Evidence from the past 20 years has highlighted that acute pain is not managed well in the emergency setting, in particular with children. Inadequate management of pain can result in long-term changes in both physical and mental health. This service evaluation aimed to determine how paediatric pain is assessed and managed by ambulance clinicians in a large region in England.This retrospective service evaluation analysed electronic patient record (ePR) data routinely collected between September and December 2018. All paediatric patients (< 18 years of age) with pain documented narratively, or a pain score of ≥ 1/10, were included. The primary outcome measure was the proportion of patients with severe pain (defined as a pain score of ≥ 7/10) who achieve effective pain management (reduction in pain score of ≥ 2/10).A total of 2801 paediatric patients who had documented pain were included in the analysis and the median age of patients was three years . Most had a medical cause of pain , and analgesia was administered by the ambulance crew in 403/2801 (14.4%) patients. Multiple pain scores were recorded for 667 patients. Effective pain management was achieved in 233/271 (86%) patients in moderate pain and 204/210 (97.1%) patients in severe pain. However, of the 437 children in moderate to severe pain who achieved effective pain management, 381 (87%) received no analgesia.Children in severe pain received effective pain management, despite the majority not receiving any analgesia. This should be investigated further since non-pharmacological methods of analgesia are unlikely to explain a reduction of this magnitude. Ambulance staff need to be encouraged to record a pain score promptly after arriving on scene and ensure it is repeated. Pain score should be documented as part of the physiological observations and not in the free text of ePRs to ensure that it is identified during audits. Relieving pain is an important role of healthcare professionals . HoweverThere are numerous studies relating to the out-of-hospital management of paediatric pain that suggest it is inadequate, whether due to inadequate pain assessment and/or analgesic administration . There iThis service evaluation aimed to determine how paediatric pain is assessed and managed by Yorkshire Ambulance Service NHS Trust (YAS).A retrospective service evaluation analysing routine data collected between September and December 2018 was undertaken, to determine how paediatric pain is assessed and managed by YAS.YAS provides 24-hour emergency and healthcare services for the county of Yorkshire, in England. The county has a population of approximately 5 million, spread over almost 6000 square miles of varied terrain, including isolated moors and dales, coastline and urban areas. YAS operates 62 ambulance stations, and in 2017–2018 received 946,881 emergency calls which resulted in 778,639 attendances by YAS staff. Approximately 5% of these involved paediatric patients.The primary outcome measure is the proportion of patients with severe pain (defined as a pain score of 7/10 or greater) who have a reduction in pain score of 2 or more.Secondary outcomes include:proportion of paediatric patients with documented pain who have analgesia administered;proportion of paediatric patients where pain is described in the text of the ePR without a pain score being recorded;proportion of paediatric patients who have more than one pain score recorded;median time from arrival to pain scoring and analgesic administration;frequency of analgesic administration to paediatric patients stratified by pain severity and presumed cause of pain;frequency of specific pain score tool use in paediatric patients, e.g. Wong-Baker or Face, Legs, Activity, Cry, Consolability (FLACC) scales; andfrequency of attendance of emergency medical technician (EMT) 2/paramedic in cases of severe paediatric pain.All electronic patient records (ePRs) created between 1 September 2018 and 31 December 2018 which matched the following inclusion criteria were requested from the YAS business intelligence team:accessed the ambulance service via 999/111;received a face-to-face assessment with a clinician;less than 18 years of age at time of call; andhad at least one pain score of 1/10 or greater recorded, or had documented pain recorded in the free text of the ePR.Cases were excluded if the working impression code was: ‘no illness or injury’. The following data items were extracted from the ePRs:patient age;initial and subsequent pain scores and the time they were recorded;attending ambulance staff skill level, e.g. paramedic/EMT;administered medications and the time they were recorded;time spent with patient out-of-hospital ; andpresenting complaint;history of complaint;initial presentation;working impression;on examination;diagram notes;care plan;transported;non-transport reason; andadvice text.the following free text ePR fields:A descriptive analysis was conducted using custom computer code created within the statistics package, R . This coBetween 1 September 2018 and 31 December 2018, there were 9748 ePRs created for patients aged 0–17 years who had received a face-to-face assessment by YAS staff following a 999/111 call. Once 52 cases with a working impression of ‘no illness or injury’ were excluded, 2801 patients remained who had documented pain, either recorded in the free text of the ePR, or as a pain score of 1/10 or greater .The distribution of paediatric patients with pain is bimodal, with the highest number of patients aged under 4 years and over 15 years of age .® scale is presented to the ambulance clinician to assess pain. In this dataset, 1915 (68.4%) paediatric patients were under the age of eight, and 1641 had at least one pain score recorded.At least one pain score was documented in 2217/2801 (79.2%) of paediatric patients, with 667/2801 (23.8%) having more than one pain score documented. There were 109/2801 (3.9%) cases where it was documented that a pain score could not be recorded, and there were 475/2801 (17%) cases where pain was documented in the free text but no pain score recorded. In total, 403/2801 (14.4%) patients in pain received analgesia from the crew, with 268/2217 (12.1%) patients receiving analgesia having had a pain score recorded. There were few documented cases of Wong-Baker/FLACC assessment tool use, with 12 documented cases of their use in the free text of the ePR. However, by default, for paediatric patients under the age of eight years, the Wong-Baker FACESThe median time from arrival to first pain score was 12 minutes (interquartile range (IQR), 6–25) and from arrival to analgesia administration, 19 minutes . A paramedic or EMT was on scene in 2270/2801 (81%) of cases, with a paramedic on scene, and thus all analgesic options available, in 1952/2801 (69.7%) of cases.The most commonly administered drug was paracetamol (n = 310), followed by entonox (n = 81) and ibuprofen (n = 78). The most common combination of analgesic drugs was paracetamol and entonox (n = 30), and paracetamol and ibuprofen n = 19, . A totalFor the subgroup of patients who had two pain scores recorded (n = 667), there was a pain score reduction of two points or more in 233/271 (86%) patients with moderate pain and 204/210 (97.1%) patients in severe pain. The majority of patients who received no analgesia also appeared to demonstrate high levels of pain score reduction .Of the 2801 paediatric patients with pain reported, 475 (17%) did not have a numerical pain score recorded as part of the physiological observation section of the ePR. However, 81/475 (17%) records contained at least one pain score in the free text portion of the ePR, which would not typically be picked up in an audit. If these pain scores are added to the total number of patients who have at least one pain score (or a documented reason why one could not be obtained), this would total 2407/2801 (85.9%). However, there were 105 drug administrations with no pain score recorded, but pain documented in the free text of the record .Since a definitive diagnosis is not always possible in the out-of-hospital environment, ambulance staff typically record a single working impression from a pre-defined list. While not clearly defined, a working impression could be considered to be the clinician’s current hypothesis as to the likely cause or immediate healthcare need that explains the patient’s presentation, from which the management plan is based. The top 20 working impressions for patients with recorded pain of medical impression can be seen in There were 414 paediatric patients with a traumatic cause to their pain. In this evaluation of 2801 paediatric patients who had an ePR completed by a YAS clinician between 1 September 2018 and 31 December 2018 and had documented pain, 403/2801 (14.4%) had analgesia administered by ambulance staff and 2217/2801 (79.2%) had at least one pain score recorded. If the ‘unable to record a pain score’ (UTR) fields and documented pain scores in the free text are included, this total rises to 2407/2801 (85.9%).Making direct comparisons with other literature is difficult, due to varying inclusion criteria for patient age and presenting complaint. One of two