To evaluate the efficacy of platelet-rich fibrine (PRF) on postoperative edema and pain after impacted mandibular third molar surgery.The prospective study was comprised 30 patients who presented for the removal of bilateral impacted mandibular third molar teeth. After extraction, the sockets were filled with PRF or without PRF in the study and control groups, respectively. Postoperative edema was measured with a flexible tape measure by calculating the distance between several facial landmarks on postoperative days two and seven. Postoperative pain was evaluated with a line-type visual analogue scale (VAS) and a verbal scale (VRS). SPSS version 20.0 was used for data analysis.p > 0.05).Both groups recorded significant improvement compared to the baseline levels in almost all of the outcome variables. There was no statistically significant difference between the study and control groups  on 6 March 2017.This study was retrospectively registered at the ISRCTN registry ( Third molar surgery is one of the most common operations in oral and maxillofacial surgery. Pain, swelling, and trismus are the most common symptoms that affect patients’ quality of life. Alveolitis, infection, and hemorrhage are common complications , 2. ManyPRF clots, developed by Chouckroun et al. , are comThe aim of the study was to evaluate the effects of PRF on postoperative pain and edema after third molar surgery.This study was conducted at the Ankara University Faculty of Dentistry, Department of Oral and Maxillofacial Surgery from September 2012–May 2013. Thirty patients  aged 17–27 years were selected for removal of bilaterally impacted mandibular third molars. The local ethical committee of the Ankara University Faculty of Dentistry approved the study protocol (Date-number: 28.11.2011 - 25/1). All of the patients were informed of the nature of the surgical and experimental procedures, and their informed consent was obtained before surgery.Patients who fit the study requirements including follow up coming sessions and informed consent signingHealthy patients without significant medical diseases or a history of bleeding problemsPatients’ impacted third molars had to be symmetrical and feature the same level of surgical difficulty that required the same surgical technique to be performedThe third molars had to be in the Class I, Level B position (according to Pell &Gregory) and in the vertical positions according to Winter.Pregnant and lactating womenPatients with signs of pericoronitisPatients with chronic use of medications such as antihistamines, non steroidal anti inflammatory drugs  with clot activator was used to obtain blood from either the cephalic or basilica vein of each patient with a vacutainer needle. The blood samples were immediately centrifuged at 3,000 rpm for 10 min . After centrifugation, the PRF was gently seperated from red corpuscles.An experienced oral surgeon performed the surgical extraction with a standardized technique. Patients did not use any preoperative anti-inflammatory or antimicrobial drugs. Inferior dental and buccal nerve anesthesia was applied using a solution of 4% articaine hydrochloride and 1:100,000 epinephrine. A triangular full thickness flap with releasing incision on the disto-buccal aspect of the second molar was used. Bone removal was done with round bur. After exposing the tooth, if necessary, tooth sectioning was performed; then, the tooth was extracted with an elevator. After extraction, granulation tissue, follicular remnants, and bony spicules were removed from the socket, which was then irrigated with an isotonic saline solution. On the study side, the socket was filled with three pieces of PRF membrane, and the flap was primarily closed with 3–0 silk sutures. Pressure packs were applied. The sutures were removed on postoperative day seven. Amoxicillin (1000 mg twice per day for five days), %0.2 chlorhexidine mouthwash (twice per day for seven days) and if necessary, acetaminophen (500mg up to four times per day) were prescribed postoperatively.Facial swelling was determined by measuring distances from gonion- comissura labiorum, tragus – comissura labiorum and tragus – lateral canthus. Measurements were performed with a flexible ruler preoperatively and postoperatively day 2 and 7. For standardization all measurements were performed by the same surgeon (UG).Patients’ pain was evaluated with a line-type visual analogue scale (VAS) and a verbal scale (VRS). All of the patients completed the VAS to assess their pain, with endpoint-marked scores of 0 (no pain) to 100 (worst pain) and VRS with scores of 0 (no pain) to 5 (intolerable pain).p < 0.05). Preoperative and postoperative edema values between the groups were compared with independent sample t-tests (p < 0.05).SPSS version 20.0 was used for the statistical analysis. The pain values had an abnormal distribution; on the contrary, the edema values had a normal distribution. The preoperative and postoperative pain values between the sides were compared with the Mann–Whitney U test (p < 0.05). Preoperative and postoperative edema values between the follow-up periods were compared with paired-sample t-tests (p < 0.05).In both groups, the preoperative and postoperative pain values between the follow-up periods were compared using the Wilcoxon sign test . Nine patients were male (30%), and 21 patients were female (70%). Uneventful recovery occurred in 27 patients; however, infection was observed in three patients who were treated without PRF.Pain values measured with the VAS decreased in both groups; however, there were no statistically significant differences between the groups Table . Pain vaIn both groups, postoperative edema increased significantly in the first two days post-surgery. Postoperative edema values at postoperative day one were significantly lower than postoperative day two. However, there were no significant differences between the groups Table .Table 3EThere is a very limited amount of literature on the effect of PRF on pain and swelling in third molar surgery. The aim of the present study was to investigate the effect of PRF application on postoperative pain and edema after the surgical removal of mandibular third molars. The null hypothesis was that postoperative pain and edema with and without PRF after surgery would be equal. The authors measured and compared postoperative pain and edema after the surgical removal of impacted mandibular third molars in PRF and non-PRF sockets.PRF is the second generation of platelet concentrates (PRP is the first generation). PRF contains various autologous cytokines and immune cells; it is a fibrin membrane that covers the wound appropriately and can be sutured .In the oral and maxillofacial region, PRF has been widely used in sinus augmentation as the sole grafting material or in combination with an allograft or a xenograft.  PRF clotIn a study of 31 patients Kumar et al.  reportedIn an another study conducted on 20 bilateral impacted mandibular third molar surgeries, Singh et al. [In a multicenter study with a large sample , Özgül et al.  reportedIn a study containing 59 patients, Bilginaylar et al.  reportedUyanık et al.  extracteIn another study comprised of 30 patients, Asutay et al.  reportedGürler et al.  reportedOur study involved 30 patients who underwent bilateral third molar surgery in the same session. Bilateral operations in the same sessions may have influenced pain results . To makePRF had no significant effect on swelling and pain after lower third molar surgery, compared to the healing without it. To obtain more meaningful results, future research should use a larger sample with different evaluation methods for all variables .


