by any health professional. The impact of this behavior on emergence of resistant strains of microorganisms and development of irreversible pulpal damage cannot be overemphasized. This lifestyle further corroborates the earlier speculation that patients present late to the clinic because they are engaged in self treatment, hoping that the condition will disappear with time.Orofacial pain is not uncommon in our center and accounts for about a fifth of patients’ attendance in the center. Dental caries and periodontal diseases are the most common sources of orofacial pain while temporomandibular joint pain and atypical facial pain are not common in our center. Young adults within the 17-29-year age group are most commonly affected. Overall, females are affected and the mandible is more involved. Most patients present late to the clinic and only present when the pain becomes unbearable after engaging in self-medication.It is therefore important to educate patients in this region and other parts of Africa in the dangers associated with self-medication and late presentation for treatment. In addition, the government should address the issue of poverty in this region so that patients can better access available health care facilities because most delays in presentation are due to a lack of funds on behalf of the patients.


The causes of low back pain in China and Western countries are extremely different. We attempted to analyze the risk factors of low back pain in urban and rural patients under the dual economy with the simplified Chinese version of Roland-Morris disability questionnaire (SC-RMDQ) to demonstrate that SC-RMDQ could evaluate patients with low back pain arising from different causes.Roland-Morris disability questionnaire was translated into SCRMDQ according to international guidelines for questionnaire adaptation. In this study, causes of low back pain of 187 outpatients and inpatients  were analyzed. All patients underwent simplified Chinese version of Roland-Morris disability questionnaire (SC-RMDQ), simplified Chinese Oswestry disability index (SCODI) and visual analogue scale (VAS). Reliability was tested using reproducibility (intraclass coefficient of correlation – ICC) and internal consistency . Validity was tested using Pearson correlation analysis.The leading causes for low back pain were sedentariness (38.4%) and vibration (18.1%) in urban patients and waist bending (48.9%) and spraining (25%) in rural patients. Although causes of low back pain in the two groups of population were completely different, SCRMDQ had high internal consistency  and good reproducibility . SCRMDQ also showed significant correlation with Simplified Chinese version of Oswestry disability index (SCODI) and visual analogue scale (VAS) in rural areas  and in urban areas .Although causes of low back pain are completely different in rural and urban patients, SCRMDQ has a good reliability and validity, which is a reliable clinical method to evaluate disability of rural and urban patients. Low back pain is very common in clinical practice. More than 1/3 of patients visit orthopedic clinic due to low back pain Traditional Chinese version of RMDQ serves for evaluation of low back pain and is consistent in content continuity, reliability and validity with original English version, Italy version, Japanese version and Tunisia version According to guidelines for questionnaire adaptation by Beaton 204 outpatients with low back pain in Changhai Hospital of Shanghai and No. 89 Military Hospital of China met the criteria, but 8.3% refused to fill in the questionnaire. A total of 187 patients completed the questionnaire, including 94 men and 93 women with an average age of 41.3±13.3 year-old (range18–79). Inclusion criteria were as follows: (1) low back pain had lasted for above half a month; (2) low back pain originated from spine which had been proved by a spinal surgical specialist; (3) the patient received at least 6-year compulsory education and accurately understood the questionnaire. Patients within the half a year after the surgery, fracture, cancer-related pain or drug abuse were excluded. All patients filled in the simplified Chinese SCODI 2.1 To test reliability and consistency of simplified Chinese questionnaire in rural and urban population, internal consistency and test-retest reliability were assayed. Internal consistency was expressed as a Cronbach's α value All patients were