published studies conducted in UK NHS ambulance services is a service evaluation conducted by In Ireland, Further afield, In this study, the median time from arrival on scene to initial pain score was 19 minutes (IQR 7–31 minutes) for severe pain, which was longer than that for mild and moderate pain. It is not clear why this should be the case, although perhaps it reflects the severity of injury and illness, and other treatment took priority initially. This view might be substantiated by the higher median time in the trauma group. However, once a pain score had been recorded, time to analgesia was prompt in cases of severe pain.There were 105 cases where a pain score was not recorded and it was not possible to determine the reasons for the absence of a score. Difficulty in obtaining pain scores in children has been described in other studies , and it ® pain rating scale and FLACC pain assessment tool are in widespread use, they have not been validated for use out-of-hospital by ambulance clinicians. It may not be appropriate to consider scores calculated by FACES® as equivalent to the numerical rating scale (NRS), except in older children .While the Wong-Baker FACESchildren . In addi® and FLACC scores in younger children.While FLACC is allocated a score from 0 to 10 in single increments, in the same way as the NRS, it is not clear whether automatically transposing a FLACC score to an NRS is appropriate. Studies validating the FLACC score are inconclusive as to its ability to discriminate pain in younger children. For example, while There were few documented cases of specified FLACC or Wong-Baker pain scale use in this evaluation, however since it is the default pain scoring option for all patients under the age of eight, it is likely that a high proportion of patients did have their pain scored using this scale.This study found a low rate of analgesia administration (14.4%) despite a high amount of pain scoring (85.9%). This is a significant finding compared to the literature. The most commonly administered analgesic drugs in this evaluation were paracetamol, entonox and ibuprofen, which is similar to that reported by However, non-pharmacological methods of pain relief, such as distraction, or cooling burns, were not extracted from the ePRs, but it is unlikely that such alternative methods of pain relief completely explain the reductions in pain score seen for the large number of patients that had no analgesia being administered.This evaluation is a retrospective review of routine electronic records, which represents approximately 68% of all paediatric incidents that occurred during the time of the evaluation. The low number of patients with multiple pain scores, particularly those in severe pain, makes it difficult to generalise. It also relies on clinicians accurately recording what they did and when, including documenting when drug administration was inappropriate. This is particularly relevant for infants, since analgesic options for paramedics are limited. In addition, over 50% of paediatric patients in this evaluation were under the age of three years, and are in a difficult group to assess and administer analgesia to.Due to the number of ePRs, it was necessary to automatically process the free text using a bespoke algorithm. However, it is possible that this method included or excluded patients inappropriately. On the positive side, it did enable identification of paediatric patients who did not have pain scores identified, a group that has been missed by studies that have a pain score of 1/10 or greater as an inclusion criterion.Pain assessment in this evaluation is consistent with figures published elsewhere, although the frequency of analgesic administration appears to be significantly lower, especially in medical patients. Children in severe pain received effective pain management, despite the majority not receiving any analgesia. This should be investigated further since non-pharmacological methods of analgesia are unlikely to explain a reduction of this magnitude. Ambulance staff need to be encouraged to record a pain score promptly after arriving on scene and ensure it is repeated. Pain scores should be documented as part of the physiological observations and not in the free text of ePRs to ensure that they are identified during audits.None declared.Not required.None.


Nutcracker syndrome is a rare disorder caused by compression of the left renal vein, usually between the aorta and the superior mesenteric artery. It typically presents with left-sided abdominal pain and hematuria. Left renal vein transposition is the most commonly employed surgical technique to alleviate the compression.A 22-year-old Caucasian man with a known diagnosis of nutcracker syndrome had undergone left renal vein transposition 1 year before presentation without any subsequent pain relief. In addition, his surgery was complicated by massive blood loss and a 1-week-long stay in an intensive care unit (ICU); as such, he was not amenable to further surgical intervention or stenting to treat his underlying pathology. His symptoms included constant sharp left-sided flank, perineal, and testicular pain. A series of ganglion impar blocks were performed every 3–4 months over the course of 5 years with substantial pain relief achieved.Our case report highlights a treatment option that has not yet been described for patients with pain secondary to nutcracker syndrome refractory to surgical intervention. Nutcracker syndrome is a disorder caused by compression of the left renal vein. The vein is usually compressed between the aorta and the superior mesenteric artery (SMA), known as “anterior nutcracker”; an anatomic variant of the left renal vein may course between the aorta and vertebra, where it can also be compressed, known as “posterior nutcracker” . ProposeA 22-year-old Caucasian man with a medical history of epilepsy, nephrolithiasis, and nutcracker syndrome presented with abdominal and perineal pain. The patient’s family history was negative for nutcracker syndrome and pelvic congestion syndrome. The pain was ongoing for approximately 3 years before the initial consultation, and a left renal vein transposition was undertaken 1 year before initial consultation, without any improvement in his symptoms . The block included 15 ml of 0.25% bupivacaine with 15 mg of dexamethasone. As a result, the patient underwent serial ganglion impar blocks over the course of 5 years, which significantly improved his symptoms . Some residual mild left flank pain persisted at times. Ganglion impar neurolysis was proposed; however, the patient declined for two reasons. Primarily, he was fearful of the possibility of perineal and testicular dysesthesias and hyperesthesias. Secondarily, because pain relief from neurolysis generally lasts no more than 6 months, he did not think the benefits outweighed the risks, considering that he was already benefiting from long-lasting pain relief from his current intervention. Although ganglion impar blocks were relieving his symptoms well, the patient wanted to explore more permanent options after approximately 2 years of consultation. For this reason, an intrathecal morphine trial was undertaken, but he was dissatisfied because of excessive pruritus and constipation and only a 60% reduction in pain. Later, a dorsal root ganglion trial was proposed; however, the patient had hesitation concerning permanent implantation of a device at that time. No adverse or unanticipated events have occurred as a result of his ganglion impar blocks.Treatment of nutcracker syndrome varies, depending on the patient’s age and severity of symptoms. Pediatric patients have a higher rate of spontaneous remission, and, as such, patients younger than 18 are usually surveilled for 2 years versus 6 months in adults. Seventy-five percent of pediatric patients will have complete resolution of their hematuria in this time period . This isLeft renal vein transposition is the most commonly employed surgical technique and is currently considered the gold standard on the basis of good outcomes and relatively low complication rates . It invoThe decision to undergo ganglion impar blocks rather than repeat celiac plexus neurolysis stemmed from our patient’s response to the interventions. The majority of his pain was in the testicular and perineal area, with only a minority in the left flank. As a result, our patient experienced more pain relief with ganglion impar blocks. However, the minority of pain not covered was usually in his left flank as a result. The patient was aware that risks of repeated steroid injections include weight gain, insulin resistance, and increased blood pressure; however, he felt that the benefits outweighed the risks. In addition, the patient was aware that his pathology persisted despite his pain relief. Overall, the patient has been satisfied with his results thus far.We report the successful treatment of abdominal, perineal, and testicular pain in a 22-year-old man with nutcracker syndrome. Our case report highlights a treatment option that has not yet been described for patients with pain secondary to nutcracker syndrome refractory to surgical intervention.