The aim of this prospective study was to assess the immediate and long-term effectiveness of arthroscopic capsular release in a large cohort of patients with a precise and isolated diagnosis of stage II idiopathic frozen shoulder.All patients underwent a preoperative evaluation. Patients with secondary frozen shoulder and those with concurrent pathology at arthroscopy were excluded. This left 136 patients with a stage II arthroscopically confirmed idiopathic frozen shoulder. At each postoperative attendance, a record was made of pain, function and range of motion. At 12 months, the Oxford shoulder score was calculated, and pain and range of motion were assessed.Fifty per cent achieved good pain relief within a week and eighty per cent within six weeks of arthroscopic capsular release. The mean preoperative visual analogue scale pain score was 6.6 and the mean postoperative score was 1.0. The mean time to achieving good pain relief was 16 days following surgery. No patient could sleep through the night prior to surgery while 90% reported having a complete night’s sleep at a mean of 12 days after surgery. The mean postoperative Oxford shoulder score was 38/48 and the mean improvement was 19.2.This large series demonstrates that arthroscopic capsular release is a safe procedure, with rapid improvement in pain and a marked improvement in range of motion. Suggestions for management range from supervised neglect to corticosteroids, physiotherapy, manipulation, hydrodilatation and arthroscopic capsular release.11The term frozen shoulder was first used in 1934 by Codman, who described the common features of a slow onset of pain felt near the insertion of the deltoid muscle, inability to sleep on the affected side, and restriction in both active and passive elevation and external rotation, yet with a normal radiological appearance.11The sample size of these studies is very small: one study had just 14 patientsIt is difficult to form rational decisions on treatment because many of the studies lack exclusion criteria ; lack inclusion criteria  questionnaire, a detailed history and a standardised examination with a record of range of motion.Twenty-two patients were excluded as they had stiffness due to previous open or closed shoulder surgery, fractures or radiotherapy. This left 150 patients with a clinical diagnosis of stage II idiopathic frozen shoulder.We elected to include diabetic patients in the study as previous histological studies had shown no difference in the pathology of the capsule between diabetics and non-diabetics.All patients underwent a standardised shoulder arthroscopy by the same surgeon. At arthroscopy, a further 14 patients with rotator cuff disease  or early arthritis undetected previously by radiography were excluded. This left 136 patients with a decreased capsular volume, angiogenesis, a thickened capsule and rotator interval filled with fibrotic tissue who underwent arthroscopic capsular release. These patients were followed up at three weeks after surgery as well as at two and three months. Pain, function and range of motion were recorded at each attendance. The long-term outcome evaluation included the OSS, assessment of pain and range of motion.The arthroscopic capsular release was performed by the same surgeon throughout the study period under scalene blockade and light general anaesthesia. The arthroscopic findings were recorded in visual and written form in the notes, along with a record of the releases performed and the range of motion achieved in every plane. Multiple arthroscopic photographs were taken of each case and kept in the notes.The release started with a synovectomy of the rotator interval. Subsequently, diathermy excision of the rotator interval was performed until the extracapsular fat and the deep surface of the coracoid were exposed. An assessment was then made of the subscapularis tendon, the overlying scar tissue and the middle glenohumeral ligament. The scar tissue and middle glenohumeral ligament lying over the subscapularis were excised until the normal transverse shining fibres of the top surface of the subscapularis were exposed. The superior tendon of the subscapularis was never sacrificed. This release was continued down to the five o’clock position. Attention was then switched back to the interval and the capsule behind the long head of the biceps (LHB) was excised, up until the front edge of the supraspinatus was seen. The LHB was preserved in all patients.The diathermy probe was now passed behind the LHB, and the superior and posterosuperior capsule was divided, parallel to the joint surface, on the outer edge of the labrum, until the muscular fibres of the supraspinatus were exposed. This release was continued until the posterior portal was reached. The arthroscope was then removed and the range of motion checked. If still quite stiff, the arthroscope was reintroduced and, using a switch stick, the posterior capsule was released. Finally, 80mg of methylprednisolone and 10ml of 0.5% bupivacaine were injected down the arthroscope cannula into the joint, and a gentle manipulation completed the inferior release. Each arthroscopy was performed with good fluid input and output as well as intermittent diathermy to ensure there was no risk of chondrolysis.All patients were instructed in Codman exercisesAn unpaired Student’s t-test was used for two-way analysis of variance. Correlation between data sets was analysed using Pearson’s correlation coefficient. Frequency data were analysed using a 2×2 contingency square table and tested with Pearson’s uncorrected test. Statistical significance was set at an alpha level of 0.05.The mean age at the time of surgery was 52 years . Sixty-four patients were female. Fifty-five patients had surgery performed on the left shoulder and forty-six the right. Forty-five patients had surgery on the dominant arm. Twenty-three patients were diabetic.All patients complained of lateral upper arm pain prior to surgery. Ninety per cent felt that their pain had been relieved significantly by the surgery. Over half (51%) stated that their pain was reduced significantly in the first postoperative week. By week 6, 80% stated that they had good pain relief and at three months, 90% had good pain relief. However, 10% of patients continued to have some pain despite the intervention .Figure p=0.37 and p=0.21 respectively).The mean preoperative visual analogue scale (VAS) pain score was 6.6 (SD: 2.4) . The postoperative pain score was 1.0 (SD: 2.0). The mean improvement in scores was 5.4 (SD: 2.8). There was no statistical difference in the preoperative and postoperative VAS scores between the diabetics and the non-diabetics .The preoperative and postoperative range of movements are presented in Seventeen per cent of patients complained they had lost some of the original gain in range of movement following surgery. Seven patients stiffened to the extent that they felt the surgery was not successful. There was no significance of age, sex, preoperative movement, duration of symptoms, preoperative OSS or diabetes in this ‘failure’ group. Despite the failure, six of these seven patients were still appreciative of their treatment.p=0.74) and postoperative OSS (p=0.25) or gain in OSS (p=0.43) between the diabetic group and the non-diabetic group. There was also no correlation between postoperative OSS and duration of symptoms prior to surgery (r=-0.07). One patient had a worse pain score after the procedure and the breakdown of the OSS demonstrates a better improvement in pain scores than functional scores. However, 48% still did not score full points on the pain element of the OSS.The mean pre- and postoperative scores are shown in Seventy-four per cent of the patients were in work prior to surgery. The rest were retired (15%) or unemployed (11%). All patients who worked prior to the intervention returned to work. Thirty-nine per cent returned in week 1, fifty-eight per cent by week 2 and sixty-nine per cent by week 3  althoughOne patient had an infected portal site that responded to antibiotics. There was no deep infection or chondrolysis. There was no episode of instability or dislocation. There was no nerve injury.p=0.83).In the follow-up questionnaire, 53% of the patients described having had symptoms of frozen shoulder in the contralateral shoulder at some point since the time of operation and 32% had required treatment for frozen shoulder in the contralateral shoulder. There was no difference in OSS between patients with eventual contralateral symptoms and those without . In the present study, a clinical diagnosis made by highly experienced shoulder surgeons was shown to be wrong at arthroscopy in 14 patients (9%), who were then excluded. Other studies have demonstrated that patients with a clinical diagnosis of frozen shoulder are found to have associated pathology over 40% of the time.This study only included those patients who met Codman’s criteria for frozen shoulder with night pain that disturbed their sleep most or every night and many had received steroid injections without benefit prior to review in the specialist shoulder clinic. Consequently, this reflects those patients with significant symptoms and the indication for intervention was severe pain that prevents sleep. The study excluded patients with a secondary cause of frozen shoulder, which behaves in a different manner to idiopathic frozen shoulder.A serious failing of most studies is sample size. It has been suggested that studies into frozen shoulder should state the exact phase of the patients being enrolled and have a precise diagnosis.This study used the OSS, a validated outcome score.The OSS showed similar outcomes in diabetics and nondiabetics, yet objectively the diabetics had stiffer joints at outcome. This is likely to be due to the OSS reflecting functional range rather than extreme range. This loss of end range might not be important to elderly inactive patients but it might be important to active 50-year-old individuals.12 This study looked at early improvement and whether the early improvement was sustained. The majority (90%) of patients felt that their pain had been relieved by the surgery. Half (50%) stated that their pain had gone in the first postoperative week. By week 6, 80% stated their pain had gone.Finally, the purpose of any intervention in stage II idiopathic frozen shoulder must be to shorten the natural history of the disease process. For an intervention to have any use it must show rapid improvement  and there is no purpose in demonstrating improvement at one year’s follow-up in a condition where the natural history is for subjective improvement in at least 50% of patients without any treatment.One previous small study that included both secondary and primary frozen shoulder did demonstrate a significant reduction in pain at one week, maintained to all time points.Some might suggest that injecting 80mg of prednisolone into the joint at the end of the release could be responsible for the rapid improvement in our study. However, nearly two-thirds of the patients had already been given an intra-articular injection without any benefit.® scores, and movement have been demonstrated with intra-articular steroids as a sole treatment at four weeks.Assessing the impact of intra-articular injection of steroids in the literature is difficult for the reasons stated above . Improvements in pain, ASES and SF-36It is likely that the installation of prednisolone had a beneficial effect on pain. Nevertheless, it is unlikely that the rapid benefit seen was all due to the steroid.Interestingly, ten patients failed to get pain relief, yet nine said they would still recommend the procedure. This may be because all patients achieved some increase in range of movement and all except for one patient had some improvement in the VAS pain scores.Despite rapid early improvement in range of motion and function, 17% reported that a degree of stiffness returned during the rehabilitation phase. We attempted to see if there were any factors associated with poor outcome. There was no significant difference in the sex, age, preoperative range of movement, preoperative pain score, duration of symptoms prior to surgery, preoperative OSS or the incidence of diabetes between those patients with stiffness, who thought their operation had not been a success, and the rest of the index group.27 This study, however, would suggest that contralateral involvement may be even higher than thought previously.Contralateral involvement has been quoted in the literature as between 6% and 34%.Over a third of the patients had complained of pain that radiates below the elbow and a quarter had ‘pins and needles’ in the forearm or hand prior to surgery, both of which resolved following surgery. This has not been documented previously.The study can be criticised for using a questionnaire to record return to work if this was not recorded in the contemporaneous notes. Recall bias is known to have a significant impact on the validity of outcomes.This large study with strict inclusion and exclusion criteria has demonstrated that arthroscopic capsular release with intra-articular steroid injection and a controlled manipulation has a rapid impact on the pain, night pain and range of motion of stage II idiopathic frozen shoulder. By week 1, 50% of patients had marked pain relief and 60% had uninterrupted sleep. There was a marked improvement in function by week 3: 39% returned to work at week 1 and 58% by week 2. There was one portal site infection that settled rapidly with antibiotics. There was no deep infection; no instability or dislocation, no nerve injury and no chondrolysis. This is an effective procedure with minimal complications.