scored with SCRMDQ, SCODI and VAS on visit. Then, SCRMDQ was compared respectively with SCODI and VAS and correlation analysis was performed for consistency. An excellent consistency suggested this questionnaire was effective.SASS 11.0 was used for statistical analysis. Data were expressed as the mean ± standard deviation (SD) and were analyzed using a Pearson correlation method with the level of significance p<0.05.A total of 187 patients, including 88 rural patients and 99 urban patients, completed the questionnaires. All patients came from two regions representing different economic development degrees: a general hospital in developed regions in eastern coast  and a primary hospital in an inland underdeveloped region . All patients suffered from pain in duration from 28.9 months to 61.0 months ranging in ages from 18 to 79 years . It was Multiple function questionnaires evaluating low back pain are currently available, including RMDQ, ODI and VAS. RMDQ is widely applied to evaluate the functions of patients with low back pain since it is simple and easy to fill in and be followed up with the telephone and letter. There have been multiple RMDQ versions in various languages globally. However, causes and degrees of low back pain are different in rural and urban areas of China due to life and work conditions. Reliability of SCRMDQ and suitability to the two groups of population has not been reported.Some studies illustrated that RMDQ had high reproducibility In this study, the Cronbach's α value of SCRMDQ is 0.883 in rural patients and 0.874 in urban patients, similar to recent studies, such as 0.94 for Tunisian version Although considerable epidemiological studies on low back pain have been conducted, the causes and pathogenesis are still unclear. Studies on low back pain are characterized by much subjective sensation, little objective positive test results and various and extensive risk factors. Therefore, animal model can not be copied completely. Epidemiologic studies are the major studying method. RMDQ is widely applied to understand the relationship between low back pain and its risk factors, to clarify pathogenesis of low back pain, and to investigate effective treatment and prevention methods. Now, multiple simplified versions are available such as RM-12, RM-16, RM-18, RM-23 and SIP-RM


Pain after total knee arthroplasty (TKA) is usually severe, and epidural analgesia or femoral nerve block has been considered to be an effective pain treatment. Recently, local infiltration analgesia (LIA) has become increasingly popular but the outcome of this method regarding the analgesic effect has not been fully evaluated. We compared local infiltration analgesia and femoral block with regard to analgesia and morphine demand during the first 24 h after TKA.40 patients undergoing TKA under spinal anesthesia were randomized to receive femoral nerve block (group F) or peri- and intraarticular infiltration analgesia (group LIA) with a mixture containing ropivacaine, ketorolac, and epinephrine. All patients had access to intravenous patient-controlled analgesia (PCA) with morphine postoperatively. Pain intensity at rest and upon movement was assessed on a numeric rating scale (0–10) on an hourly basis over 24 h if the patients were awake.The average pain at rest was marginally lower with LIA (1.6) than with femoral block (2.2). Total morphine consumption per kg was similar between the 2 groups. Ancillary analysis revealed that 1 of 20 patients in the LIA group reported a pain intensity of > 7 upon movement, as compared to 7 out of 19 in the femoral block group (p = 0.04).Both LIA and femoral block provide good analgesia after TKA. LIA may be considered to be superior to femoral block since it is cheaper and easier to perform. Pain after total knee arthroplasty (TKA) is usually severe and difficult to manage, and insufficient pain relief may delay recovery. The most effective pain treatment has traditionally been epidural analgesia or femoral nerve block  in combiAn alternative method for postoperative pain relief after TKA, which has attracted growing interest in recent years, is multimodal wound infiltration analgesic technique consisting of peri- and intraarticular infiltration of local anesthetics and NSAID in the knee (LIA) . This teOnly a few investigators have randomly compared LIA with other methods with proven analgesic effect, such as femoral block or epidural analgesia . ParvataFemoral block is known to be an effective pain treatment after TKA . We compThis randomized parallel clinical 1:1 trial was used to compare two protocols of postoperative pain relief after total knee arthroplasty. The inclusion criteria were as follows: patients with osteoarthritis or rheumatoid arthritis scheduled for primary unilateral elective total knee arthroplasty under spinal anesthesia, American Society of Anaesthesiologists (ASA) classification I–III, and more than 18 years old. Exclusion criteria were allergy or intolerance to one of the study drugs, renal insufficiency, epilepsy, language difficulty, mental illness, dementia, QT interval on ECG > 450 msec before start. After giving oral and written informed consent, 40 patients scheduled for primary unilateral total knee arthroplasty were randomly assigned to 2 groups of postoperative pain management immediately before the surgical procedure.The setting of this single-site academic trial was the orthopedics clinic at Karolinska University Hospital in Solna. The first patient was included on January 15, 2007 and the final patient was included on March 25, 2008.The randomization sequence was determined by mixing 40 tickets, 20 labeled “F” and 20 labeled “LIA” in sealed opaque envelopes, and drawing one envelope at a time. The anesthesiologist performing the spinal anesthesia and femoral block or supervising the LIA technique did not participate in the randomization procedure.Group F received a femoral block with ropivacaine  and group LIA received peri- and intraarticular infiltration with ropivacaine + ketorolac  and epinephrine .Before induction of spinal anesthesia, monitoring of oxygen saturation, blood pressure, and electrocardiogram (ECG) was started. Sedation was induced with midazolam , 1–2 mg intravenously. The level of spinal anesthesia was L2-L3 or L3-L4. Isobaric bupivacaine , 5 mg/mL at a volume of 3 mL, was injected with the patient lying with the operating side upwards.Before the start of the operation, all patients were sedated with midazolam or propofol , maintaining spontaneous ventilation. All patients received 2 g dicloxacillin intravenously before surgery. Antithrombotic therapy with low-molecular-weight heparin (LMWH), enoxaparinnatrium  40 mg, started the day before surgery and was given for at least 5 days. The TKA procedure was performed following application of a thigh tourniquet, which was inflated just before skin incision and released after wound closure.These patients received a femoral nerve block directly after spinal anesthesia. They were placed in the supine position. Under sterile conditions, the pulse of the femoral artery was identified, the needle  connected to a nerve stimulator  set up to deliver 1.2 mA was inserted cephalad, 45 degrees to skin and at the level of femoral crease, 1–1.5 cm lateral to the femoral artery pulse . The femThe connection of the nerve stimulator was changed from needle to catheter, and stimulation intensity was started at 1.2 mA until the desired motor response was obtained. Thereafter, the intensity was reduced to 0.2–0.4 mA. The catheter was secured in place with transparent dressing. After negative blood aspiration, 30 mL ropivacaine (2 mg/mL) was injected followed by 15 mL of the same concentration every 4 hours for 24 h . All patients had a urinary bladder catheter, inserted after spinal anesthesia and removed on the day after surgery. Group F received ketorolac (10 mg intravenously) in the post-anesthetic care unit, and again after 8 h and 16 h. The total dose of ketorolac was 30 mg.These patients received peri- and intraarticular infiltration of a solution containing 150 mL ropivacaine (2 mg/mL), 1 ml ketorolac (30 mg/mL), and 5 ml epinephrine (0.1 mg/mL). This solution was prepared by the operation nurse before the start of the surgical procedure. The solution was given sequentially: 30 mL was injected intracutaneously at the start of the operation, 80 mL was injected into the posterior part of the capsule, close to the incision line, in the vastus intermedius and lateralis and around the collateral ligaments before cementation, and 46 mL was instilled through an intraarticular catheter  inserted at the end of the surgical procedure. The total dose of ropivacaine during the first 24 h postoperatively was 300 mg and the total dose of ketorolac was 30 mg.In the recovery room, all patients were provided with a patient-controlled analgesia (PCA) morphine pump  programmed to give an intravenous bolus of morphine (2 mg/dose) on demand with a lock-out time of 6 min and maximum dose of 35 mg over 4 h. All patients were introduced to the PCA technique and encouraged to use it as often as needed. After 24 hours, PCA pump use was verified with a printout of all doses of morphine and their time of administration. In addition to PCA, all patients received paracetamol (1 g × 4), either orally or intravenously.All patients were informed preoperatively by the nurse about pain assessment using a numeric rating scale (NRS): 0 = no pain and 10 = worst imaginable pain, based on the visual analog scale. NRS score at rest or upon movement during the first 24 h was recorded on an hourly basis by the patients, if awake.ECG was performed preoperatively, 2 h after the end of surgery in the recovery room and 24 h postoperatively in the ward. All patients received postoperative physiotherapy, which started on the morning after operation.Power analysis was performed using average VAS/NRS score during 24 h as the primary variable. A previous study of patients undergoing knee arthroplasty treated with a femoral nerve block reported a mean visual analog scale score of 3.6 (SD 1.1) upon movement, at 24 h . We wantPrimary outcome. Differences in average pain intensity at rest and upon movement during the first 24 h after TKA were analyzed with the Mann-Whitney U-test. As we had 2 primary efficacy outcomes, a significance level of p < 0.02 was chosen for each analysis. No data were imputed for the primary outcome if the patient was asleep or unable to record NRS.Secondary outcome. Total morphine use via the intravenous PCA pump during the 24-h period in the 2 study arms were analyzed with the Mann-Whitney U-test. Descriptive statistics were used to describe the morphine dose per kg in each study arm.These were as follows. 1. Average pain intensity in 24 hours following imputation of missing data. Missing data was replaced by “0” if the patient was asleep. The most recent NRS score obtained was used to replace missing if pain rating was not provided due to other reasons. 2. The fraction of patients who reported a degree of pain intensity of < 5 at rest and during movement, i.e. mild pain intensity  in the 2We monitored indications of cardiac arrhythmias and incidence of reported adverse events.This trial (protocol no. 4773 KCR S2006-011) was conducted according to the Helsinki declaration and was approved by the regional ethics committee of the Karolinska Institute (EPN 151:2006/34610) and the Swedish Medical Product Agency (EudraCT 2006-002581-19). The trial was monitored by the Karolinska Trial Alliance. This trial was not registered in the FDA database of clinical trials.40 patients participated in this trial, which was conducted. 20 patients were randomized to LIA and 20 to femoral block. All patients completed the study. Data were analyzed according to strict intention-to-treat (sITT) analysis according to The average degree of pain intensity during the first postoperative day was low in both groups. The average degree of pain intensity at rest and upon movement was similar .The average total morphine use via the intravenous PCA pump during the first postoperative day was 10 mg higher in the femoral block group than in the LIA group, but this difference was not statistically significant . However1. Imputation of missing data by “0” if the patients was asleep, and using the most recent NRS score to replae missing data if pain rating was not provided due to other reasons resulted in a mean NRS at rest of 2.2 (95% CI: 1.4–3.1) in the femoral block group and of 1.5 (CI: 0.8–2.1) in the LIA group. The average pain score upon movement, following imputation of missing observations, was 2.2 (CI: 1.5–3.0) in the femoral block group and 2.1 (CI: 1.5–2.8) in the LIA group. 2. Incidence of NRS less than 5 throughout the 24-h observation period (probably acceptable pain relief) at rest and upon movement was twice as high in the LIA group than in the femoral block group . 