The prevalence of cancer pain is too high. There is a need for improvement of pain management in cancer care. The aim of this study was to explore whether the use of the multidimensional pain assessment questionnaire Brief Pain Inventory (BPI) could improve pain relief in hospitalized patients with cancer.A controlled intervention study was performed at two hospitals in western Sweden, 264 patients were included, 132 formed a control group and 132 an intervention group. All participants completed the BPI and the Edmonton Symptom Assessment Scale (ESAS) at baseline. Only the researcher had access to questionnaires from the control group. The completed forms from the intervention group were presented to the patients’ care team. A follow-up took place after 2–5 days when patients in both groups rated the scales a second time.In the intervention group, significant differences in all measured items of the BPI were found at follow-up compared with baseline. Symptoms rated with the ESAS also decreased significantly, except shortness of breath. At follow-up, a significant increase in regular use of paracetamol, anti-neuropathic pain drugs and opioids was found, as well as elevated doses of fixed-schedule opioids. In the control group, differences between baseline and follow-up were significant regarding average pain and worst pain over the past 24 h.Presenting the patient-reported BPI to the care team helped them to focus on patients’ pain, identify pain mechanisms and adjust analgesics accordingly. A possible explanation for the results is changes in the medication prescribed. The prevalence of cancer pain is still far too high and has not improved significantly over the last decade , as compPain in cancer patients is caused by the direct effect of the tumour or may be related to side effects of chemotherapy, radiation treatment and therapeutic procedures . The mosEvidence-based guidelines describing assessment and treatment of nociceptive, neuropathic and breakthrough pain are available , 13. TeaThe Brief Pain Inventory (BPI) is a patient-reported questionnaire, which is widely used for measuring pain intensity and how pain interferes with everyday life such as walking, general activity and work (activity dimension), sleep, mood, relations with others and enjoyment of life (affective dimension) –16. TherThe aim of this study was to explore whether the use of the multidimensional pain assessment questionnaire BPI could improve pain relief in hospitalized patients with cancer.A controlled intervention study was performed at a university hospital and a county hospital in western Sweden. A total of 264 patients were included.The patients included at the university hospital were recruited from the radiotherapy, oncology, haematology, pulmonary and palliative care units. At the county hospital, patients from the surgery, urology, medicine, pulmonary, head and neck and gynaecology units were included. The study was conducted over 4 months in 2016 and 4 months in 2017 at the county hospital and over 3 months in 2017 and 1 month in 2018 at the university hospital.The inclusion criteria were inpatients who had been diagnosed with cancer, age ≥ 18 years, ability to understand and speak Swedish, a pain rating of moderate or higher (≥ 4) on a 0–10 numeric rating scale (NRS) and agreeing to participate in the study. Exclusion criteria were having undergone surgery during the previous 3 weeks, cognitive disability and critical illness.The control group comprised the first half of the patients recruited from each hospital. They received their usual treatment.The second half of patients at both hospitals constituted the intervention group. The reason was that we did not want staff to start using the BPI on all patients before the data collection was finished.Participants in the intervention group completed the BPI multidimensional pain questionnaire and the Edmonton Symptom Assessment scale (ESAS)  at baselParticipants in the control group also completed the BPI and ESAS at baseline. Only the researchers had access to the control group questionnaires.-up the medical records were scrutinized for analgesic prescriptions.A follow-up took place after 2–5 days when patients in both the control group and the intervention group rated the BPI and ESAS a second time. Patients who had been discharged from hospital were contacted by phone. At followDemographic characteristics, i.e. age and sex, and clinical characteristics such as main diagnosis, documentation of pain and prescribed analgesic treatment were derived from the medical records. A structured, verbally administered questionnaire was used to obtain information from the patients, including the questions “In what year did you receive your diagnosis?”, “Have you undergone surgery? Radiation? Chemotherapy? Curative treatment?” and “Are you registered with a palliative consultation team or an advanced home care team?” If a patient was unable to answer a question, the nurse who cared for her/him was asked to provide the information.Two additional questions were posed directly to the patient: “Have you previously used a pain rating scale during this hospital stay?” and “What do you consider effective for relieving pain?”Pain during the previous 24 h was assessed using the BPI, which has been found to have good reliability and validity for measuring cancer pain , 18. TheThe ESAS was used to obtain information about other symptoms such as fatigue, nausea, downheartedness, tiredness, anxiety, drowsiness, loss of appetite, shortness of breath and reduced QoL. In this study, two items about pain were removed because they are covered by the BPI. The ESAS ranges from 0 = no influence to 10 = maximum influence  and has A total of 264 patients were included, 132  in the control group and 132  in the intervention group. Assuming an expected difference in pain intensity of 10% in the BPI, 65 individuals in each group are required to obtain 80% power at a significance level of 0.05; thus 130 patients from each hospital were necessary.Statistical analyses were carried out with IBM SPSS Statistics 21  using the Wilcoxon signed-rank, chi-square or McNemar test. Descriptive statistics were performed for all items in the BPI and ESAS. The responses from the control and the intervention group at baseline and follow-up were compared within each group, and outcome analyses were conducted. The baseline responses to the BPI items were compared between the control and the intervention group. Data from the medical records including documented pain and pain rating were analysed.Analgesic prescriptions at baseline and follow-up for both groups were compared within each group. The completed BPI was analysed to identify nociceptive, neuropathic or mixed pain based on the patients’ descriptions of the pain characteristics , 13 and The patients were informed about the study orally and in writing. Participants provided both oral and written consent. All patients were informed that they would be contacted by phone to