Postoperative analgesia is imperative in the youngest patients. Pain, especially if experienced during childhood, has numerous adverse effects—from psychological, through complications of the underlying disease  to an increase in the incidence of death due to the onset of the systemic inflammatory response. Peripheral blocks provide analgesia for 12–16 h, and are safer due to rare side effects that are easier to treat. The continuous peripheral block (CPNB) has been increasingly used in recent years for complete and prolonged analgesia of pediatric patients, as well as a part of multidisciplinary treatment of complex regional pain syndrome. It has been shown that outpatient CPNB reduces the need for parenteral administration of opioid analgetics. It has also been proved that this technique can be used in pediatric patients in home conditions. Safety of CPNB is based on the increasing use of ultrasound as well as on the introduction of single enantiomers local anesthetics (ropivacaine and levobupivacaine) in lower concentrations. It is possible to discharge patient home with catheter, but it is necessary to provide adequate education for staff, patients, and parents, as well as to have dedicated anesthesiology team. Postoperative period without major pain raises the morale of the child, parents. and medical staff. The pain, according to the new definition, is a disturbing experience associated with existing or potential tissue damage, with a sensory, emotional, cognitive, and social component . PostopeRegardless of immaturity, the child can feel pain since birth . The paiThe goal of analgesia in the postoperative period is to reduce or eliminate pain with minimal additional harmful effects and overall treatment costs. Adequate postoperative analgesia, especially during the first 48 h, reduces the stress response of the organism to the surgical procedure, thereby affecting endocrine, metabolic, and inflammatory changes. This reduces the incidence of postoperative complications and improves the outcome of surgical treatment  as well as on the introduction of single enantiomers local anesthetics (LA) (ropivacaine and levobupivacaine) in lower concentrations. Originally, bupivacaine had a primacy, while today ropivacaine  is mainly used because of its lower toxicity , 15, 16.However, if catheter efficiency is suspected in the immediate postoperative period, it is recommended to perform a test bolus dose of 3 ml of lidocaine 1.5% with epinephrine 1:200,000 . If tachPeripheral regional block in children has faster onset but short duration. In children under 1 year of age, nerve fibers are thinner, myelination is scarce, and Ranvier’s nodes are closer. The volume of distribution is higher , 21, cleCatheters are placed in sterile conditions with the help of a nerve stimulator (4.6%), ultrasound (30.2%), or a combination of these two techniques 62.9%) . Placeme% . PlacePatient satisfaction is a very important indicator of the quality of treatment and higher pain control satisfaction score (PCSS) is an indicator of better patient care. Pediatric patients have expressed satisfaction with the popliteal CPNB . For theIn a study by Visoiu M et al., 31.4% of patients did not have pain and did not receive any additional analgesics during their stay in PACU. After the release from the hospital, 25% of the patients did not have any pain at home, although 97% of patients received at least 1 dose of opioids . AccordiContinuous peripheral block does not exclude the additional use of opioids . In the Perineural catheter technique is used in chronic pain. The management of patient with CRPS is integrated in a multidisciplinar approach associating pain management with physiotherapy treatment and psychological management. The keys to success are active physiotherapy treatment and restoration of normal limb movement to which CPNB may contribute. Recurrent CRPS remains a therapeutic challenge in pediatric patients. Dadure et al , reporteComplications are rare and minor, mainly mechanical , and nausea and vomiting . So far,In the study by Visoiu et al., 14.4% of patients had subsequent catheter-related complications, mainly minimal catheter leakage that did not affect the analgesic effect . Dadure Visoiu et al. reported that 28% of patients had postoperative nausea/vomiting and/or itching . The tecIn the study by Walkers et al. , there wMany complications  are difficult to diagnose in infants and nonverbal children who cannot describe their symptoms accurately. Nevertheless, in a study by Polaner et al.  the inciKrane and Polaner believe that it cannot be determined whether the rare symptoms of LA  are objective or only placebo responses in children who are told to pay attention to these symptoms of LA toxicity .Absolute contraindications for placement of perineural catheters are: allergy to local anesthetic and infection at the site of planned puncture. Relative contraindications are sepsis, prolonged PT and PTT, heart failure, neurological diseases, and patient refusal. Due to the small number of contraindications and improvements in the clinical, economic, and humanistic approach, perineural catheters are used more often nowadays .Regional anesthesia is commonly used in addition to general anesthesia to provide adequate postoperative analgesia and better comfort. It provides sufficient analgesia and better comfort and it is rarely performed in a wake state. Postoperative course without the significant pain raises the morale of the child, parents, and medical staff. The surgeon as well as the anesthesiologist is pleased to see a peaceful, alert and cooperative child in the immediate postoperative period. From an ethical point of view, it is not justifiable to allow the child to suffer pain, when simple and safe techniques of regional anesthesia are easily complementing or replacing conventional-general anesthesia. The goal of a physician should always be to minimize the psychological and physical trauma of the patient, regardless of how young and immature the child is. Hospital stay will be forever remembered as a traumatic experience if pain is not adequately treated. Therefore, proper care of pain is of great importance.The use of any technique of regional anesthesia depends on the estimated risk/benefit ratio. No published study reported sustained neurological complications or serious side effects after use of CPNB. It is possible to discharge patient home with the catheter, but it is necessary to provide adequate education for staff, patients, and parents, as well as to have dedicated anesthesiology team. It is extremely important to organize adequate monitoring of these patients by phone calls and visits by trained medical workers. Regardless of the numerous ethical and security problems in the design of pediatric studies, more prospective studies are needed to provide adequate evidence.DS: conceptualization, investigation, project administration, visualization, and wrote the manuscript. MS: investigation, visualization, literature review and wrote the manuscript. ZS: literature review, providing regional anesthesia, visualization and investigation. IS: placing perineural catheters, providing regional anesthesia, visualization, and investigation. SD: investigation and supervision. IP: providing regional anesthesia, language supervision and made a final version of manuscript. MM: visualization, analysis of literature, and investigation.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.


