Preemptive analgesia is considered an alternative for treating the postsurgical pain of third molar removal. The aim of this study was to evaluate the preemptive analgesic efficacy of oral ketorolac versus intramuscular tramadol after a mandibular third molar surgery.A parallel, double-blind, randomized, placebo-controlled clinical trial was carried out. Thirty patients were randomized into two treatment groups using a series of random numbers: Group A, oral ketorolac 10 mg plus intramuscular placebo ; or Group B, oral placebo  plus intramuscular tramadol 50 mg diluted in 1 mL saline solution. These treatments were given 30 min before the surgery. We evaluated the time of first analgesic rescue medication, pain intensity, total analgesic consumption and adverse effects.Patients taking oral ketorolac had longer time of analgesic covering and less postoperative pain when compared with patients receiving intramuscular tramadol.According to the VAS and AUC results, this study suggests that 10 mg of oral ketorolac had superior analgesic effect than 50 mg of tramadol when administered before a mandibular third molar surgery.Key words:Ketorolac, tramadol, third molar surgery, pain, preemptive analgesia. Third molar surgery is the most common procedure carried out by oral and maxillofacial surgeons, and it is a common model for evaluating the efficacy of analgesics for acute dental pain relief . It is oPreoperative administration of some analgesics has demonstrated reducing the onset of postoperative pain . It has Three classes of analgesic drugs have been used for pain control after mandibular third molar surgery: Local anesthetics, Non-Steroidal Anti-inflammatory Drugs (NSAIDs), and opioids ,6-10. KeThis pilot study was a parallel, double-blind, randomized, placebo-controlled clinical trial carried out in the Department of Oral and Maxillofacial Surgery of the Faculty of Dentistry, San Luis Potosi University, Mexico, following the guidelines suggested by the Consolidated Standards of Reporting Trials (CONSORT) group for planning and reporting clinical trials ; conductInclusion criteria were age 18 to 25 years, either gender, free of systemic disease, clinical and radiographic diagnosis of impacted mandibular third molar, no pain associated with the subject third molar up to the day of surgery, and grade of surgical difficulty II, III or IV. Exclusion criteria were the use of analgesics 24 h before the procedure, history of seizure disorder, pregnancy or lactation, use of oral contraceptive, and known hypersensitivity to the study medications.All subjects were informed of the possible risks of oral surgery and treatments used. Each patient accepted and signed an informed consent form. Patients were assigned sequential numbers in order of enrollment, and they received their allocated treatment according to a computer-generated randomization schedule prepared before the start of the study.Thirty patients were randomized into two treatment groups, each with 15 patients, using a series of random numbers: group A, oral ketorolac 10 mg plus IM placebo ; or group B, oral placebo  plus IM tramadol 50 mg diluted in 1 mL saline solution. These treatments were given 30 min before start the surgery. We evaluated the time of first analgesic rescue medication, pain intensity, and total analgesic consumption. The algorithm of the figure All surgical procedures were carried out in the Department of Oral Surgery by the same surgeon, and evaluations were carried out by an independent investigator. Anesthesia was by nerve block of the lingual, buccal, and inferior alveolar nerves using two 1.8-mL cartridges of 2% lidocaine containing 1:100,000 epinephrine. Once anesthesia was obtained, surgery was started. A mucoperiosteal flap was prepared by making an incision distal to the mandibular second molar along the anterior edge of the ascending ramus of the mandible . Suturing was done with 4-0 silk, and the number of sutures was documented. Mandibular third molars were classified according to the Winter Classification, in addition to the Pell and Gregory classification. Surgical difficulty was based on a modified scale of Parant, as follows: grade I, extraction with forceps and elevators; grade II, extraction by osteotomy; grade III, extraction by osteotomy and coronal section; grade IV, extraction by osteotomy, root, and coronal section . In all A 100-mm visual analog scale (VAS) was used to assess pain. The VAS consisted of an interval scale ranging from 0, representing no pain or discomfort, to 100, representing maximum pain or discomfort. The VAS report was recorded each hour for 8 h after completion of surgery, and a last evaluation was done at 24 h post-surgery. Patients were given four oral ketorolac 10 mg pills and were instructed to take one pill for rescue medication at least 6 h apart, according to their requirements. At the end of the evaluation period (24 h), patients returned the unused oral ketorolac. Pills were counted to determine the number of consumed pills and patients in each group not needing any pills. Those patients having no pain relief 30 min after taking ketorolac were given sublingual ketorolac 30 mg as a rescue analgesic procedure. Total analgesic consumption  was evaluated.Patients were asked to provide an overall evaluation of the analgesic efficacy according to a three-point categorical scale, at the end of the trial. The categories of scale were 1: poor (lots of pain), 2: fair, 3: good (minimum pain). Both patients and the independent evaluator were blinded regarding the administered treatment. Intra- and postoperative complications and adverse events were recorded.Power analysis of this pilot study was performed using the data from the VAS in the third postoperative hour as the response variable. The expected difference in means was 27.66 mm; while the expected standard deviation was 20.95 mm; including 15 patients in each treatment group and an alpha value of 0.05. Taking into consideration the data of the response variable, the power of this study was 93%.P value less than 0.05 was considered significant statistical difference.Data are expressed as mean and standard deviation, median and ranges or number of frequency and percentage. The Fisher exact test was used for to evaluate the sex, surgical difficulty, patients without needing analgesic during the period of evaluation (8 h) and patients requiring rescue analgesic procedure . For analyze the age, weight, duration of surgery, number of suture, total analgesic consumption, and the VAS scores the Student t test was utilized. The Mann-Whitney U test was used to evaluate the time of first rescue analgesic and the overall evaluation of analgesic treatments. The area under the curve (AUC) of the VAS was calculated using the trapezoidal method and was used to evaluate the overall pain intensity. A P = 0.01). In the same way, the patients of group A had less pain when compared with patients of group B, the AUC of VAS showed statistical difference (P = 0.04; Fig. A total of 35 patients were enrolled in the study of which 30 patients were included in this clinical trial. The statistical analysis was done using the data from all included patients Fig. . PersonaP = 0.02; Fig. Patients taking 10 mg of oral ketorolac plus intramuscular placebo presented lower pain intensity scores in the third and fourth post-operative hour according to VAS when compared with patients who receiving oral placebo and 50 mg of intramuscular placebo . Moreoveet al., (et al., (et al., (et al., (et al., (The results of this study shown that patients who took 10 mg of oral ketorolac had an improved analgesic efficacy according to the VAS scores as well as with the AUC of VAS, and a longer time of first rescue analgesic medication than those patients receiving 50 mg of intramuscular tramadol. Few studies have compared tramadol and ketorolac for the pain relief after oral and maxillofacial surgery -22. Gopaet al.,  compared(et al.,  carried (et al.,  and Ong (et al.,  executedThe results of