perform the follow-up assessment if they had been discharged from hospital, to which all consented orally. The study was approved by the Regional Ethics Board in Lund, Sweden .The study included 155 women (58.7%) and 109 men (41.3%), median age 69 (range 18–92) years. The most common diagnoses were gastrointestinal cancer (25.8%), lung cancer (15.5%) and head and neck cancer (13.6%). Patient characteristics are presented in Table Among eligible patients, a total of seven declined to participate. At baseline, 132 patients participated in the control group and 132 in the intervention group. Figure Notes in the medical records concerning pain were available for 187 (70.8%) of the 264 participants at baseline. Documented pain assessment over the past 24 h was available in the medical records for 81 patients (30.7%). Ninety-nine patients (37.7%) stated that they had used the pain assessment scale previously during their hospital stay.n = 264), 82% stated that analgesics provided pain relief and 26.5% reported that a change in position alleviated pain. Heat (12.9%), transcutaneous electrical nerve stimulation (TENS), massage and physical activity were also described as providing pain relief (12.5%). Furthermore, a positive environment, distraction and good treatment from the staff further provided relief (18.5%). Patients with ongoing radiation therapy for head and neck cancer stated that rinsing the mouth with water, saline solution or local anaesthesia (mouthwash) provided pain relief (9.4%) . In the control group, significant differences were found regarding worst pain over the past 24 h (p = 0.020) and average pain (p = 0.022) (Table n = 264).Significant differences in all items on the BPI were found in the intervention group at follow-up compared with baseline (p = 0.844); in all,153 patients (63%) experienced mixed pain, a combination of nociceptive and neuropathic pain, 34% reported only nociceptive pain and 3% experienced exclusively neuropathic pain. No significant difference was seen between the groups concerning pain site (p = 0.264); 60 patients (25%) had multifocal pain in three or more locations; 75% reported one or two locations. Several patients with ongoing radiation therapy had inflammatory components to their pain, such as erythema, ulcers, tenderness and swelling at the radiation site.No significant differences in pain pathophysiology were seen between the control and the intervention group (p = 0.008) at follow-up but a decrease in use of paracetamol as needed (p = 0.035), as well as a significant increase in strong opioids at a fixed schedule (p = 0.012). The addition of medications for neuropathic pain had increased at follow-up in the intervention group (p = 0.039) (Table p = 0.021) at follow-up (not shown in the Table).No significant differences regarding pain medication prescriptions were seen at follow-up in the control group. In the intervention group there was a significant increase in prescribed regular use of paracetamol  in our study reported that analgesics provided relief for their basic pain or breakthrough pain. The participants also used non-pharmacological methods to alleviate pain such as a changing position, heat, TENS, massage and physical activity. A friendly treatment, socializing with others, a pleasant environment, beautiful things and nature were sources of distraction and relief. Pain is a multidimensional experience , which mIn the present study, significant differences between baseline (NRS 7.4) and follow-up (NRS 5.6) were seen in perceived worst pain over the past 24 h in the intervention group, while the negative impact of pain on other parameters also showed a significant decrease. The results of this study suggest an improvement for patients who were given the opportunity to communicate their pain to the care team through the BPI questionnaire; their pain was more adequately addressed, thereby providing a basis for initiating pain-relieving measures. Pain intensity ≥ 5 among cancer patients has been shown to significantly impact QoL by interfering with daily activities, mood, sleep, enjoyment and relationships .Our findings are consistent with others showing that pain intensity can decrease when medications are adjusted by an experienced pain management physician , when paIn this study, 34% of patients had nociceptive pain, while 63% had mixed pain and 3% neuropathic pain only. Other studies have reported that neuropathic pain occurs in 44–67% of hospitalized cancer patients –35. We aAt follow-up, we found a significant increase in regular use of paracetamol and strong opioids, in addition to medications for neuropathic pain and elevated doses of fixed-schedule opioids in the intervention group, which we interpret as one explanation for the significant decrease in pain levels. In the intervention group, 25% were prescribed analgesics for neuropathic pain at follow-up. This is a higher percentage than the 10% and 8% reported elsewhere , 36 but We conclude that in many patients, improved pain management can be achieved through relatively simple adjustment of analgesics. It was further noticed that other administration methods, such as regional infusion, nerve block, intrathecal or epidural administration or intravenous/subcutaneous patient-controlled analgesia (PCA), could also have been tried in some of our patients with severe pain , 12, 13., other studies on cancer patients have also demonstrated a large influence of these items [The ESAS scores showed significant improvement in the intervention group for all measured parameters except shortness of breath. This can be interpreted as meaning that decreased pain has a beneficial effect on other symptoms in cancer patients. Of the symptoms assessed by the ESAS before the intervention, fatigue and QoL averaged about 6 on a scale of 0–10se items , 39, 40.se items . These ase items . One stuse items . The majLimitations of this study are that there were differences in the time interval between baseline and follow-up, because the researchers were unable to follow up all participants at the same interval. Furthermore, some diagnostic groups were quite small; more participants within each diagnostic group could have provided additional information. Strengths in this study are that we used patient-reported data, that it is a relatively large sample and that the study was performed in two hospitals, of different characteristics, i.e. a university hospital and a county hospital.In conclusion, the present study provides valuable information about the effect of a multidimensional pain assessment intervention on cancer pain and other symptoms in hospitalized patients with cancer. The study demonstrates that use of the BPI can highlight and contribute to cancer pain relief and that decreased pain can have a positive effect on other pain-related dimensions and symptoms. This highlights the importance of healthcare staff treating pain in a professional way, identifying pain mechanisms, using guidelines and taking a team approach.