To compare the analgesic effect of anesthetic infiltration of lidocaine 2% and low-level laser therapy (LLLT) by GaAlAs into tender points of patients with orofacial pain and fibromyalgia (FM).A randomized clinical trial was performed with adults (N=66) that were allocated into two groups (1:1): Group A received LLLT irradiation by Diode Laser GaAlAs (780nm) with expositions twice a week during six weeks and Group B was treated with anesthetic infiltration of lidocaine 2% without vasoconstrictor once a week for four weeks. The pain assessment included the Visual Analogic Scale (VAS) and tenderness to palpation.p=0.0001, β=1.0), even though no statistical difference was found between both treatments . The presence of tender points decreased after both treatments, with responsively in some types of masticatory muscles (p<0.05) except posterior temporalis muscle. The patients’ perception showed that both treatments were effective and a few patients reported that the treatment did not improve welfare.No dropout and adverse effect was observed during the study. The pain decreased significantly in each group after the treatment (The LLLT by GaAlAs and anesthetic infiltration of lidocaine 2% were equally effective to control orofacial pain in FM individuals. Key words:Facial pain, myalgia, rheumatic disease, local anesthesia, phototherapy.  Fibromyalgia (FM) is a chronic musculoskeletal condition characterized by generalized pain with sensitivity to palpation in 11 or more of the 18 points at specific body locations (tender points) during at least 3 months (American College of Rheumatology - ACR) ,3. DespiAlthough the etiology and pathophysiology of fibromyalgia are unclear, some hypotheses have been postulated. Some authors have described the etiology as a dysfunction of central nervous system, a reduction of activity of hypothalamic-pituitary-adrenal axis or a dysfunction of skeletal muscle nociception . MoreoveAs the cure for fibromyalgia is unknown, therapeutics should aim to reduce pain and provide a holistic approach for the patient and their family. In this context, a variety of treatment options to relieve fibromyalgia symptoms was proposed, such as instruction for the patient, psychotherapy, exercises, alternative medicine, pharmacologic therapy and LLLT ,8. Howevet al.  and follows the CONSORT  statement for randomized clinical trials .- Ethical ConsiderationsThis study was approved by Ethics Committee in Research of Federal University of Paraiba (CAAE: 08523712.6.0000.5183) and followed all the recommendations of Helsinki Declaration. The clinical approaches that might cause any possible discomfort or risk were fully explained to the individuals. All the individuals who accepted to participate in this study signed a free and informed consent.- Sample et al. , located in a small capital of the Northeast of Brazil.The sample was allocated into 2 groups (1:1): Group A (n=33) received LLLT and Group B (n=33) was treated by anesthetic infiltration. The block randomization was performed in Microsoft® Excel® 2016 software after the codification of each volunteer. This phase was accomplished by a research blinded and every member of the population had an equal chance of being chosen.- Eligibility Criteria To be eligible for this study the patients had to fulfill the fibromyalgia diagnosis criteria from the American College of Rheumatology 1 and the myalgia diagnostic criteria for temporomandibular disorders (DC/TMD) . The diaThe exclusion criteria considered patients who changed their systemic medications 3 months before the beginning of the treatments, those who related the previous experience of an allergic reaction to lidocaine or do not agree to participate voluntarily in this research. During the treatments, if any alteration of the systemic medication were indicated by the responsible rheumatologist, the subject would be excluded from this research.- Study Design and Interventions A parallel, controlled and randomized clinical trial design was performed with 66 adults of both genders (62 women and 4 men). The first author performed both types of treatment. Two evaluations, one qualitative e another quantitative, were carried out to test treatments’ effectiveness. The quantitative information was the measurement of orofacial pain intensity using the VAS. The VAS was self-completed by the respondent that placed a line perpendicular to the VAS at the point that represented their pain intensity. The pain scores reported by the patients ranged from 0 (no pain) to 10 (intense pain). These analyses were conducted on two occasions: at the beginning (1 day before the start) and at the end of the treatments (1 day after the ending). The measure of VAS considered the pain at rest or during the function in the last 15 days.et al.  that used manual palpation with the perpendicular pressure of two or three fingers on the surface of the skin, at approximately 4.0 kg/cm2 as suggested by Wolfe et al. . This evBefore the treatments, the skin of the individuals was disinfected with 70% alcohol and marked with a permanent marker at the points assessed in baseline evaluation. Treatment in Group A consisted of irradiation with Diode Laser GaAlAs (Twin Flex® MMOptics) based on a wavelength of 780nm, 50mW of power, Energy 2J (Dose 50J / cm2), spot 0,04cm2. The LLLT was applied precisely and continuously into the selected points during approximately 40 seconds. The patients were exposed to the laser application in a spot-skin distance of 1 cm while seated in a dental chair with their necks supported, two weekly sessions, during six weeks, for a total of twelve sessions. In the Group B, the individuals were treated by anesthetic infiltration of lidocaine 2% without vasoconstrictor (Lidostesim® SV). Carpule syringes with reflux and 30-G short needles  were used in the procedure. A volume of 0.5 ml of lidocaine was infiltrated into each tender point and stretching was made after all the injections in order to help to distribute the solution across the muscle. The treatment in Group B was repeated once a week for four weeks.The volunteers fulfilled a questionary after treatment conclusion to assess information regarding the perception of the effectiveness of both treatments and well-being. The questionnaire was structured with categorized questions (Yes or No) and following this sequence [1] In your opinion, do you think this treatment effective? [2] Do you think that this treatment improves your well-being? The questions were answered individually at the clinical office without any patient identification to control any possible bias.- Statistical Analysis The primary outcome were the level of pain (VAS) and the incidence of pain before and after the treatment. The secondary outcome considered the individuals’ perception. The statistical analysis was carried out in SPSS software version 23.0 . Data were analyzed using descriptive and inferential statistics. Normality was obtained by the Shapiro-Wilk test. A comparative exploration of the treatments considering VAS was performed by Student t-test. The paired t-test was used to compare each treatment within the same group (before and after). The posthoc analysis accessed the β-1 value (effect size) using the software G*Power 3.1. McNemar’s test was used to access the difference between the presence of tenderness before and after the treatments. The level of significance adopted was 0.05 considering a two-tailed test.p-value > 0.05. p=0.0001, β=1.0), even though, no statistical difference was found between both treatments .All the volunteers completed the study. There were no adverse effects reported under the conditions of this study. The average age was 46.14 (± 10.91) years, with 76% of these individuals diagnosed with FM in the last 5 years. There was no significant difference between the age and gender of participants in both groups, with p<0.05), except for the posterior temporal muscle that did not show significant difference after the applications (p>0.05).The patient’s perception showed that both treatments were effective, with 100% of positive response in Group A against 97% in Group B. Regarding the well-being after the treatment, 3% (n=1) of the patients in Group A related that the treatment did not improve welfare. This fact was also observed in Group B with higher proportion 18% (n=6) . None ofThis randomized clinical trial was designed to specifically compare the treatment outcome of a pharmacological and a non-pharmacological approach. Two important parameters of orofacial pain were assessed as the intensity of pain by VAS and the presence and localization of tender points by palpation, both recommended by American Dental Association (ADA). Tender points are considered the primary clinical and diagnosis parameter of symptomatology of FM, which provides a reliable indicator of orofacial pain ,22. In ap<0.05), with 64% in Group A and 61% in Group B, without statistical difference between both treatments . The LLLT .It can be concluded that this particular type of LLLT using GaAlAs  with the protocol of applications twice a week during 6 weeks and the anesthetic infiltration of lidocaine 2% with once a week usage during four weeks were equally effective approaches to pain reduction in individuals with orofacial pain and FM. However, the usage of LLLT might be more interesting considering the patient’s comfort.