this clinical trial showed that the ketorolac group had a longer period for the consumption of the first analgesic tablet after surgery when compared to the tramadol group. The data shows that 1 patient in the ketorolac group and 3 of the tramadol group did not require an analgesic during the period of evaluation. The trends of outcomes of this variable are confusing in relation to the analgesia observed for ketorolac and tramadol in this study, which could be explained by the personal variability and the subjectivity of the measurement of this variable by patient demand. The same number of patients was obtained for whom requiring rescue analgesic medication. This is in agreement with other variables in this clinical trial. It is important to note that these variables evaluating the analgesic efficacy did not show statistical difference.et al., (et al., (The superior analgesic effectiveness of ketorolac in comparison to tramadol could be explained by the pathogenesis of dental pain, which is largely inflammatory. The evidence-based medicine has shown that NSAIDs are the best analgesics for dental pain treatment . It is pet al., , 39% of (et al.,  used hig(et al., .Effective and safe analgesia is one of the many challenges in health cares. The preoperative use of ketorolac is not very common due to its inhibition of prostaglandin I2 and thromboxane A2 synthesis, which may cause peri- and post-operative bleeding . In thisIn this clinical trial five patients were excluded. These patients did not participate in the study because 2 patients presented pain associated with the subject third molar up to the day of surgery, 2 patients took analgesics a day before surgery, and 1 patient was allergic to NSAIDs.According to the VAS and AUC results, this study suggest that 10 mg of oral ketorolac had better analgesic effect than 50 mg of tramadol when administered before a mandibular third molar surgery. Further studies employing a larger sample size are necessary to confirm these finding.


Habitual postural patterns are associated with musculoskeletal pain, and improving a maladaptive posture requires postural awareness in order to lead to clinical improvements. This study aimed to develop and evaluate the psychometric properties of an innovative postural awareness scale.A 12-item Postural Awareness Scale (PAS) was developed and administered to 512 chronic pain patients  to assess its factor structure and reliability. To determine convergent validity, measures of body awareness, body responsiveness, body image, and mindfulness were correlated with the PAS, as were clinical measures of pain intensity, disability, and mental health. Sensitivity to change was assessed in 202 outpatients participating in a 10-week multimodal mind-body program.Ease/Familiarity with Postural Awareness and Need for Attention Regulation with Postural Awareness) that explained 50.8% of the variance. Cronbach’s alpha for the complete scale was 0.80; Spearman-Brown coefficient of split-half reliability was 0.67; and intra-class correlation was ICC2,1 = 0.75 . Significant positive correlations were found for body awareness (r = 0.23), body responsiveness (r = 0.41), body image (r = 0.22–0.32), and mindfulness (r = 0.38); negative correlations for pain intensity (r = − 0.14), disability (r = − 0.12), depression (r = − 0.23), and stress (r = − 0.29). Postural awareness scores increased with a mind-body program (p < 0.001); changes in the PAS were negatively correlated with changes in pain intensity (r = − 0.35) in patients with spinal/shoulder pain.Factor analysis revealed two factors (Self-reported postural awareness is associated with clinical symptoms in chronic pain patients; improvements in postural awareness are longitudinally associated with reduced pain in patients with spinal/shoulder pain. Body posture refers to the position of a person’s body in space, the alignment of body parts in relationship to one another and to the environment at one point in time, and is influenced by each of the body’s joints , 2. PostA large body of interventions aims to improve posture and postural control in patients with chronic musculoskeletal pain –12 basedWhile the links between posture and pain are highly complex and controversially discussed, studies have shown that improving habitual postural patterns might lead to improvements in musculoskeletal pain conditions and prevent chronification or further deterioration –28. ChanLauche, manuscript in preparation). The primary aims of the observational studies was to investigate the effects of either a 2-week inpatient or a 10-week semi-stationary integrative medicine treatment on chronic pain. All patients with ICD-10 diagnoses of chronic pain conditions , who were either admitted to hospital-based inpatient treatment or referred to an outpatient day care program at the same department between January 2013 and July 2014, were invited to participate. Written informed consent was obtained, and patients completed questionnaires at intake. Patients in the outpatient day care program completed additional questionnaires at discharge. The studies were approved by the University’s Ethics Committee and registered at a clinical trials register were the complete protocol for the studies can be found  before patient recruitment.This is a secondary analysis of data from two observational studies that were conducted at an academic medical center in Germany  . This measure is one of the most commonly used and best-validated instruments for self-reported body awareness and has shown excellent reliability.We used the German version of the BAQ, which measures attentiveness to normal, non-emotive internal bodily processes and sensations, specifically sensitivity to bodily cycles and rhythms, small changes in normal functioning, and anticipation of bodily reactions on 17 items scored on a 7-point Likert scale , 34 .The German version of the BRS is a 6-item instrument measuring responsiveness to bodily sensations on two scales for t scales , 35  to 100 (worst pain imaginable) . This scThe PPS measures subjectively felt pain on two scales: affective pain and sensory pain using 24 items on a 4-point Likert scale .The PDI assesses functional disability, how pain interferes with specific aspects of a person’s life using 7 items on an 11-point Likert scale .The BDI assesses depression by 21 items using 4-point Likert scales , 42 and Self-perceived stress levels in specific situations during the last month were assessed on the 10-item German version of the PSS using a 4-point Likert scale .r = − 0.107 to 0.667), an Oblimin rotation was used. Factors were extracted if their eigenvalue was > 1. Domain scores of any resulting factors and of a total score were calculated as a sum of the component item scores.Exploratory factor analysis using principle components extraction was performed to explore the factor structure of the PAS. Since most items were intercorrelated  with 95% confidence intervals [Cronbach’s α, alpha if item deleted, item-scale correlations, and item difficulty were calculated for each factor and the total score for internal consistency of the PAS. Split-half reliability was assessed as the Spearman-Brown coefficient; and two-way random intra-class correlation , mood (BDI) and perceived stress (PSS) were assessed by Spearman’s correlation coefficients. Additionally, independent predictors of postural awareness were assessed by linear forward stepwise multiple regression analyses with linear outcome and linear or dichotomous predictors. Only variables that were significantly correlated with the summary score of the respective instrument or subscale in univariate analysis were included in the initial regression model.To assess postural awareness in patients with chronic pain, the instrument’s total score and/or subscale scores were assessed and differences between samples , settings (inpatients versus outpatients) and genders (men versus women) were tested using independent t-tests; and correlated to changes in pain intensity