Studies show significant alterations in insular cortical thickness in patients with somatoform pain disorder (SPD). Additionally, associations between childhood maltreatment and morphometric alterations in insular cortex have been observed. Since patients with SPD often report about adverse childhood experiences, we were interested in the interrelationship of exposure to childhood maltreatment and insular cortical thickness in patients with SPD.p < .05). Then we performed a secondary analysis to detect differences in cortical thickness levels in the insular cortex between both groups. For further analysis of differences in insular cortical thickness we used gender, age, depressive symptoms [Patient Health Questionnaire (PHQ)-9], and whole brain cortical thickness as nuisance covariates. Subsequently we explored associations between insular cortical thickness, symptom severity (PHQ-15) and past experiences of childhood maltreatment (CTQ) in both groups.Fifteen adult patients with SPD  and thirteen healthy adult controls underwent T1-weighted MR brain imaging. In the voxel-based morphometry (VBM) analysis we compared whole brain cortical thickness between patients and controls using a Student’s two-sampled t-test  13 (anterior part of the insular cortex), whereas whole brain cortical thickness did not differ between groups. The between-group difference in the identified insular subregion of right BA 13 was not diminished by any of the covariates. This implies that the reduction in cortical thickness in the identified insular subregion might be due to a specific group effect. The effect sizes indicate that the group of patients experienced more childhood maltreatment than the control group. Nonetheless, significant correlations of insular cortical thickness with symptom severity and childhood maltreatment in the total collective could not be demonstrated for the group of patients.Our data suggest that alterations in the identified insular subregion of right BA 13 are associated with somatoform pain, independent of gender, age, or coincident depression levels. To identify significant associations of insular cortical thickness and experiences of childhood maltreatment in patients with SPD investigations within larger samples are highly recommended. Patients with chronic somatoform pain disorder (SPD) suffer from pain which can not be explained by medical conditions thoroughly . Though Previous research reported about differences in cortical thickness of various brain areas between patients with chronic pain disorders and controls –7. Althoet al. found that patients with major depressive disorder had a smaller hippocampal volume and showed higher plasma levels of IL-6 and C-reactive protein (CRP) than healthy controls . For excontrols . Animal controls  and decrcontrols , 21. Furcontrols  and elevcontrols , 24 in pcontrols , indicatOther evidence suggests an association of early life stress like childhood trauma and pro-inflammatory states in adulthood . Early lSince affective disorders and pain syndromes are often coincident, studies investigated the interaction of both on cortical thickness. While some findings point to vanishing differences in cortical thickness in pain syndromes when controlling for affective disorders , other sIndependent branches of research report about alterations in insular cortical thickness in patients with somatoform pain disorder as well as in people with a history of childhood maltreatment. Moreover, it is well established that patients with somatoform pain disorder often made the experience of childhood maltreatment. To our best knowledge, the interrelationship of these variables has not been addressed yet.We hypothesize that patients diagnosed with somatoform pain disorder express differences in insular cortical thickness compared to healthy controls and that these differences correlate with higher symptom severity. Because studies showed an association between affective disorders and cortical thickness , we use “pain disorder associated with psychological factors” . In this subregion patients showed a mean cortical thickness of 2.27 mm , whereas healthy controls showed a mean cortical thickness of 4.25 mm . Just like the whole brain cortical thickness, the cortical thickness in the identified insular subregion is independent of age for both patients  and healthy controls . In a subsequent analysis we compared the mean cortical thickness of the identified insular subregion between groups while using age, whole brain cortical thickness, and depressive symptoms as nuisance covariates. Group and gender were used as fixed factors. In Though patients tend to a smaller whole brain cortical thickness than the control group, the difference was not significant , somatic symptoms (PHQ-15), and traumatic childhood experiences (CTQ) are presented in The aim of the study was to investigate whether insular cortical thickness differs between patients with somatoform pain disorder and healthy controls. Using voxel-based morphometry we identified a local reduction in cortical thickness in the anterior insular cortex in patients, though the whole brain cortical thickness was the same in both groups. Furthermore, we were interested in associations between insular cortical thickness, symptom severity, and experiences of childhood maltreatment. Whereas significant correlations between insular cortical thickness, symptom severity, and childhood maltreatment were observed in the total collective, associations in the group of patients missed significance.Previous research on insular cortical thickness alterations in pain disorders have shown ambiguous results. Most studies report about a decline in insular cortical thickness and other pain areas in chronic pain syndromes , 7, 10. We found that whole brain cortical thickness, which does not differ between groups, is not associated with age. The same accounts for the identified insular subregion in BA 13. The observation, that insular gray matter volume is age-dependent in patients with fibromyalgia , could nPatients reported significantly more depressive symptoms than healthy controls. Because the influence of affective disorders on brain morphometry is well known, we entered depression in our analysis as a covariate. When Hsu and colleagues controlled for affective disorders, differences in insular gray matter volume between patients with fibromyalgia and healthy controls diminished . We triePatients showed a significantly higher symptom severity than controls. This observation is not surprising given that the control group does not conform to the clinical diagnosis of chronic pain disorder. Nonetheless, occasional experiences of pain were reported by healthy controls as well . The patients/participants provided their written informed consent to participate in this study.YE and YN designed the study. AD and JR provided the MRI data. CF instructed ElM during the preparation and evaluation process of the MR images. EvM supported ElM with the statistical analyses. ElM wrote the first draft of the manuscript. YE, CF and EvM helped in finalizing the manuscript.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.