Chronic Pelvic Pain (CPP) and Chronic Pelvic Pain Syndrome (CPPS) have a significant impact on men and women of reproductive and nonreproductive age, with a considerable burden on overall quality of life (QoL) and on psychological, functional, and behavioural status. Moreover, diagnostic and therapeutic difficulties are remarkable features in many patients. Therefore evaluation, assessment and objectivation tools are often necessary to properly address each patient and consequently his/her clinical needs. Here we review the different tools for pain assessment, evaluation, and objectivation; specific features regarding CPP/CPPS will be highlighted. Also, recent findings disclosed with neuroimaging investigations will be reviewed as they provide new insights into CPP/CPPS pathophysiology and may serve as a tool for CPP assessment and objectivation. Pain is an unpleasant sensory and emotional experience associated with actual or potential tissue damage or described in terms of such damage . ChronicNotably, EAU guidelines underscore the fact that central sensitization mechanisms and Central Nervous System (CNS) neuromodulation and neuroplasticity are relevant pathophysiological mechanisms in CPP/CPPS, and indeed many patients (up to 50% in some cohorts) report neuropathic pain symptoms –10. In pWhile acute pelvic pain is considered as the fifth vital sign , 15 in tChronic Scrotal Pain is as well a likely underestimated syndrome, with reported prevalence ranging between 2,5 and 5% , 32, 33.Pelvic Floor Muscle Pathology and widespread muscle tenderness deserve particular mention; they are recurrent features both in men and women affected by CPP/CPPS, as well being internal and external Pelvic Tender Points –38. ObjeAlthough epidemiologic data vary in this great magnitude, CPP represents a significant socioeconomic problem, since Pelvic Pain Syndromes do have an impact on QoL and often result in depression, anxiety, impaired emotional functioning, and fatigue –44. SexuPelvic pain affects women more frequently than men because of genetic, hormonal, sociocultural, environmental, and anthropological aspects. From an evolutionary perspective, men have always been “warriors and hunters” and consequently they more often experienced somatic pain, which is qualitatively and quantitatively different from visceral pain. Otherwise, visceral pain has always been reported mostly by women because of menstrual-related pain and painful delivery experiences.κ receptor mediated analgesia than men . Furthermore, they are less sensitive to pain modulation, and female pain threshold is lower than that of men (quantitative aspect) [β-estradiol and progesterone, are able to influence the levels of PGE2 and CGRP in the Periaqueductal Gray (PAG) [β-estradiol and/or progesterone augments PGE2 and its EP3 receptor, and PGE2 plays a role in regulating the expression of CGRP in the PAG. Different levels of 17β-estradiol were also able to influence the release of CGRP from murine F11 cells [β-estradiol and pain mediators was documented in a female mice model of temporomandibular Joint arthritis [β-estradiol upregulates both NGF and TRPV1 in a dose-dependent manner, and, in particular, synovial TRPV1 is involved in allodynia of temporomandibular joints and was responsible for COX-2 overexpression in inflamed joints. Such results seem to be relevant both for pathophysiological mechanisms of pain and also for the future development of new therapeutic pharmacological targets. Testosterone, on the other hand, is also known to be relevant in both behavioural development and pain modulation mechanisms, as it has been demonstrated in murine models that opioid analgesic sensitivity is influenced by testosterone levels even in early life in parallel with sexual differentiation of the reproductive system [κ and δ receptors and the pain modulating descending noradrenergic pathways seem to be implicated [From a biological and pathophysiological point of view, women complain of pelvic pain more than men because of both qualitative and quantitative differences in pain modulation pathways. In fact, women are more sensitive to opioid  aspect) , 16, 51. aspect) . Further aspect)  and can  aspect)  in orderay (PAG) ; moreove11 cells . Moreoverthritis . It was e system . Other me system , and it e system , thus coplicated –62. DespAs mentioned earlier, CPP and CPPS are a major burden for patients and moreover imply diagnostic and therapeutic difficulties in many cases: that is, up to 55% of women with CPP/CPPS have no clear and definite pathological findings even after laparoscopic evaluation , 63. NotTake-Home Message. Many patients, both male and female, suffer from CPP/CPPS during their life span. CPP/CPPS is accompanied by psychosocial and mood disturbances, worsened sexual functioning, decreased overall QoL, and occasionally even catastrophizing features. Despite this, CPP and CPPS are subtle, underestimated, and underdiagnosed clinical conditions; also, as different features are often present in the same patient , correct and satisfied management of patients is seldom feasible. Moreover, as in other pain syndromes, objectivation and evaluation of pain are often troublesome both for patients and physicians.Besides anamnestic interview and clinical examinations, pain scales and questionnaires are useful and reliable tools to assess pain intensity, and moreover some questionnaires also allow the distinction between nociceptive and neuropathic pain in patients presenting with more complex painful syndromes. Notably, several scales and questionnaires have been developed over years and the choice for the proper one depends on clinical settings; patient's gender, age, and education; and physician's personal experience. We also will review some QoL and psychological assessment questionnaires, as CPP and CPPS often have a detrimental impact on patients' daily activity and represent a considerable burden on emotional and psychological processing. Moreover, as discussed above, patients presenting with associated psychological features besides CPP/CPPS often have poorer pain control and worse clinical course than patients without these features. Recently, some criteria for the reevaluation of scales and questionnaires in chronic pain patients have been proposed . The proMonodimensional pain scales are a simple yet useful tool for a “raw” first assessment of pain. As they merely consist of a value of patient's experienced pain, they are not suitable to reveal the quality of the painful experience or to differentiate nociceptive from neuropathic features of pain. Nevertheless, they are still useful for both acute  and chroThese questionnaires allow a more complex pain evaluation beyond asking the patient to merely evaluate the intensity of the painful experience; other relevant features are investigated. The nature and location of pain are assessed, along with the esteem of the impact of pain on daily life activities and mood. Multidimensional pain scales are therefore a useful tool for chronic pain evaluation.Mc Gill Pain Questionnaire (MPQ) is a widespread multidimensional pain questionnaire. MPQ assesses the intensity of the present pain with a 0–5 scale; moreover, it allows examining pain distribution with a picture representing the human body on ventral and dorsal planes suitable for pain distribution mapping. Further, pain qualities and psychological processing are described by the patient by answering a series of specific questions divided into clusters  . As MPQ,In order to distinguish nociceptive from neuropathic pain features, properly tailored, adequate therapy and screening tools for neuropathic pain are also useful in CPP/CPPS patients; besides the interviews, some tools also include physical tests and examinations. The Neuropathic Pain Scale  examinesSpecific questionnaires for assessment and evaluation of CPP/CPPS have also been developed, both for diagnostic and therapeutic purposes. Pelvic Pain and Urgency/Frequency Questionnaire (PUF) is a self-report questionnaire designed to investigate the presence of urinary urgency/frequency, pelvic pain, or sexual dysfunction in both sexes and specifically developed by C. Lowell Parsons for the study and diagnosis of Interstitial Cystitis . It examines both a symptom score (which measures how often a patient experiences problems) and a bother score (how much symptoms bother the patient); combination of both scores is the total PUF score. Score range is between 0 and 35 and a score equal to or greater than 12 is suggestive for the disease in question even if further diagnostic urological, gynaecological, or urogynaecological evaluations are needed. It was, in fact, demonstrated that high scores may be compatible with different diagnoses such as urinary tract infections or overactive bladder syndrome . To dateRecently, a novel phenotyping system for urological CPPS has been developed, the UPOINT system . The acrFinally, a dedicated questionnaire has also been proposed for Vulvodynia patients , which mCPP and CPPS are, according to their definition, usually associated with detrimental effects on overall QoL and with psychological comorbidities. Moreover, it has been shown that psychological impairment per se is responsible for worsened symptoms and is a predictor for bad therapeutic outcome see . TherefoSeveral questionnaires explore the impact of pain symptoms on QoL in order to provide more complete management of the Chronic Pelvic Pain. Quality of life is best defined as patients perception of and reaction to their health status and nonmedical aspects of their lives . QoL is measured with a collection of items, scales, domains, and instruments. In particular, instruments are classified as generic , disease-specific, site- or region-specific, dimension-specific , or utility measures . To ensure an appropriate evaluation, the use of a disease-specific instrument in combination with a generic instrument should be recommended . Short FRegarding psychological status, anxiety, depression, and catastrophizing may be assessed with proper questionnaires as well . PatientTake-Home Message. Pain scales and questionnaires are fundamental tools when approaching, assessing, and evaluating CPP/CPPS patients. Mono- and Multidimensional scales are useful tools for patient assessment, for trials enrolment, and for therapeutic outcomes. CPP/CPPS specific questionnaires and indices are as well unneglectable tool for CPP/CPPS evaluation, as assessment and therapeutic interventions are better guided by scoring systems such as the UPOINT system. Finally, psychosocial