3. The None of the patients had prolonged QT interval at the ECG 2 hours and 24 hours postoperatively. No adverse events were reported during the 24-h study period.Our data indicate that the 2 analgesic regimens gave similar quality of pain relief during the first 24 h. Some studies have compared LIA with other pain treatments after TKA, such as systemic analgesia and placebo, and have reported superior outcome with LIA regarding postoperative analgesia and opioid consumption. The positive results in those studies are not surprising, since the analgesic treatment in the control groups mainly consisted of less effective methods of postoperative pain treatment .Both femoral block and LIA resulted in low average pain intensity during the first postoperative day. The average degree of pain intensity at rest, but not upon movement, was slightly lower in the LIA group. This small difference is probably without clinical significance. The access to PCA-administered morphine until pain was acceptably low, NRS < 4, would be expected to result in a similar degree of pain relief. The total use of morphine per kg was similar in both groups, which indicates that the pain relief of both methods was comparable. Using ancillary analysis, we found that a pain intensity of greater than 7 on NRS with movement was less common in the LIA group, a difference that reached statistical significance. This result must be regarded as hypothesis generating, and should be confirmed by a separate study.We compared 2 routinely used methods that are both effective for postoperative pain relief in TKA. None of the patients in this study were given an analgesic other than intravenous morphine, administered through a PCA pump, and paracetamol (4 g in 24 h).Femoral block and LIA after TKA have been compared previously . HoweverThe tendency of lower efficacy with femoral block may be due to the fact that the posterior part of the knee is innervated by the sciatic nerve. Thus, a femoral block does not cover this area and supplementary treatment with systemic analgesics such as opioids and NSAIDs is needed. In our study, all the patients in the femoral group received ketorolac in a total dose of 30 mg intravenously during the first 24 h—the same amount as administered locally in the LIA group.One explanation as to why LIA is so effective might be that there is evidence for a clinically relevant peripheral analgesic action of intraarticular NSAIDs . The anaThe high quality of the femoral blocks in this study might be one explanation for the small difference in analgesic efficacy between the two methods. It is well known that the quality of a peripheral blockade might depend on the experience of the anesthesiologist, and all but 2 blocks were performed by an experienced anaesthesiologist (FA).Experience is also of importance for perioperative local infiltration. When we introduced the LIA method at our institution, we noticed that surgeons also have a learning curve in doing effective local infiltration. The more experienced the surgeon is, the more effective is the postoperative pain relief. This may also be due to less tissue trauma being produced by experienced surgeons.Open labeled studies have a disadvantage compared to blinded studies, due the interference of expectancy of the patient and the staff in interpretation of the outcome. The patients in group F received an initial femoral nerve block followed by bolus doses of ropivacaine every 4 h during the first 24 h, and not continuous infusion of local anesthetic, which might have been more effective due to a steady concentration of ropivacaine over time and probably better pain control. The randomization procedure was simple and did not use block design, which could be a disadvantage. Furthermore, stratification according to to sex and osteoarthritis or rheumatoid arthritis might have resulted in 2 groups with less difference.Since the number of patients with rheumatoid arthritis was higher in the LIA group, we cannot rule out that LIA or femoral block may be more effective in this patient category. The observation period of 24 h may be too short, especially with regard to adverse events. Furthermore, it would have been good to investigate whether there were differences regarding ease of rehabilitation or physical therapy.In summary, in this randomized study we could not confirm that there was any clear superiority of perioperative infiltration of local anaesthetic (LIA) over femoral block in combination with i.v. ketorolac in total knee arthroplasty, since the two analgesic regimens gave similar quality of pain treatment during the first 24 h. However, LIA may be considered the preferred option since it is cheaper and easier to perform than femoral block. In addition, LIA involves the surgeon in alleviating postoperative pain.