using Pearson’s correlation coefficient.The instrument’s sensitivity to change with a mind-body intervention was assessed in the outpatient day care program sample. After baseline assessment, these patients participated in a 10-week multimodal mind-body intervention . The 60-p-value of < 0.05 (two-tailed) was considered significant in all analyses.All statistics were performed using the statistical package IBM SPSS Statistics . A A total of 512 patients  were included in the analyses. Across both studies, patients’ average pain intensity was 45.2 ± 26.1 mm on the VAS; mean pain duration was 12.9 ± 11.9 years , Cronbach’s α was 0.81, Spearman-Brown coefficient was 0.71, and intra-class correlation was ICC2,1 = 0.80, 95% CI = 0.78 to 0.83. For factor 2, which describes low levels of postural awareness and connectedness that require high efforts , Cronbach’s α was 0.77, Spearman-Brown coefficient was 0.80, and intra-class correlation was ICC2,1 = 0.81, 95% CI = 0.78 to 0.83 . In line with our hypotheses, the PAS total score as well as the two subscales were weakly to moderately correlated with body responsiveness , body image  and mindfulness (CPSS). The total score and Ease/Familiarity with Postural Awareness were additionally correlated with body awareness  was independently associated with lower pain intensity; and higher body awareness, body responsiveness, mindfulness, and vitality  was independently associated with lower pain intensity; and higher body awareness, Trust in bodily sensations, mindfulness, and vitality  was independently associated with lower depression; and higher body responsiveness, and mindfulness (Table (ty Table . The Easty Table . The Neess Table .Table 6LR2 = 0.33) was independently associated with trust in bodily sensations, mindfulness, and vitality. The Ease/Familiarity with Postural Awareness Subscale (R2 = 0.29) was independently associated with lower pain intensity and perceived stress; and higher body awareness (p = 0.034), trust in bodily sensations, and self-esteem. The Need for Attention Regulation with Postural Awareness Subscale (R2 = 0.22) was independently associated with lower perceived stress, and higher trust in bodily sensations.When limiting the sample to patients with spinal or shoulder pain, the results of the correlational analyses were more or less comparable; however correlations with pain disability were stronger and those with depression no longer were significant Table . In thisr = − 0.17; p = 0.026). However, this correlation was driven by patients with spinal or shoulder pain  and not significant for patients with other pain diagnoses .After participation at the mind-body program, the PAS total score as well as both subscales significantly increased Table . LikewisEase/Familiarity with Postural Awareness) and postural awareness and connectedness that require high efforts . The questionnaire has shown overall acceptable psychometric properties, with good internal consistency for the overall instrument, and at least acceptable consistency for the two subscales. Hypotheses-conform correlations were found for pain intensity as well as for measures of mindfulness, body awareness and body image. The PAS showed further sensitivity to change in chronic pain patients undergoing a multimodal outpatient treatment program, and those changes were correlated to changes in pain intensity in the chronic back, neck, and shoulder pain patients. However, these findings should be regarded only as preliminary, and the PAS clearly needs further validation. In order to finally judge the PAS’ diagnostic value, dimensionality  and a confirmatory factor analysis using the proposed 2-factor solution are necessary.The analysis revealed a two-factor structure of the postural awareness scale (PAS) after exclusion of one item in two samples of chronic pain patients. The two scales were comprised of six items each, describing high yet effortless postural awareness and connectedness . The Ease/Familiarity with Postural Awareness subscale reflect high postural awareness, i.e. high sensitivity to bodily cues, and connectedness to the body. Hence, the common denominator between the scales may be a trait of perceptual sensitivity and connectedness to the body more generally; independent of whether it is of interoceptive, exteroceptive, or proprioceptive nature.The factor Need for Attention Regulation with Postural Awareness however is only slightly correlated to the BAQ and the BRS subscale Trust in Bodily Sensations, but instead to the BRS subscale Perceived Connection between Mental and Physical Processes. Perceived Connection between Mental and Physical Processes reflects a common direction of an individual’s plans or wishes and their bodily desires, i.e. a low level of conflict between their cognitions and emotions on the one hand and their bodily needs on the other hand . High levels of Perceived Connection between Mental and Physical Processes, just as Need for Attention Regulation with Postural Awareness, would thus reflect a detachment between mind and body, which requires an effort to balance conscious cognitive processes and bodily needs. In the subsample of spinal/shoulder pain, the relationship to the BRS subscale Trust in Bodily Sensations is also stronger indicating that the instrument may have higher validity in patients with spinal pain alone.The second factor both factors were also correlated to subscales of the Dresden Body Image Inventory, which measures the body image, i.e. positive or negative attitudes towards the body and appearance. This correlation could reflect an association between high levels of awareness of one’s body and a generally more positive attitude towards it. Individuals experiencing themselves as disconnected from their own body can be expected to have a more negative or ambivalent attitude toward their bodily features and appearance as has been demonstrated e.g. for patients with eating disorders [Interestingly, isorders .No major differences in PAS scores have been found between male and female patients, in- and outpatients, and pain conditions . It can only be assumed that patients with chronic pain conditions might share some common features regarding body awareness and connectedness. While postural awareness has mainly been investigated in low back pain, it is reasonable that postural dysfunction might be related to a variety of musculoskeletal conditions, including osteoarthritis (with or without knee replacement) , 51 or fThis study has several limitations: First, the studies were observational trials not primarily conducted for validation purposes. Second, the sample consisted of participants with a variety of chronic pain conditions. Third, the sample further consisted of over 90% female participants. Fourth, a number of possible additional steps in questionnaire development  were not performed. Fifth, the longitudinal data were uncontrolled, which precludes any causal inferences. Finally, no objective measure of postural sensitivity/control was included as a potential gold standard, against which the construct validity of the new scale could be assessed. We therefore cannot make a definitive statement about an association between self-reported postural awareness and actual postural control.Despite these limitations, the Postural Awareness Scale (PAS) was field-tested in a large sample of pain patients, including a variety of measures for cross-validation. The PAS represents the first instrument to measure subjective postural awareness with acceptable psychometric properties. Postural awareness is associated with pain intensity, physical and mental impairments in patients with chronic pain; and improvements in postural awareness through multimodal interventions were associated with improvements in pain intensity. However, further validation in an independent sample and against objective measures is imperative before the PAS can be used in routine clinical practice and research with chronic pain patients, preferably in addition to objective measures.