and QoL scales as well should be borne in mind, as several patients report detrimental effects of CPP/CPPS on psychosocial functioning and overall QoL.As mentioned above see , neuropaAlgometers have previously been used for the definition of the Myofascial Pain Syndrome (which may be responsible for CPP)  with theδ, and C fibers and producing threshold values for the current perception in such bladder afferent fibers. Men suffering from CPPS were also evaluated using Neurometer CPT [Some authors investigated CPP/CPPS patients with Neurometer Current Perception Threshold (CPT) analysis in order to objectivate neuropathic features in such patients. Neurometer evaluations were firstly performed in male and female healthy subjects in order to assess Current Perception Thresholds in the lower urinary tract . Neuromeeter CPT  althoughUnfortunately, only a limited number of investigations have been performed in order to reveal neurophysiological abnormalities in CPP/CPPS patients. Laser Evoked Potentials (LEPs) are one of the most reliable laboratory tools to objectivate and diagnose neuropathic pain , but no Take-Home Message. QST provides integration for the regular neurological examination, giving the opportunity to better objectivate neurophysiological abnormalities in CPP/CPPS patients by establishing pain thresholds. Algometry allows optimal standardization of QST, as it gives reliable and precise quantification of the administered stimulus and the subsequent threshold. Electrophysiological evaluation, with SEP and/or EMG, may further help to objectivate neurophysiological anomalies in CPP/CPPS patients. Despite these promising features, only a few studies have been performed, and therefore further investigations are warranted to elucidate the real importance of these tools when evaluating CPP/CPPS patients.In recent years, Magnetic Resonance Imaging (MRI) and functional MRI (fMRI) have been suggested as tools to diagnose and objectivate chronic pain, as characteristic abnormalities have been detected in several chronic pain syndromes –141.In the same manner, several studies assessed brain abnormalities with fMRI protocols in different CPP/CPPS patients both for pathophysiological and for therapeutic meanings. In particular, Endometriosis patients were evaluated with different neuroimaging protocols. Proton spectroscopy and seed-based resting functional connectivity MRI were used to determine whether women with Endometriosis display differences in insula excitatory neurotransmitter concentrations or intrinsic brain connectivity to other pain-related brain regions . CompareFurthermore, brain connectivity was evaluated in Endometriosis patients with resting-state fMRI imaging, before and after psychotherapeutic protocols . It was http://www.mappnetwork.org/) is a multicenter collaborative research group established to conduct integrated studies on participants with urologic Chronic Pelvic Pain Syndrome (UCPPS) [Besides patients with Endometriosis, patients with urologic CPP were evaluated in several neuroimaging protocols. The Multidisciplinary Approach to the Study of Chronic Pelvic Pain (MAPP) Research Network ( (UCPPS) . The aim (UCPPS) . The lef (UCPPS) , 148. Wh (UCPPS) . SimilarThe MAPP study group also enrolled men with Chronic Prostatitis/Chronic Pelvic Pain Syndrome comparing them to healthy controls. With resting-state FC analysis, significant group difference was observed in the functional connectivity between pelvic-motor and the right posterior insula . It was Vulvodynia patients have also been recently investigated with fMRI scanning  , and altPrimary Dysmenorrhea (PDM) women were also enrolled in several neuroimaging protocols. Voxel-based morphometry analysis showed abnormal volumetric decreases in regions involved in pain transmission and higher level sensory processing and affected regulation, while volumetric increases were found in regions involved in pain modulation and in regulation of endocrine function . The samAll these investigations document how CPP and CPPS, rather than being merely urogynaecological syndromes, have fundamental neural pathophysiological mechanisms, as neuroimaging abnormalities have been identified in several cohorts of patients. These alterations may possibly reflect sensitization processes and neuroplastic modifications in Central Nervous System, which are subsequent to the chronic painful stimulation arising from the periphery. It is also possible that some patients, that is, SNP carriers, have alterations in cortical circuitry that predispose them to the development of chronic pain syndromes such as CPP. Of course, other researches are warranted to better understand the alterations in CPP patients' brain and to properly match the neuroradiological findings with clinical and possibly genetic assessments. Nevertheless, brain neuroimaging in CPP patients appears to be a promising field as it offers the future possibility of a reliable noninvasive marker of CPP and CPP severity.Take-Home Message. Being similar to other patients with chronic pain conditions, CPP/CPPS patients showed several structural and functional brain neuroimaging abnormalities. Anomalies were found in both male and female CPP/CPPS patients. Therefore, brain neuroimaging appears to be a promising tool for further evaluation of CPP/CPPS patients both for pathophysiological and for diagnostic/assessment purposes, although further researches are surely warranted to fully understand the correlations between CPP/CPPS symptoms and brain functional and structural anomalies.Despite the development of several screening and diagnostic tools, pain evaluation and objectivation still remain not seldom troublesome in CPP/CPPS. Nevertheless, a full and correct assessment of patients' painful experience can help physicians to properly develop appropriate therapeutic protocols specially tailored for those patients, taking into account pain symptoms as well as eventual comorbidities, psychological features, and functional QoL status. Future investigations are warranted to ameliorate diagnostic tools accuracy and to correlate instrumental findings.


To determine characteristics associated with monthly chest pain and shortness of breath (SoB) during activity in cardiovascular disease (CVD) and trajectories of these symptoms over 10 months.Baseline questionnaire was sent to patients aged ≥40 years from 10 UK general practices. Responders were sent monthly questionnaires for 10 months. For patients with CVD (ischaemic heart disease and heart failure), the association of sociodemographic characteristics, pain elsewhere and anxiety and depression with monthly reports of chest pain and SoB during activity were determined using multilevel, multinomial logistic regression. Common symptom trajectories were determined using dual trajectory latent class growth analysis.661 patients with CVD completed at least 5 monthly questionnaires. Multiple other pain sites  and anxiety or depression  were associated with reporting weekly chest pain. Anxiety or depression , obesity , older age , increasing number of pain sites  and female gender  were associated with reporting weekly SoB. Eight symptom trajectories were identified, with SoB symptoms more common than chest pain.Potentially modifiable characteristics are associated with the experience of chest pain and SoB. Identified symptom trajectories may facilitate tailored care to improve outcomes in patients with CVD. This was a large study of primary care patients with diagnosed cardiovascular (CVD) disease.It is the first study to examine the course of CVD symptoms based on monthly self-reported data.There was attrition, with many patients not completing sufficient monthly questionnaires to be included in the analysis.Due to the nature of the questionnaire data, we were unable to identify the number or the duration of the monthly symptom episodes.Chest pain and shortness of breath (SoB) are common symptoms of cardiovascular disease (CVD) seen in UK primary care. The incidence of chest pain ranges between 13 and 20 per 1000 person-years,7Though directly associated with CVD, chest pain and SoB may also be experienced due to non-cardiac reasons. In a US sample of 10 881 participants with no prevalent CVD or pulmonary conditions, 22% reported SoB,Symptoms of chest pain and SoB are not typically isolated events. Assessing how patients’ symptoms co-occur and change over time may help identify common patterns (trajectories) of these symptoms that may be related to long-term outcomes. However, how the experience of chest pain and SoB in patients with CVD varies over time remains unclear. Other trajectories of symptoms have previously been determined to aid understanding of the course of morbidity, for example, in back pain.The objectives of our study, in a primary care population with CVD, were; (1) to determine the association of patient characteristics with the monthly experience of chest pain or SoB during activity and (2) to determine common trajectories of chest pain and SoB symptoms over time.This analysis uses data from the Comorbidity Cohort (2C) study. A prospective cohort study, this was designed to investigate the interaction between CVD and osteoarthritis (OA) comorbidity over 12 months. Full details of the 2C study are reported elsewhere.This analysis focuses only on those patients with recorded CVD (with or without comorbid OA) of which there were 2858 sent a baseline questionnaire. These patients were identified through a primary care record of ischaemic heart disease (IHD) or HF using Read codes (commonly used to record morbidity in UK primary care) within a 3-year period prior to the baseline questionnaire, starting from November 2006. IHD was identified by Read codes starting G3 (‘Ischaemic heart disease’), and HF was identified by Read codes starting G58 (‘Heart failure’) and codes related to the New York Heart Association classification (codes 662f-i).The primary outcomes were monthly self-reported measures of two CVD-related symptoms: (1) chest pain during activity and (2) SoB during activity. A single-item question was used for each symptom, both based on existing, valid outcome measures , general physical health, pain elsewhere and anxiety and depression. BMI was categorised as: normal weight (<25), overweight (25–30) or obese (30+). General physical health was measured using the 12-item Short-Form Health Survey.Baseline chest pain and SoB were measured using yes/no responses to items enquiring about any chest pain or tightness in the past 4 weeks, and any SoB in the past 4 