All participants underwent 36-sessions of training consisting of six exercises. The Vibration group provided vibration stimulation during exercise, but the placebo group did not. The Numeric Pain Rating Scale (NPRS) and digital dual inclinometer were used to measure pain intensity and proprioception. The kinematics of the lumbar spine during STS were measured by motion capture system. After training, the pain and proprioception in the vibration group improved significantly greater than the placebo group (p < 0.05). The mobility of LS  and lumbar-hip coordination during STS in the vibration group were significantly improved compared to the placebo group (p < 0.05). Thus, trunk stabilization exercise combined with vibration may be used to improve the pain, proprioception, and kinematic of the lumbar spine during sit to stand in adolescent patients with LBP.There are many adolescent patients complaining of low back pain, but research on it is lacking. The purpose of this study was to investigate the effects of trunk stabilization exercise combined with vibration on the pain, proprioception, and kinematics of the lumbar spine (LS) during sit to stand (STS) in adolescent patients with nonspecific low back pain (LBP). Fifty LBP patients were recruited and were randomly divided into two groups: Vibration group ( Low back pain (LBP) generally occurs in the early teenage years, and a third of 14 years of age complain of LBP . The preRecently, vibration has been used as a complementary therapy to relieve pain and improve functions in LBP patients ,16,17. VVibration induces muscle contraction by stimulating the stretch reflex, while vibration alternately stimulates momentary muscle relaxation and contraction, activating muscle and nerve fibers and strengthening the neuromuscular system ,24.Most patients with LBP have paravertebral muscle spasms ,25; vibrAs such, vibration stimulation can change the activity pattern of the applied muscle, and this change is expected to affect the improvement and enhancement of LS kinematics. However, until now, most studies that have performed vibration intervention in LBP patients have only suggested the effect on pain and motor dysfunction. Moreover, despite the large number of adolescent patients complaining of LBP, they are not receiving attention in the social or scientific literature .As such, the purpose of this study was to explore the effects of trunk stabilization exercise combined with vibration on pain, proprioception, kinematics of the LS, and lumbar-hip coordination during STS in adolescent patients with LBP.Fifty adolescent patients with nonspecific LBP living in Gimcheon City, Korea participated in this study. The subjects included in the study experienced LBP for 3 months or longer, age between 10 and 19 years, had a visual analogue scale score of 3 or higher, able to perform STS movements without assistance . Exclusin = 25) and the placebo group (n = 25) using a selection envelope. A person who was not involved in the study picked out a number (either 1 or 2) from a sealed envelope for unbiased randomization.The participants were evaluated before and 1–2 days after training for 2 weeks by three well-trained physical therapists, who were not informed on the participants and the purpose of this study. Fifty patients selected by the inclusion criteria were randomly allocated into the vibration group  was used to measure the pain intensity. The score for each item ranges from 0 to 10, measured in units of length up to the location where the patient indicated the level of pain. NPRS is known to have a high sensitivity to pain and is proportional to the pain. This is the most widely used measurement method for chronic pain as well as acute pain with a good reliability .We evaluated and analyzed the repositioning error of the trunk to measure the trunk proprioception. The repositioning error represents the ability of a person to recognize body orientation in space and to adjust and maintain posture, and to measure this, the difference in the angle actively performed by the subject compared to the target angle presented to the subject is measured. This was effectively used as a technique to measure trunk proprioception in previous studies . RepositLumbar kinematics and lumbar-hip coordination during STS were measured and recorded using a motion capture system with 10 infrared cameras , at a sampling rate of 100 Hz. Kinematic data were analyzed using video-motion analysis software named ORTHOTRAK . The markers were placed on T12, S2, greater trochanter, lateral epicondyle, and bilaterally on the anterior superior iliac spine (ASIS) and posterior superior iliac spine (PSIS). The height of the stool was adjusted to 110% of knee-floor length, with the subjects faced forward. When instructed to “start,” subjects were asked to stand up without aid at a comfortable speed, remain standing for 3 seconds, then sit back down. Three consecutive measurements were taken, from which the mean value was used for analysis. Flexion and extension during STS movement were differentiated as two steps in analysis . MaximumSPSS 21.0 was used for statistical analysis. The normality of variables was assessed using the Shapiro–Wilk test. The independent t-test for continuous variables and the chi-square test for categorical variables were used for comparison of the general characteristics of the subjects in the vibration and placebo groups. The paired t-test was used for within-group comparison, and the independent t-test was used for between-group comparison. The level of statistical significance was set at 0.05.p < 0.05)  than in the placebo group  ( < 0.05) .After training, proprioception of the trunk was more significantly increased in the vibration group than in the placebo group. The changeable amount before and after training was −1.32 ± 0.56 and −0.64 ± 0.57°, respectively .−1) compared with the placebo group  (−1) compared with the placebo group   . During 04° s−1) . The mea04° s−1) .The maximum and minimum relative phase difference between hip and LS during STS significantly improved in the vibration group  compared with the placebo group  .This study explored the effect of trunk stabilization exercise combined with vibration on pain in adolescent patients with LBP. Results demonstrated a significant improvement in pain compared to the placebo group. Although there was no clear mechanism by which the pain improved, a few inferences could be made. First, vibration may have decreased pain by suppressing small fibers (A-δ or C fibers) from the pain signal transmitted to the central nervous system and activating large fibers (A-β fibers), closing the pain gate control ,34,35. SSTS and the stand to sit are essential and basic functional movements for the performance of daily life, and not only workers of various occupations, but also LBP patients repeat these movements dozens of times a day for their job and daily life performances ,39. STS Furthermore, when examining the effects of trunk stabilization exercise combined with vibration on the lumbar-hip coordination during STS, significant improvements were observed after the exercises. A study on the lumbar-hip coordination during STS in acute LBP patients reported that the proportion of antagonist and agonist contributions to muscle moments were inversed in LBP patients and that lumbar-hip discoordination occurred following changes in muscle activation patterns. According to the study, the order in which LS flexion took precedent during the initial stage of STS, followed by preceding hip extension during the later stage was identical to that of the control group. However, in the initial stage, LS activation slightly preceded hip activation compared to the control group. In contrast, in the later stage, LS activation had a greater delay than the hip when causing movement . PourahmIn this study, pain and LS kinematics and lumbar-hip coordination during STS were examined following trunk stabilization exercise combined with vibration in LBP patients, and demonstrated significant improvements in all variables. Nonetheless, there were limitations in this study due to the small number of subjects, as well as poor generalizability due to the non-specific nature of LBP patients who were recruited as subjects. In addition, the researchers did not examine sport variables, such as the time or duration of the subject’s participation in sports activities before participating in the study. Since these variables can affect the measurement variables and other physiological factors in this study, further studies are needed to clarify them. Finally, we did not find out the effect of trunk training combined with vibration on the activity pattern of trunk and limb muscles. Therefore, in further studies, it is necessary to prove the effect of exercise training with vibration on the activity pattern of various parts of the body and other physiological variables in order to identify these limitations. In addition, the influence of the subject’s sport variables on exercise intervention will be an interesting topic to be investigated.Our study demonstrated that vibration had significant improvement in pain, proprioception and lumbar kinematics during sit to stand in adolescent patients with nonspecific LBP. The results of this study support previous findings that vibration is effective in improving proprioception and pain in patients with LBP. In addition, the results of this study are the first study to investigate the effect of vibration therapy in adolescent LBP patients and are expected to be used as basic data in adolescent LBP intervention studies including vibration.