OnabotulinumtoxinA has proven its efficacy in reducing the number of headache days in chronic migraine (CM) patients. The usual paradigm includes 31 pericranial injection sites with low dose (5 U) per site. The aim of this study is to present the results obtained using a simpler injection protocol of onabotulinumtoxinA, with injection sites targeted to pericranial myofascial sites of pain.Observational, open label, real-life, cohort study. We enrolled 63 consecutive patients fulfilling the diagnostic criteria of CM, and refractory to conventional treatments. The patients were injected using a “follow-the-pain” pattern into the corrugator and/or temporalis and/or trapezius muscles. The doses per muscle were fixed. According to the number of muscles injected, the total dose could vary from 70 to 150 U per session. Patients were considered responders if they had a ≥ 50% decrease in number of headache days in at least two consecutive injection cycles.Forty one patients  responded to treatment. In 70.7% of responders, the effect size was even higher, with a reduction ≥70% in the number of headache days. The associated cervical pain and muscle tenderness, present in 33 patients, was reduced by ≥50% in 31 patients (94%). Triptan consumption dramatically decreased (81%) in responders. The trapezius was the most frequently injected muscle. We observed no serious adverse event. The mean patient satisfaction rate was 8.5/10.This study provides additional robust evidence supporting the efficacy of onabotulinumtoxinA injections in CM. Furthermore, the paradigm we used, with reduced number of injection sites targeted to pericranial myofascial sites of pain, may provide evidence in favor of the implication of myofascial trigger points in migraine chronicization.NCT03175263.ClinicalTrials.gov Protocol Record I17022 ClinicalTrials.gov Identifier: Date of registration: June 7, 2017. Retrospectively registered. Chronic migraine (CM) is defined as headache occurring on 15 or more days per month for more than 3 months, which has the features of migraine headache on at least 8 days per month  and has Treatment of CM is challenging, since triptans or ergot derivatives are inconsistently effective. It requires a multifaceted approach, including lifestyle modifications, management of triggering factors, education, support, and behavioral therapy . Drug wiThe PREEMPT trials injection scheme relies on the observation that OnaA injections applied for hyperfunctional facial lines are able to alleviate migraine symptoms , and conWe present here the clinical outcome of a cohort of 63 patients treated with this paradigm of injection.In France, OnaA has not yet been approved for the treatment of CM. Since 2008, in a compassionate use, we offered these patients to receive OnaA injections on an off-label basis. Patients were eligible to OnaA treatment if they fulfilled International Headache Society (IHS) criteria for CM, regardless of whether they had an excessive abortive drug intake or not. This is in line with the current ICHD3 definition of CM in which medication overuse no longer excludes the diagnosis of CM . The patadaptation period, the injector (DR) used a follow-the-pain approach in order to determine the optimal injection scheme for each individual. The possible injection sites were the corrugator, temporalis, and trapezius muscles. Patients were systematically asked about the usual topography and time course of migraine attacks, and the existence of pain or stiffness of the cervical muscles. Examination searched for muscle tenderness and the existence of myofascial trigger points (TrPs). The decision to inject a single muscle relied on data from questioning and examination. The existence of referred pain patterns characteristic of TrPs on questioning as well as the identification of TrPs on examination were arguments to inject a given muscle. As an atlas of muscle referred pain, we used the manual by Travell and Simons [observation period started 8 weeks before the first efficacious injection and ended 2 months after the second consecutive efficacious injection, or in case of inefficacy. Throughout the adaptation and the observation phases, patients kept a headache diary where they were asked to note the days with headache and the use of rescue medication. The use of prophylactic drugs was allowed, but the dosage was maintained during the two phases. The extension period included all treatment cycles after the observation phase. During this period, the injector was allowed to modify the dosage and sites of injections using an even more tailored, follow-the pain approach.This study was an observational, open-label, cohort-study conducted in accordance with the principles of the Helsinki Declaration. We prospectively and systematically recorded data from the patients and analyzed them retrospectively. During a first phase, called d Simons . For exaThe doses per muscle, as well as the injection technique, were predetermined according to our previous experience in CM , and were off-label as well. The corrugator muscle is located in the supratrochlear region. The patient was asked to furrow his/her brow to activate the muscle, allowing an easy insertion of the needle. In order to inject the temporalis muscle, the patient was invited to chew gum, allowing to identify the most active part of the temporalis muscle. The patient was then asked to stop chewing, keeping the teeth clenched. The needle was inserted into the muscle, the extremity of the needle being directed backwards. Then, the patient was invited to relax and the dose was administered into that point. For the trapezius muscle, the injections were also protocol-driven. The dose was distributed into 3 equally-distant sites along the lower part of this muscle. So, we targeted sites of myofascial pain, which are thought to contain TrPs  but did Variation of the dosage was not allowed during the observation phase. The doses of OnaA administered to the corrugator, temporalis and trapezius muscles were respectively 5 U, 30 U, and 40 U. Thus, the overall administered dose could vary from 70 U by session if only the facial muscles were injected to 150 U if all muscle groups were injected. The 100 U vial of Botox® was reconstituted with 2 ml of saline for cervical muscles and with 1 ml for facial muscles. The choice of employing an increased concentration for the corrugator and temporalis muscles aimed to limit unwanted diffusion of the toxin to the adjacent muscles and the subsequent side effects such as ptosis. It has been demonstrated that the injected volume is a major factor affecting the diffusion of botulinum toxin, independently from the dose. In other words, the more concentrated the toxin, the more limited the spreading of botulinum toxin . AdditioIn accordance with current guidelines of clinical trials in CM , the priThe secondary outcome measures were the proportion of patients with a ≥ 70% decrease in headache