Objective. The aim of the study was to compare the pain symptoms of fibromyalgia patients exhibiting (FMS+PVD) and not exhibiting (FMS) comorbidity with provoked vulvodynia. Study Design. The case control study was performed in 39 patients who had been diagnosed with FMS and accepted to undergo gynaecological examination and in 36 healthy women (C). All patients completed standardized questionnaires for pain intensity, pain area, and psychological functioning. The gynaecological examination included vulvar pain pressure reactivity (Q-tip), pelvic tone assessment (Kegel manoeuver), and a semistructured interview collecting detailed information about pelvic symptoms and sexual function. Results. FMS+PVD patients displayed a higher number of associated symptoms than FMS patients. The vulvar excitability was significantly higher in FMS+PVD than in FMS and in both groups than in Controls. Half of FMS+PVD patients were positive to Kegel manoeuver and displayed higher scores in widespread pain intensity, STAI-Y2, and CESD levels than Kegel negative patients. Conclusions. The study reveals that increased vulvar pain excitability may occur in FMS patients independently of the presence of coital pain. Results suggest that coital pain develops in patients with higher FMS symptoms severity due to the cooperative effects of peripheral and central sensitization mechanisms. Fibromyalgia (FMS) is a condition of chronic widespread musculoskeletal pain characterized by steadily, diffuse, fluctuating musculoskeletal pain associated with hyperreactivity to deep pressure stimuli . The chrA larger number of women suffer from FMS with respect to men; in addition, women report multiple pain locations, heavier disabilities, lower self esteem, and poorer coping capacity than men . SeveralRecently, comorbidity of PVD and FMS has been clearly assessed –15 and iItalian  selected chronic widespread pain patients by a general screening examination and addressed them to the Psychophysics Laboratory of the Department of Medical and Surgical Sciences and Neuroscience to confirm the diagnosis of fibromyalgia. Patients completed a battery of psychophysical tests and self-administered questionnaires for the diagnosis of fibromyalgia according to ACR-90 criteria . An epidn (CES-D  and STAIn (CES-D ), assessAlgometry was used to determine positive tender points number and threshold, while Von Frey hairs were used to determine punctuate superficial pain threshold; information about pain duration, present pain intensity , and pain area and location  were colItalian current law, and has been approvedby the Scientific Committee of the Medical Faculty and by the Ethical Review Board of Siena University. The date of entry was June 2008 and the date of completion of data collection was January 2011. All participants signed an informed consent form.Thirty-six women with no malignancy, no acute or chronic pain symptoms, and no pelvic pathology or lower genital tract conditions who attended the outpatient unit of the Gynaecology Clinic  for common care were recruited as a Control group (C) of vulvar excitability. They were matched with FMS patients for age, education, marital status, number of deliveries, and occurrence of menopause. Controls underwent a complete evaluation of sexual function and were free of pain areas at the manual gynaecological examination. They denied any localized and diffuse pain and, thus, were not submitted to quantitative sensory testing . The study protocol is included in the clinical standard methods of investigation for the diagnosis of fibromyalgia in the Rheumatology Clinic, complies with the The diagnosis of provoked vulvodynia (PVD) was reached (Anna Ghizzani) throughout the history of vulvar pain elicited by light pressure. Data on genital pain, its onset, and its occurrence with intercourse were collected through semistructured interviews; in both patients and Controls gynaecological examination consisted of naked eye observation of external genitalia to rule out dermatologic abnormalities and infections.Q-tip pressure pain test evaluated vulvar reactivity and Kegel manoeuvre assessed the tonicity of pelvic floor muscles. The Q-tip test , 21, whiAll patients were examined bimanually to assess the tonicity of the muscles of the pelvic floor and specifically the pubococcygeal portion of the elevator ani (Kegel manoeuvre) . PatientThe criteria for the diagnosis of PVD were (a) exclusion of vulvar infections, neoplastic diseases, vulvar pain of gynaecological, and dermatological origin; (b) presence of pain during intercourse and/or of painful sensations elicited by light pressure stimuli applied to the vestibule in the latest 3 months or longer.n = 75) were