Patients and Methods. Data of all patients with chronic OA pain were extracted from the database of a prospective, 3-month noninterventional tapentadol PR trial. The data of elderly OA patients  were compared with the data of younger OA patients .  Tapentadol prolonged release (PR) has been shown effective and generally well tolerated in a broad range of chronic pain conditions. This subgroup analysis investigated its benefits for elderly patients with severe chronic osteoarthritis (OA) pain in routine clinical practice. p ≤ 0.001), and sleep and quality of life measures had also markedly improved in the elderly: quality of sleep by 3 points, quality of life by 3.4 points, social activities by 3 points, and independence by 2.7 points . At the end of observation, 68% of the elderly had clinically relevant pain reductions of at least 50% (vs baseline), and 87.9% attained either their intended pain reduction target and/or an additional individual treatment target (both predefined during baseline examination). Only 8.4% of the elderly experienced adverse drug reactions, most frequently nausea (2.7% of patients) and dizziness (1.5%).  Almost all patients (elderly 98.7% and younger patients 99.3%) had received long-term analgesic medication prior to the start of tapentadol PR treatment but presented with severe pain accompanied by considerable impairments in sleep quality and quality of life measures. Tapentadol PR provided effective pain relief in both patient groups, with slightly better outcomes in younger patients. However, the mean baseline pain intensity of 7.1 (SD 1.5) was reduced by 3.8 points ( Tapentadol PR provided effective and well-tolerated treatment of severe chronic OA pain for elderly patients in routine clinical practice. The favorable tolerability profile in particular suggests tapentadol PR as a treatment option before classical strong opioids are considered. Chronic pain is a common healthcare problem in the general adult population of the European Union and incurs high total population costs . Many chμ-opioid load ) experienced painful OA. Stratification by age resulted in an elderly group (>65 years of age) of 752 patients (72.4%) and a younger group (≤65 years of age) of 282 patients (27.2%); information regarding age was not available for 4 patients. Thus, 1034 patients were included in effectiveness and tolerability analyses. In total, 1038 patients  had already received long-term analgesic treatment prior to the start of tapentadol PR treatment , mainly n = 751/n = 281; multiple responses permitted). Additional reasons were tolerability issues (39.4%/35.6%), insufficient balance between efficacy and tolerability (31.6%/30.3%), lack of compliance (11.9%/15%), and drug interactions with concomitant medication (7.3%/7.5%).Main reasons why patients were switched to tapentadol PR were insufficient analgesia (elderly 90%/younger patients 89.7%) and insufficient quality of life  and 92.3 ± 28.9 days for younger patients (n = 272). The majority of patients in both groups continued tapentadol PR treatment after the treatment follow-up visit at 4–6 weeks (89.2% [667/748]/93.6% [262/280]) and after the 3-month visit (80.5% [603/749]/82.1% [230/280]). Main reasons for treatment discontinuation were unsatisfactory analgesia (8.4%/6.4%), the occurrence of ADRs (6.8%/4.3%), and no further requirement for analgesic treatment . Nineteen elderly (2.5%) and 3 younger patients (1.1%) discontinued treatment due to hospitalization. Reasons included surgery (7 patients), fall (1), stroke (1), coronary heart disease (1), chronic fistula (1), ataxia (1), decompensated diabetes mellitus (1), exsiccosis/refusal to eat (1), and not specified (2). Pain was documented as the reason for hospitalization in four patients ; another elderly patient was hospitalized for periradicular therapy. Only 15 elderly patients (2%) and 2 younger patients (0.7%) discontinued within the first 10 days of tapentadol PR treatment. All cited either the occurrence of ADRs (1.9%/0.7%) and/or unsatisfactory analgesia (0.7%/0.4%) as reason for discontinuation. Initial daily dosing for these patients had been 2 × 50 mg , 2 × 100 mg (5 elderly), and 2 × 150 mg (1 elderly).Mean daily tapentadol PR dosages were comparable between the groups at start of treatment but increased to a greater extent over the observation period in younger patients . Three pn = 750/n = 281). At the end of observation, the proportion of patients with tapentadol PR monotherapy had increased to 32.2% and 36.8%, respectively, and an additional 12.9%/10.7% received tapentadol PR as only long-term medication plus analgesic rescue medication (n = 712/n = 272). Additional long-term analgesics consisted mainly of nonopioids  and 18 patients in the younger age group (6.4%) experienced ADRs during tapentadol PR treatment. The most frequently reported incidences were gastrointestinal and nervous system disorders . “Drug wSerious ADRs were reported for 8 elderly patients  and 2 younger patients . In the elderly group, three patients had one ADR , four patients had two ADRs , and one patient had four moderate ADRs . In the younger age group, drug withdrawal syndrome was documented for one patient and severe fecaloma + severe ileus paralytic for a second patient.At the end of observation, tapentadol PR treatment was rated “good” or “very good” for the majority of patients . PhysiciThe elderly OA patients analyzed here not only presented with painful knee and/or hip OA but also were afflicted by other pain conditions, most notably LBP. Many had been suffering from pain for more than 2 years, and almost all had received long-term analgesic medication before the start of tapentadol PR treatment. Despite this use of, often strong, analgesics (47% of patients were administered WHO III medication), the burden of pain was high: mean pain intensity at baseline was rated as severe and accompanied by considerable impairments in sleep quality and daily functioning, and thus markedly reduced quality of life. Not surprisingly, the main reasons physicians opted for a switch to tapentadol PR were insufficient analgesia and quality of life with previous analgesic treatment.The 3-month treatment with tapentadol PR provided effective pain relief in both patient groups with slightly better outcomes in younger patients. However, a total of 68% of the elderly patients had clinically relevant pain reductions of at least 50% (vs baseline), and 65% achieved their intended pain intensity target. Mean pain intensity at the end of observation deviated by only 0.4 points from the mean treatment target of 3.0 points defined at baseline visit. The results are comparable to findings for the original trial population (72%/66% ) and theNausea, dizziness, and constipation were most frequently reported by the 8.4% of elderly patients experiencing ADRs during tapentadol PR treatment. Only 6.8% discontinued treatment due to the occurrence of an ADR. Physicians considered tapentadol PR treatment well tolerated by the majority of elderly patients, with “good” to “very good” ratings of over 80% in the following categories: gastrointestinal tolerability, CNS tolerability, and general tolerability.Patients suffering from severe pain frequently complain about impairments in daily life such as diminished sleep quality, restrictions in social activities, and loss of independence. These impairments may lead to social isolation, anxiety, and depression, and may thus greatly affect their quality of life. Results for Germany from the 2010 National Health and Wellness Survey showed that the impact of severe and frequent pain on the quality of life is greater than the contribution of sociodemographic factors, the presence of comorbidities, or health risk factors such as obesity, alcohol, and smoking . OA painElderly OA patients received mean daily tapentadol PR doses of 199 ± 101 mg, on average 14 mg less than the younger age group 213 ± 103 mg) at the end of observation and less than half the maximum recommended daily dose of 500 mg. This dosage was at the lower end of the mean daily dose range observed for other routine clinical practice tapentadol PR treatment data in cancer and noncancer pain . ± 103 mgOverall, tapentadol PR was effective and well tolerated in the treatment of painful OA in the elderly in routine clinical practice. The findings complement the positive results of tapentadol PR treatment in elderly patients ≥65 years and ≥75 years of age obtained in pooled analyses of randomized controlled clinical trials , 13.Analyses of routine clinical practice data are limited by the absence of a control group. However, our data which derived from a prospective, noninterventional trial where treatment decisions were solely at the discretion of the treating physician provide an insight into real-world pain management and complement the findings of randomized controlled trials with predefined trial criteria. For example, in contrast to randomized controlled trials with balanced group sizes, the proportion of elderly patients in our analysis was much higher . However, this did not present a problem as no direct statistical comparison between groups was presented and the large number of patients in both groups allowed for a meaningful analysis within both. The lack in balance of potential confounding factors such as gender (higher proportion of women in elderly compared with younger age group) represents a limitation of our analysis, as this makes the groups not directly comparable to each other and might be reflected in the results of the two groups. However, the focus of our analysis was on the effectiveness and safety of tapentadol in elderly patients in a real-life situation in contrast to what is observed in younger patients in real-life rather than a direct comparison of tapentadol PR efficacy between both groups. It should be noted that most patients in this analysis not only suffered from painful OA but also from LBP. Data analysis could not distinguish between the two pathologies. The coexistence of these two pathologies is often observed in clinical practice and is not surprising, given that one could be caused by the other, for example, insufficient pain treatment of OA might lead to issues with posture resulting in subsequent complaints in other body regions such as the lower back.Tapentadol PR provided effective and well-tolerated treatment of severe chronic OA pain for elderly patients in routine clinical practice. The marked improvements in all quality of life measures and the favorable tolerability profile in particular suggest tapentadol PR as an early treatment option before classical strong opioids are considered.