day frequency, the decrease in triptan consumption, the time to efficacy onset, the duration of therapeutic effect (this was possible because retreatment was administered only when the patients needed to be reinjected ie at the time when the frequency of headache days definitely increased), and the assessment of patient satisfaction on a 0 to10 numerical scale . Data from the follow-up beyond the 2 first efficient injections were recorded.p value <0.05 was considered significant.Fisher exact test was used to compare frequencies between groups. Student t test was used to compare the means of two samples. A Sixty three consecutive patients were referred to our center for refractory CM from 2008 to 2015. All screened patients consented to receive OnaA injections and signed informed consent. They were 43 females and 14 males, aged 17 to 85 years (mean: 44.3).n = 2), living far from the hospital (n = 1), other health problems (n = 1), or personal reasons (n = 1). One other patient, aged 85 years, was excluded because of cognitive troubles making the assessment of response to OnaA difficult. Those 6 patients were included in the intention-to-treat (ITT) analysis. Sixteen patients did not respond. Forty one patients  reached the primary efficacy endpoint (a ≥ 50% decrease in headache day frequency in at least two consecutive injection cycles). In 29 out of these 41 patients (70.7%), the reduction in headache days was ≥70%, with 9 patients (22% of responders) virtually headache-free  after treatment.The optimal treatment regimen, determined during the adaptation period, included injections into the corrugator, temporalis and trapezius muscles bilaterally  in the majority of patients . In five patients the treatment was administered into both trapezius muscles only . The last three patients were injected into the corrugator and temporalis muscles only . The trapezius muscle appeared to be a key target for OnaA injections in CM, since 38 patients out of 41 (92.7%) required injections into this muscle to improve.At baseline, 15 patients did not take any triptans because of contraindication, loss of efficacy, or because triptans had never been effective. In responders, among the 28 triptan consumers, rescue drug consumption dramatically decreased (mean: 81%). Most patients reported a much better efficacy of the triptans on residual migraine attacks compared to the pre-treatment period.p = 0.002).There was no statistically significant difference between the responder and non-responder groups in terms of age, gender, mean baseline number of headache days, consumption of triptans at baseline, or the presence of prodromal, percritic or intercritic cervical muscle pain and tension Table . By contSurprisingly, the onset of efficacy was abrupt in most patients, the maximum of benefit being reached in a few days, after a latency ranging from 5 to 30 days (mean = 14.8 days). The duration of action ranged from 3 to 4 months.The injections were well tolerated. The only significant adverse event we observed was local myalgia when the trapezius muscle was injected. This pain occurred 1 to 5 days after injection, and could last up to 15 days. It was qualified as severe in 4 patients (9.7%) and, interestingly, did not recur, or recurred very moderately, during the subsequent injection cycles. We observed no eyelid ptosis, perhaps due to the high concentration (1 ml/100 OnaA Units) used in our study to inject facial muscles. The patient satisfaction was particularly high, with a mean score of 8.6 (6.5–10) on a 0–10 numerical scale.Two of the 16 patients considered to be non-responders claimed receiving retreatment because their migraine headaches were shorter-lasting, less severe, and easier to treat. Among the 41 responders, 34 are still under treatment, with a mean number of injection cycles of 5.95 (2–18). In those patients, the clinical benefit was maintained between each injection session and lasted three to 4 months. Seven patients discontinued treatment: 2 because they had achieved a sustained clinical benefit and the others due to personal reasons or lack of compliance. In this phase, patients were not required to keep a headache diary, but there was a trend towards a lengthening of intercycle intervals, and an increase in size effect with time. According to the patient pain pattern, additional muscles were injected in some patients, such as procerus, splenius capitis, suboccipitalis and masseter muscles.Myofascial pain syndromes have been described in CM patients in various pericranial sites including the neck muscles, the supratrochlear and corrugator region, and the temporalis muscles –20. ThisMost patients had not experienced an improvement of this magnitude in years, as attested by the high degree of patient satisfaction (mean 8.6/10).Our study, as well as the other recently published real-world experiments addressing the same issue –31, has Previous real-life studies provided conflicting results, with a ≥ 50% reduction in number of headache days achieved in a range as wide as 17.4 to 63% of patients –31. WithThis injection paradigm was elaborated with reference to the theory which assumes that the muscle sites with myofascial pain act as triggers to initiate or perpetuate migraine. In support of this hypothesis, it has been demonstrated that inactivation of cervical trigger points by anesthetic infiltrations or manual therapy resulted in reduced migraine number and intensity , 32–34. Cervicalgia present between migraine attacks was a major concern in our patients, present in 73.7% of cases. This is in keeping with studies that found a higher prevalence of neck pain disorders in patients with chronic rather than episodic migraine . The sigWe found that the latency of therapeutic effect was long-lasting, with a mean of 14.8 days (up to 30 days). This finding was unexpected, since the delay of action of OnaA is estimated around a few days in the classical indications of OnaA such as dystonia and spasticity . To our Our results also raise the concern of the role of drug withdrawal in the management of CM. In the present study, we found that OnaA treatment itself led to a dramatic reduction of migraine rescue medication intake (81%). Thus, we propose that, in CM patients, (i) drug abuse may be a consequence of the ancillary myofascial pain rather than the cause of migraine chronicization, and (ii) OnaA treatment should be discussed before considering medication withdrawal.We conclude that specifically targeting myofascial pain sites with selective OnaA injections may be a safe and effective option in CM treatment. Further larger, placebo-controlled studies are needed to compare the present protocol with the fixed “multipoint-low dose per point” PREEMPT protocol. If our results were confirmed by further studies, it could be suggested that myofascial pain and TrPs may contribute to headache pain in CM patients and constitute an important factor of migraine chronicization.