weeks.The statistical analysis was performed in two phases. The first phase examined associations between baseline sample characteristics and monthly chest pain and SoB experienced during activity. The second phase clustered patients into groups based on the most common patterns (trajectories) of chest pain and SoB experienced over the 10-month follow-up time period. Responders who had completed chest pain or SoB items on at least 5 of the 10 monthly questionnaires were included in the analyses.A multilevel, multinomial logistic regression model (monthly measurements nested within respondents) was used to determine associations between the baseline sample characteristics  and monthly chest pain during activity (1–3 weeks vs none and 4+ weeks vs none). Associations were initially unadjusted, followed by adjustment for covariates. PCS score was not included in the multivariable model due to strong association with age and pain elsewhere. Interactions between time and covariates that were found to be statistically significant were incorporated into the model to assess whether their effects changed over the time period. The same analysis was then repeated for SoB.Sensitivity analyses were performed using respondents who completed the chest pain and SoB items on at least 2 monthly questionnaires and by using multiple imputation (with 50 imputations) to impute the missing monthly questionnaire answers and any missing covariate data.Dual trajectory latent class growth analysis (LCGA) was carried out to group (cluster) respondents into the most common trajectories of self-reported chest pain and SoB over the 10 months using the repeated monthly measures of the two symptoms.There is no definitive method of deciding on the most appropriate number of clusters using statistical goodness of fit measures. We initially used Akaike’s information criterion, Bayesian information criterion (BIC) and the adjusted BIC, and for each of these, the model with the lowest goodness of fit value indicates the optimal number of clusters. The final decision on the optimal number of clusters was determined by a combination of statistical information, the size and distinctiveness of the clusters and how well the profile (monthly responses of chest pain and SoB) of respondents matched the cluster. Respondents were allocated to the cluster for which they had the highest posterior probability of belonging. The mean of these posterior probabilities for respondents assigned to each cluster ) was determined. An AvePP greater than 0.7 suggests clear classification of participants into that cluster.As a sensitivity analysis, LCGA was repeated using participants completing the chest pain and SoB items on at least 2 monthly questionnaires. A further sensitivity analysis used multiple imputation to impute clusters for all baseline CVD respondents, with 50 imputations, and using baseline age, gender, BMI, anxiety, depression, PCS score, number of pain sites elsewhere and baseline chest pain, SoB and HF diagnosis in the imputation. All analysis was done using Stata V.14, Mplus V.7.3 and MLwiN V.2.35.Two thousand and eight hundred and fiftyeight patients with CVD were mailed the baseline questionnaire, of which 1696 (59%) responded. Six hundred and sixty-one (39%) baseline responders answered the chest pain and SoB items on between 5 and 10 monthly questionnaires and were included in the main analyses reported here. Compared with all other baseline responders, those in the analysis were younger (mean difference 2.3 years), had a higher proportion of males (68% vs 62%) and had a slightly lower prevalence of chest pain (42% vs 44%) and SoB (54% vs 58%) at baseline .During the 10-month follow-up period, prevalence of chest pain during activity in all 4 weeks ranged from 11% to 13% by month and that of chest pain for 1–3 weeks from 23% to 28%. Monthly prevalence of SoB during activity in all 4 weeks ranged from 21% to 26% and SoB for 1–3 weeks from 34% to 37%.Unadjusted analysis showed increasing number of pain sites elsewhere, being anxious or depressed and having a worse PCS score were associated with an increase in risk of reporting chest pain in all 4 weeks in a month.After adjustment for all covariates, an increasing number of pain sites (relative risk ratio (RRR) for 4+ vs none: 4.03, 95% CI 1.64 to 9.91) and being anxious or depressed  were associated with reporting chest pain in all 4 weeks in the previous month . The intUnadjusted analysis showed more pain sites elsewhere, being anxious or depressed, obesity, female gender and having a worse PCS score were associated with an increase in risk of reporting SoB during activity in all 4 weeks in the last month.After adjustment for all covariates, increasing number of pain sites , being anxious or depressed  and obesity  were associated with increased risk of reporting SoB in each of the previous 4 weeks, as were female gender and being over 80 years of age. There were no statistically significant interactions with time .Sensitivity analyses including those responding on at least 2 monthly questionnaires (n=777) and using multiple imputation did not change the findings  generally reported no chest pain or SoB symptoms (with monthly probability 0.95 and above) in all the monthly questionnaires. Across clusters, in those reporting symptoms, SoB was more common than chest pain. One cluster of patients reported infrequent breathlessness symptoms , another cluster of patients reported occasional breathlessness symptoms  and a third cluster of patients reported persistent breathlessness symptoms , but people in these three clusters rarely reported chest pain. The smallest cluster reported occasional chest pain, but rarely reported SoB . Two clusters reported occasional  or frequent  pain alongside breathlessness. The most severe group of patients reported persistent SoB and pain over the 10 months, that is, reported SoB and pain for all 4 weeks in all monthly questionnaires .Patients allocated to the largest cluster  and worse physical health in general . Levels Sensitivity analysis, including respondents with at least 2 monthly responses, showed a similar distribution of participants across clusters  influence the experience of both occasional and persistent chest pain and SoB during activity, and that eight distinct symptom trajectories are apparent, with breathlessness symptoms more common than chest pain.Three of our identified clusters consisted of patients with stable conditions. The most common cluster (containing a quarter of our sample) reported no symptoms every month. By contrast, one cluster reported persistent chest pain and SoB every month, and another reported persistent SoB without chest pain every month. Symptoms of patients in the remaining clusters fluctuated more. We did not observe a cluster who improved or worsened over the 10 months, which may reflect the prevalent rather than incident nature of the cohort.Though chest pain and SoB may be considered a distinctive symptom of acute CVD conditions, such as myocardial infarction, a quarter of our prevalent CVD sample did not experience these symptoms at all, similar to a study of community recruited patients with HF from the UK.Patients with CVD who were obese at baseline were more likely to experience SoB compared with those of normal weight. This in line with other research and also demonstrates potential to improve this common CVD symptom. Bernhardt and Babbet al reported that improving (or diminishing) SoB after 2 years depended on whether pain resolved or diminished respectively.We have shown that chest pain and SoB are associated with anxiety and depression and pain elsewhere, and addressing these characteristics may benefit both symptoms. Clark Our clusters provide distinct patterns of symptom experience over time within a CVD population. Three-quarters of patients with CVD experienced either SoB or chest pain; however, approximately a third of our sample (35%) reported SoB only, either infrequently (14%), occasionally (13%) or persistently 8%). These may represent a cluster of patients at greater risk of poor outcomes. In a large sample of US participants with coronary artery disease at baseline, the mortality rates were twice as high in patients with SoB compared with those with other symptoms and four times greater than in those with no symptoms at presentation.%. These The strength of our study lies in its prospective cohort design that has used a large CVD sample from primary care to gain an insight into the monthly experience of chest pain and SoB symptom in this sample. This study was conducted within a UK primary care setting using monthly surveys from patients with a diagnosis of CVD, identified through electronic health records from 10 general practices. Since these patients were identified from general practices across North Staffordshire, Stoke-on-Trent and Cheshire, they represent a sample generalisable to the UK primary care population.29This is the first research to examine monthly trajectories of these symptoms in CVD patients.There are several limitations to our work. First, due to the prospective nature of our research, there was attrition during the follow-up period. Those in the monthly analysis were slightly younger and more likely to be male than all those responding at baseline. Related to attrition, our use of multiple imputation may be limited as we are unable to determine if missing values are truly missing at random. In the monthly questionnaire, our definitions of chest pain and SoB were based on a single question for each. Though using a short monthly questionnaire improved the month-on-month response rates, such a simple definition may limit the accuracy of patient responses. The questions related to chest pain and SoB that occurred during activity; however, it is possible that the symptoms may be non-cardiovascular in origin. We also did not identify the number or duration of symptom episodes other than in how many weeks they had occurred in the last month. However, no matter the specific cause of the chest pain or SoB, patients with CVD are experiencing these symptoms, and therefore these need to be addressed.Several modifiable patient characteristics  are associated with the experience of both occasional and weekly chest pain and SoB during activity. Future interventions to improve CVD symptom experience may wish to target these covariates. By identifying trajectories of symptoms over time, care may be better tailored to improve outcomes in those patients with CVD at greatest risk of worse symptoms and disease progression.