divided in fibromyalgic , FMS with provoked vulvodynia , and Controls .On the basis of the above-mentioned criteria, participants (P < 0.05.SPSS.15 was used for MANOVAs of (a) demographical parameters, (b) questionnaires scores , (c) pain parameters and psychophysical variables, and (d) vulvar punctate pain pressure scores (Q-tip). Intercourse frequency, frequency of associated symptoms, and occurrence of pelvic floor hypertonicity (Kegel manoeuvre) were assessed through Wilcoxon test. Significance was set at The mean age of patients was 47 ± 32 yrs; demographic characteristics  as well as anxiety and depression were similar in FMS and FMS + PVD patients.Z = 2.219, P < 0.026; symptoms percentage per patient, Z = 2.009, P = 0.053).PVD was frequently observed in the FMS patients (21/39 = 53.82%). The percentage of patients with associated symptoms and the percentage of symptoms per patient  were higher in FMS + PVD than in FMS patients  and lasted at least 1 hour in 30% of them and about 24 hours in 25% of them.Multivariate ANOVA did not reveal any significant difference between FMS and FMS + PVD patients in pain thresholds at positive tender points, number of positive tender points, pain duration, pain area, pain intensity, and Von Frey superficial punctate pain threshold . The twoF = 65.192, P < 0.0001), the mean vulvar pain intensity  = 68.855, P < 0.0001), and the total pain intensity scores  = 48.792, P < 0.001).The FMS + PVD, FMS, and C groups were significantly different for the number of positive Q-tip sites  = 2.446, P < 0.024), between FMS + PVD and Controls  = 16.145, P < 0.0001), and between FMS and Controls  = 6.962, P < 0.0001).t = 2.832, P < 0.008), FMS + PVD and Controls  = 10.599, P < 0.0001), and FMS and Controls  = 5.877, P < 0.001). t = 12.586, P < 0.0001); FMS > C,  = 7.394, P < 0.0001); FMS + PVD > FMS, t = 3.666, P < 0.001).The mean Q-tip pain intensity score  was signF = 7.038, P < 0.013), STAI-Y2  = 3.966, P < 0.034) and CES-D  = 3.879, P < 0.031). Widespread pain intensity  = 4.467, P < 0.047) and not significantly different between Kegel negative FMS + PVD and FMS patients. Questionnaires scores did not differ significantly between FMS and the two FMS + PVD subgroups. Within the FMS + PVD patients, the subgroup with pelvic floor hypertonicity was significantly different from the subgroup without pelvic floor hypertonicity  = 4.064, P < 0.0001)  = 4.054, P < 0.002); Kegel positive (Mean ± SD): 54.17 ± 5.94; Kegel-negative: 41.30 ± 6.46), and depression levels  = 2.546, P < 0.05; Kegel positive: 30.50 ± 13.87; Kegel negative: 15.75 ± 7.74).Pelvic floor hypertonicity did not occur in C and FMS patients, but was present in 10 out of 21 FMS + PVD patients. Multivariate ANOVA on quantitative sensory testing values and questionnaires scores of FMS patients and FMS + PVD patients positive and negative to the Kegel manoeuvre revealed significant differences in widespread pain intensity (VAS (ntensity  was signtonicity . In fact 0.0001) , anxietyOur study shows that FMS + PVD patients display a larger number of associated symptoms than FMS patients and that most of the FMS patients exhibit increased vulvar pain excitability with respect to Controls.Compared to FMS, FMS + PVD patients show higher frequency of pelvic muscle hypertonicity very often associated with vulvar pain –27. FMS There is evidence that FMS patients may display different levels of sensitization and that the highest levels are observed in patients with multiple comorbidities . MoreoveNeuropathic mechanisms are involved in both PVD and FMS. Indeed, structural changes in vulvar innervation, consisting of sprouting between epithelial cells, increased in intraepithelial nerve endings and papillary TRPV1 afferent fibres, have been described in vulvodynia patients –32. The There is also evidence that a peripheral neuropathic component, mainly neurogenic inflammation , 39, conIt could be suggested that the vulvar hyperexcitability that we have described in most FMS patients probably represents the local expression of the generalized superficial allodynia , 19, as Our findings confirm that FMS and PVD syndromes can develop independently and that patients affected by FMS + PVD display sexual disfunctions similar to those reported by patients affected only by PVD , 49, 50.A limitation of the study is that the patients' recruitment modality does not allow to infer the epidemiological consistency of the association between PVD and FMS.In conclusion, our preliminary findings confirm the hypothesis that pain mechanisms of different origin can cooperate in worsening pain symptoms. In particular, they suggest that fibromyalgic allodynia increases the risk of coital pain.