To identify predictive factors of response to viscosupplementation (VS) in patients with hip osteoarthritis (HOA).Prospective, multicentre, open-label trial, achieved in daily practice conditions. Patients with HOA were treated with a single intra-articular injection of a cross-linked hyaluronic acid combined with mannitol (HAnox-M-XL), using imaging guidance. WOMAC pain and function scores and patient global assessment (PGA) were assessed at baseline and day 90. Improvement, satisfaction and efficacy were self-assessed at day 90.Hip radiographs at baseline were scored using Kellgren-Lawrence grade and Osteoarthritis Research Society International (OARSI) score. Associations between clinical and radiological features and response to VS (pain improvement > 50% at day 90) were assessed in univariate analysis, and then using logistic regression, adjusted for confounding factors.p = 0.047). Radiologically, response to VS was negatively correlated with joint space narrowing (JSN) score  and was related to the patterns of femoral head migration (p = 0.008). In multivariate analysis, only JSN grade (p = 0.03) remained significantly related to a poor response.The intent-to-treat (ITT) population included 97 patients . Ninety completed the follow-up and 80 had full clinical and radiological data. Response to VS was achieved in 47.8% of patients. In univariate analysis, the only clinical outcome statistically and negatively related to response was PGA at baseline (This pilot study, which needs further confirmation by larger scale trials, suggests that radiological features might be of importance for the decision of VS in patients with HOA.ID RCB N°2013-A00165-40. Registered 31 January 2013. Osteoarthritis (OA) is the most common form of articular disease. Its prevalence is increasing and is expected to grow from 11% in 2006 to 25% by 2030  and medical history  were recorded. Other investigations included the Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC)  and patiRadiographs scoring and morphological evaluation were performed by a single experienced observer (TC). The Kellgren-Lawrence (KL) grade  and the The imaging guidance (fluoroscopy or ultrasonography), as well as the kind (complete or relative) and duration (in hours) of the recommended rest, were also recorded. In case of the use of a contrast agent, the amount injected was notified.Adverse events (AEs) were collected at each visit and categorized using the Medical Dictionary for Regulatory Activities (MedDRA). Definition of adverse events and serious adverse events (SAEs) were in accordance with the European standard EN ISO 14155: 2011. Investigators had to note all AEs on the report form. Any AE had to be assessed by the investigator regarding severity, intensity into “mild, moderate or severe”. In case of SAE, the investigator was required to declare it immediately to the sponsor on a specific form to be sent by fax within 24 h after becoming aware of the event. The investigator also assessed the causal relationship as “excluded” or “not excluded” with the treatment and/or the procedure of IA injection. All AEs whose occurrence could not reasonably be attributed to other causes that the injected treatment, were to be considered as potential reactions to it and the relationship was assessed “not excluded”.Response to treatment was defined in multiple separate ways. For reasons that will be discussed below, “responders” were primarily defined as patients who experienced an improvement >50%, 90 days after injection.Patients who were “very satisfied” or “satisfied” with the treatment.Patients who experienced a decrease in WOMAC pain score > 50%.Patients whose decrease of pain was greater than the MCII .Patients whose pain at the end of follow-up was < Patient Acceptable Symptom State (PASS) .“Responders” were secondarily defined as:XLSTAT® 2015 software  was used for statistical analysis.P < 0.20 on univariate analysis. P < 0.05 was considered statistically significant.Baseline and 3-month follow-up characteristics are presented as percentage or median [ranges]. A Mann–Whitney or a chi-square was used to assess the association of quantitative or qualitative factors and response to treatment. Multivariate logistic regression analysis was used to identify independent predictors to VS response and included sex, age, symptoms at baseline and other factors with One hundred patients were enrolled in PREVICOX study. The intent-to-treat (ITT) population included 97 patients (3 patients withdrawn from the study before injection) and was constituted of 57 females and 40 males. Ninety patients completed the study (per protocol population). Full clinical and radiographic data were available in 80 patients (X rays population). No significant difference in any demographic and clinical items was found between the 3 populations. Detailed data are summarized in Tables p = 0.009) but not with age, gender, BMI and WOMAC scores. KL score was related to disease duration (p = 0.03), WOMAC total score (p = 0.001) and PGA (p = 0.036) but not with age, gender, BMI and WOMAC pain score. There was a significant association between Ost score and PGA (p = 0.02). Total OARSI score (JSN + Ost + SC) was correlated to both PGA and disease duration but not with other items.JSN was correlated with disease duration . The same was found when comparing JSN grade 0–1 to grade 2–3 (p = 0.01). A similar trend was found for KL score but did not reach statistical significance . The decrease in WOMAC pain score was also correlated with baseline WOMAC pain score (p = 0.002), but not with baseline PGA or WOMAC total score (p = 0.07 and 0.12 respectively). This outcome was highly correlated with satisfaction and efficacy assessment (p < 0.0001).The decrease of WOMAC pain score was significantly higher in patients with JSN grade 0, 1 and 2 than in those with grade 3 .p < 0.00001), level of satisfaction (p < 0.00001), patient’s assessment of efficacy (p < 0.00001), MCII (p < 0.0001) and PASS (p < 0.0001). In the PP population 52 patients were satisfied with the treatment and 38 were not. However the number of satisfied patients with the treatment was slightly greater than that of the number of responders according to our definition (57.8% versus 