Postoperative pain after laparoscopic cholecystectomy can be severe. Despite multimodal analgesia regimes, administration of high doses of opioids is often necessary. This can further lead to several adverse effects such as drowsiness and respiratory impairment as well as postoperative nausea and vomiting. This will hinder early mobilization and discharge of the patient from the day surgery setting and is suboptimal in an Early Recovery after Surgery setting. The ultrasound-guided Erector Spinae Plane (ESP) block is a novel truncal interfascial block technique providing analgesia of the thoracic or abdominal segmental innervation depending on the level of administration. Local anesthetic penetrates anteriorly presumably through the costotransverse foramina to the paravertebral space. We demonstrate the analgesic efficacy of the ESP block in a case series of three patients scheduled for ambulatory laparoscopic cholecystectomy. Laparoscopic cholecystectomy is associated with moderate to severe pain despite all currently available multimodal analgesic regimes –3. The uWritten informed consent for publication was obtained from all three patients. There was no need for approval by the Central Denmark Region Committees on Biomedical Research Ethics.2 presented for elective ambulatory laparoscopic cholecystectomy. He was diagnosed with obstructive sleep apnea treated with nightly continuous positive airway pressure (CPAP) therapy. He was otherwise healthy and did not take any medication. A bilateral ESP block was performed just prior to surgery. The patient was sitting up and the level of the T7 transverse process was located just 3 cm laterally from the midline using a 15–6 MHz linear ultrasound probe  oriented sagittally  with a pressure of 12 mmHg. At the end of the uncomplicated surgical procedure the laparoscopic port sites were infiltrated with 20 mL of ropivacaine 0.2%, and CO2 was evacuated. Extubation was uneventful but in the postanesthesia care unit (PACU), the patient was drowsy and complained about dyspnea, which was suspected to be caused by a combination of mild intermittent airway obstruction, anxiety, and pain. It was thus treated with a nasal airway, fentanyl 50 μg IV, and morphine 10 mg orally. Once fully awake, the patient denied that the incident was due to pain but reported that he had been anxious because of dyspnea. Numerical rating scale (NRS) was 2/10 and remained below 3/10 for the rest of his stay in the PACU and he did not receive any further medication. He was discharged to home 2 hours and 56 min after arriving in the PACU.A 42-year-old man with a body mass index (BMI) of 35.8 kg/mgittally . The cro2) was scheduled for ambulatory laparoscopic cholecystectomy. She did not present any comorbidities besides being a smoker (40 pack years). The ESP block was performed 45 min preoperatively at the level of the T7 transverse process as described above under mild sedation with fentanyl 50 μg IV. She received standard premedication with paracetamol and ibuprofen. Induction was performed with propofol 190 mg and remifentanil 250 μg and maintained with propofol 70 μg/kg/min and remifentanil 0.3 μg/kg/min. Intubation and extubation were uneventful. Intraoperative medication was similar to patient 1. The first NRS in the PACU was 2/10 and subsequent scores were 0–2/10. Morphine 10 mg was administered orally due to earlier standard protocols, although the patient did not have any pain complaints. The patient was discharged to home from the PACU 3 hours and 32 min after arrival.A 49-year-old woman (BMI 28.4 kg/m2) also presented for ambulatory laparoscopic cholecystectomy. Her only comorbidities were depression and anxiety, which were well controlled with oral nortriptyline and pregabalin. Premedication with paracetamol and ibuprofen was similar to the other two cases described above. The ESP block was carried out 45 min preoperatively at the level of the T7 transverse process similar to patients 1 and 2. Induction was achieved with propofol 140 mg and remifentanil 250 μg and maintained with propofol 71 μg/kg/min and remifentanil 0.13 μg/kg/min. She also received intraoperative dexamethasone, droperidol, ondansetron, and port site infiltration. Fentanyl 100 μg was administered intraoperatively. After uncomplicated surgery and extubation the patient was transferred to the PACU. In the PACU the patient only complained of minor pain (NRS < 3/10). She received fentanyl 50 μg, and at discharge to home 2 hours and 1 min later her NRS score was 0/10.A 65-year-old woman  diaphragmatic muscle fiber stretching with tearing of muscular blood vessels and traction on nerve fibers, and (3) retained residual pockets of gas in the abdominal cavity [Pain can be severe after laparoscopic cholecystectomy , 3. Thisl cavity . About 3l cavity . It is ul cavity . The mecl cavity .For comparison, regarding how the normal patient without a block does at our institution, we have carried out a survey from the first 50 laparoscopic cholecystectomies at our department in 2016 (yet unpublished data) with multimodal analgesia . Immediately after awakening, about half of patients (56%) had minor pain (NRS 0–3) and about half of patients (44%) had moderate to severe pain (NRS 4–10). About one-fourth of the patients (24%) just had minor pain (NRS 0–3) during the entire PACU stay, whereas about three-fourths of the patients (76%) at some point had moderate to severe pain (NRS 4–10). Interestingly, only half of the patients who initially just had minor pain (NRS 0–3) continued having minor pain, whereas the other half of the patients with initial minor pain experienced stronger pain later during the PACU stay. Another point of interest is that 1 out of 7 patients 14%) at some point in the PACU had excruciating pain (NRS 8–10), which corresponds to earlier reported numbers [% at someOpioid requirements at home after ambulatory laparoscopic cholecystectomy are variable . AccordiPONV has previously been described to exist in about 10% of patients after laparoscopic cholecystectomy with multimodal anesthesia , 16. Pai2 gas and reduce postoperative overall pain [The concept of “fast-track surgery” or Enhanced Recovery after Surgery (ERAS) programs applied on laparoscopic cholecystectomy requires multimodal analgesia including paracetamol, NSAIDs and dexamethasone in addition to opioids as rescue medication –3, 18. Pall pain , 21. Thiall pain , 22. TAPall pain .Since its first description in 2016 numerous case reports about the ESP block have been described for thoracic and abdominal procedures including thoracic neuropathic pain , 6, ventUnlike earlier beliefs, the fascial planes in the paravertebral region may not be bound true compartments . Local aThere are several unanswered questions to address. Firstly, the ESP block has so far only been described in case reports, and the promising results must be validated in future randomized clinical trials. Secondly, the optimal time for block placement should be considered. In general, this is the best achieved preoperatively in the awake patient. About three-fourths of the patients experience moderate to severe pain some time during the postoperative period. A minority of the patients experience excruciating pain. Thirdly, optimal volume and concentration of local anesthetic are unknown. Previous authors have mainly used ropivacaine 0.5% 20 mL providing analgesia for about 20 hours reducing opioid consumption to about one-third . A similThe three reported cases illustrate the efficacy of the ESP block for somatic and visceral pain relief after upper abdominal laparoscopic cholecystectomy. The results must be validated in future randomized controlled trials.