47.8%) showing that the patient’s expectation and feeling are not exclusively and strictly dependent on the symptoms decrease. For instance, it is interesting to mention that 4 out of 7 (57.1%) of patients with the lowest WOMAC pain score at baseline (≤15) were not satisfied, whereas 46 out of 73 (63.0%) with WOMAC pain score between 16 and 35 at baseline were satisfied with the treatment.Patient’s self-assessment of improvement was highly correlated with the decrease of WOMAC pain and total scores (p = 0.26), BMI (p = 0.92) disease duration (p = 0.50), NSAIDS or analgesics consumption at baseline , previous steroid or HA IA injection (p = 0.30 and p = 0.19 respectively), imaging guidance , presence or lack of synovial effusion (p = 0.47), recommendation of rest the day following injection (p = 0.48), and occurrence of treatment related adverse events (p = 0.95). The only clinical data statistically and negatively related to response to treatment was PGA at baseline (p = 0.047).In univariate analysis, response to treatment was unrelated to gender (p = 0.019) and was related to the patterns of femoral head migration (p = 0.008). Forty-nine percent of the patients with supero-lateral JSN were classified as responders vs. 63% of those with supero-medial and axial JSN. Only 1 patient out of the 5 with posterior JSN was responder. No correlation was found between response to treatment and Ost score (p = 0.74), SC score (p = 0.56) and OARSI global score (p = 0.28). Correlation between KL score and response did not reach statistical significance (p = 0.18). The percentage of responders was 50% in patients without architectural abnormality, 40% in patients with hip dysplasia, 69% in patients with FAI and 62% in patients with coxa profunda. However, these differences did not reach statistical significance (p = 0.40).Radiologically, the response to treatment was negatively correlated with JSN score  remained significantly related to response to treatment, whereas the decrease in WOMAC pain score was correlated to both WOMAC pain score at baseline (p = 0.007) and JSN (p = 0.01).In multivariate analysis, only JSN grade (Nine adverse events were reported (9.18%). Three were classified as device/procedure AEs (3.1%). All 3 were described as an increase of the hip pain that occurred the very next hours after injection. Two resolved in less than 24 h with rest and paracetamol. One resolved in 1 week and needed NSAIDs. The other AES were low back pain (2 cases), sciatica (1 case), knee pain in patient with knee OA (1 case) and dizziness (1 case) and were considered as unrelated to the treatment and/or the procedure of injection. One patient, with a very high level of pain at baseline  underwent total hip arthroplasty during the follow-up.This pilot study, aimed to identify predictive factors of response of a single IA injection of HAnox-M-XL in patients with hip OA, has chiefly highlighted the role of OA severity as a predictor of efficacy. More than the KL grade, which is a composite index taking into account both JSN and osteophyte, it seems that it is the severity of JSN is the best predictor of response to treatment. In our study, patients with a JSN graded OARSI 2 and 3 had a lower rate of success as compared to patients with grade 0 and 1. This has already been suggested in a previous clinical trial .Moreover, the impact of OA severity on VS failure has been confirmed for the knee joint by the meta-analysis published by Wang et al.  and by tLikewise, patients with high WOMAC pain score and PGA score at baseline are likely to have a poorer result than those with medium pain level. Interestingly, patients with low level of pain at baseline had less successful results than those with moderate pain. The most likely hypothesis is that those patients were expecting a complete disappearance of symptoms they did not obtain. Consequently, it seems that patients should have sufficient pain level before treatment in order to perceive improvement as significant.The other trend that emerges from this study is the role of patterns of femoral head migration. Patients with superomedial and axial JSN are likely to be improved than those with superolateral or posterior JSN. This observation was not confirmed in multivariate analysis probably because of a lack of statistical power related to the too small number of patients. Likewise, despite the lack of statistical significance, the study suggests that the best results are obtained in patients with coxa profunda and FAI, resulting mostly in a superomedial axial JSN. Furthermore patients with hip dysplasia  had a lowest rate of success than those with coxa profunda and FAI or without architectural abnormality.Another interesting point to underline is the absence of influence of the BMI on clinical results. Even in patients with BMI > 30 there was no trend for a poorer efficacy of VS. This confirms that hip and knee OA are two very different entities both in terms of patient profile and in terms of treatments efficacy. Similarly, gender and age are not associated with treatment response and patients satisfaction. More interesting is the lack of influence on response of rest after injection. However the very large majority of physicians advised a relative rest for 24 h and the number of patients who were not advised to have rest is probably too small for showing a statistical difference, if there is one.The relatively small number of patients is the main limitation of the study. Another one is due to the absence of some radiographic views such as the Dunn view allowing a better evaluation of FAI, particularly for diagnosis of cam-type FAI , which mDespite some limitations this prospective study, performed in daily practice conditions, demonstrated that VS with HAnox-M-XL alleviate pain by 50% or more in more than half of patients with hip OA. The best success rate was obtained in patients with mild to moderate JSN, those with moderate pain and disability, and in case of superomedial and axial femoral head migration. This study also suggested that better results are obtained in FAI and coxa profunda than in hip dysplasia. Based on these results it is now possible to design a placebo-controlled trial to determine the real efficacy of hip joint VS.


Chronic pain as a complication following inguinal herniorrhaphy has attracted increasing attention in recent years. There is evidence that the chronic pain seriously affects patients’ quality of life. However, there are few imaging studies and diagnostic techniques of the chronic pain. The aim of this study is to explore the etiology and to analysis ultrasonographic imaging description of chronic pain following anterior open inguinal herniorrhaphy.One hundred fifty two patients with the chronic pain following anterior open inguinal herniorrhaphy were performed by ultrasonography to identify the main causes of postoperative chronic pain. Positive ultrasonic diagnoses were confirmed to be correct by the pain relieved when the patients underwent re-operation and other clinical operations. Positive diagnoses which appeared simultaneously were grouped for pairwise comparisons.P < 0.05).Two hundred sixteen positive ultrasonic diagnoses, 12 categories of postoperative chronic pain were found. They were encapsulated effusion, scrotal wall edema, testitis, hydrocele testis, restricted motion of spermatic cord at the reconstructed deep inguinal ring, varicocele, scar sutured into pubic tubercle, shrinking mesh, accumulational mesh or mesh plug, recurrent hernia, cyst of spermatic cord and epididymal cyst. In the pairwise comparison groups, encapsulated effusion with scrotal wall edema, varicocele with restricted motion of spermatic cord at the reconstructed deep inguinal ring, and shrinking mesh with recurrent hernia had significant differences in each intragroup comparisons(Ultrasonography provieds important value in the diagnosis of chronic pain following anterior open inguinal herniorrhaphy. Some positive diagnoses occur simultaneously, which is necessary for doctors to consider comprehensively. Guidelines for diagnosis and treatment of adult inguinal hernia (2014 edition) [ It was pointed out in hernia 204 editiondition)  –7. The cdition)  .The aim of our study was to explore the etiology and analyze positive findings of chronic pain after anterior open inguinal herniorrhaphy, thereby to assist in making treatment protocols in clinics.We conducted a prospectively, observational study in a single hernia center of Huadong Hospital, between August 2009 and May 2014. 539 patients who felt uncomfortable after their first herniorrhaphy were performed by ultrasonography in our ultrasound department. 152 patients who met the inclusion criteria agreed to participate in this study and signed the informed consent. This study was approved by Fudan University Ethics Committee. No statistical power calculation was conducted prior to the study. The sample size was based on the previous literature experience about the chronic pain review.pain lasting for 3 months or more” were included. Persistent chronic pain with or without local swell in the operative region or the ipsilateral scrotum was the clinical symptom of the disease. Sometimes the symptom could be relieved by holding up the scrotum.The inclusion criteria: the patients had a history of anterior open inguinal herniorrhaphy, during which artificial material was patched in preperitoneal space or the back wall of the inguinal canal was reconstructed by suturing. According to the definition of chronic pain by International Association of the Study of Pain (IASP) , cases wThe patients had laparoscope totally extraperitoneal repair(TEP) and transabdominal preperitoneal repair(TAPP) were excluded. And the patients younger than 16 years were excluded.The longest course of postoperative chronic pain in this study was ten years, and the shortest course was 3 months. Among 31 patients who had a history of bilateral herniorrhaphy, 12 patients presented bilateral chronic pain. Ultimately, a total of 164 chronic pain sites met the inclusion criteria, included 157 sites with artificial mesh, 2 sites with mesh plug, and 5 sites with suture repair.The Siemens ACUSON S2000™ color doppler ultrasound instrument, equipped with ultrasonic volume auto-scan(UVAS) and a high-frequency linear transducer ranging from 9 to 12 MHZ, were performed to scan the herniorrhaphic incisions and chronic pain sites in patients. The following parameters of UVAS were set: a volume image of 15.4 cm (length) × 16.8 cm (width) × 6.0 cm (depth) captured with a minimum slice of 0.5 mm and 250 to 400 images were collected during a single scan. The axial sequence images were automatically transferred to the ultrasonic workstation for data analysis and processing. The patients were in supine position or standing position as needed for ultrasound scanning, with the scrotums simultaneously scanned in male patients. The location, shape, and spatial structure of the mesh, peritoneum, spermatic cords, etc., were observed, with the goal of achieving ultrasonographic diagnosis of the etiology of the postoperative chronic pain.All ultrasonographic results were confirmed by the re-operation, the puncture or other clinical operations.Cases with two or more positive diagnoses were pairwise grouped for multiple comparisons.Statistical analyses were performed by STATA10 software. Values were presented as mean ± standard deviation for normally distributed variables. Positive ultrasonic diagnoses in the pairwise groups compared using a chi-square test. Statistical significance threshold was considered α = 0.05.2 = 0.35, P > 0.05).The mean age in the study was 66.10 years(± 13.82SD), ranging from 22 to 93 years old. No statistical difference was observed between genders in 93 men and 59 women , of which 14 cases were confirmed by ultrasound guided aspiration to be seroma Fig. , 2 casesThe pain was relieved or even disappeared when patients had undergone re-operation, puncture, and other clinical operations .Ultrasonography revealed that 23 pain sites were found 3 positive diagnoses in each site and 49 pain sites were found 2 positive diagnoses in each site, which resulted in 167 positive diagnoses (Table P < 0.05), which occurred more frequently than other intragroup pairwise combinations.The intragroup comparisons, grouped according to pairwise combinations of 167 positive diagnoses, showed that encapsulated effusion synchronized with scrotal wall edema, varicocele synchronized with restricted motion of the spermatic cord at the reconstructed deep inguinal ring, and shrinking mesh synchronized with recurrent hernia had significant differences within the respective groups (P > 0.05).Meanwhile, other pairwise combinations of positive diagnoses didn’t have statistically differences in the intragroup comparisons (There were 43 cases that postoperative chronic pain occurred, but no insignificant abnormalities were found on ultrasonography. These cases required continued follow-up.Ultrasonography is a fast, effective and radiation-free examination and suitable for various kinds of positions. UVAS, as a form of advanced ultrasound technology, supplies the coronal consecutive dynamic images on the basis of the two-dimensional images, plays a complementary role to the traditional ultrasound and provides the most intuitive visual plane for clinicians to work out further surgical plans . UltrasoThere are two main steps of anterior open inguinal herniorrhaphy. One is separation of the hernial sac and the spermatic cord, and the other is to reconstruct the back wall of inguinal canal by suturing or patching an artificial mesh . UltrasoBe careful to avoid the sensory nerves when the mesh is being sewed. Neuropathic pain may be due to the inguinal or genitofemoral nerves injury . UltrasoTherefore, following guidelines, standard operation and normative process are the key to reduce the chronic pain and the other postoperative complications after inguinal herniorrhaphy.Both UVAS and traditional ultrasonography have important value in the diagnosis of the chronic pain following anterior open inguinal herniorrhaphy. Some causes of the chronic pain always occur simultaneously which should be comprehensively considered by clinical doctors. Therefore, it is necessary to conside ultrasound technology as an objective basis for the assessment of postoperative chronic pain.