The EQ-5D domain pain/discomfort (PD) uses one item to capture pain and other aspects of discomfort, like itching. This study explored how pain, itching and the EQ-5D-5L PD domain relate to each other in a sample of burn patients.Adult burn patients completed the EQ-5D-5L and the Patient and Observer Scar Assessment Scale (POSAS) 5–7 years after sustaining their injury. The POSAS includes a separate pain and an itching item. Spearman’s correlation coefficient established the association between the EQ-5D-5L PD and the POSAS pain and itching item. With multivariable regression analysis the linear association between the POSAS pain and itching item and EQ-5D-5L PD domain was tested.p < 0.001) and 0.473 (p < 0.001), respectively. Among respondents with pain and without itching and respondents with itching and without pain, Spearman correlation coefficients were 0.585 (p = 0.076) and 0.408 (p = 0.001), respectively. POSAS pain (unstandardized Beta = 0.14) and POSAS itching (unstandardized Beta = 0.08) were significantly associated with EQ-5D-5L PD domain (p < 0.001).Data from 245 patients were included. Mean EQ-5D-5L index value was 0.87 and 39.2% reported at least slight problems on the EQ-5D-5L PD domain. Most patients gave corresponding answers on the EQ-5D-5L PD domain and on the POSAS pain (73%) and itching (70%) item. Spearman correlation coefficients of the EQ-5D-5L PD domain with the POSAS pain and itching were 0.468 .Netherlands Trial Register ( Health-related quality of life (HRQL) assessment is increasingly used to evaluate the consequences of a disease, condition or symptom, to assess the impact of health interventions on these consequences, and to investigate the quality of care –3. An exPain, symptoms and other aspects of discomfort are captured by the EQ-5D domain ‘pain/discomfort’ (EQ-5D PD). However, unlike pain, other symptoms, conditions, or complaints, such as itching, nausea, or feeling breathless, are not explicitly defined. Still, these undefined aspects are assumed to be captured by this domain description. However, one study that explored the extent to which psoriasis symptoms/problems were captured by the PD challenged this assumption [We studied whether itching and pain are (sufficiently) captured by the EQ-5D-5L PD domain, using EQ-5D-5L data as well as separate pain and itching data from burn patients, a specific patient group that experiences pain and/or itching. Chronic pain and chronic itching in various degrees of intensity and frequency are common problems among burn patients –9. Pain Our study aimed to explore how pain, itching and the EQ-5D-5L PD domain relate to each other. First, we investigated how pain and itching, as measured separately through items of the Patient and Observer Scar Assessment Scale (POSAS), relate to the response to the EQ-5D-5L PD. Second, we investigated the association, if any, between the POSAS pain and itching items and the remaining EQ-5D-5L domains. Third, we investigated if variability in pain and itching scores, measured with the POSAS, was captured by the EQ-5D-5L PD domain.The study had a cross-sectional design. Participants included adult burn patients with a hospital stay of ≥1 day or who had surgical treatment in one of the dedicated Dutch burn centres  between August 2011 and September 2012 . This saBetween March 2017 and March 2018, eligible patients were invited to participate via a postal invitation, including an information letter, an informed consent form and the survey. Patients who did not respond within 3 weeks received a phone call  to discuss participation. The study was performed according to the principles of the Declaration of Helsinki, registered at the Netherlands Trial Register (NTR6407), and approved by the Ethics Committee (registration number NL59981).Background information was derived from the Dutch Burn Repository R3 . PatientThe EQ-5D-5L includes items on five domains: mobility, self-care, usual activities, pain/discomfort, and anxiety/depression. Each domain has five ordered response categories: no problems, slight problems, moderate problems, severe problems and extreme problems. An EQ-5D-5L index value was calculated ranging from 0 (death) to 1  based on the answers of the five domains using the Dutch EQ-5D-5L value set , 17. TheItching and pain were separately measured by the POSAS 2.0 (patient part) . The POSR2 ≥ 0.15 . A non-response analysis was performed to study whether responders and non-responders differed. Mann Whitney U tests were used for continuous variables and chi-square tests for categorical variables. Descriptive statistics were used to assess characteristics as well as outcomes of the EQ-5D-5L and the POSAS pain and itching items. Generally, results were studied overall and for the subgroups: patients with versus without comorbidity, and the subgroups patients with pain and no itching (as reported on the POSAS) and patients with itching and no pain (POSAS).IBM SPSS Statistics 23 was used for the analyses. A sample size calculation was performed. A sample size of 118 patients was required when alpha was set at 0.05 and a power of 80%. This enables the detection of Head-to-head comparisons were used to compare outcomes of the EQ-5D-5L PD domain and the POSAS pain and itching items. The proportion of patients with corresponding answers was assessed and tested using a chi-squared test. Corresponding answers were defined as reporting problems on both the EQ-5D-5L PD domain and a POSAS item, so for example for the EQ-5D-5L PD domain and POSAS pain, a patient reported corresponding answers as he/she reported problems on both EQ-5D-5L PD domain (score > 1) and POSAS pain (score > 1). To assess whether the EQ-5D-5L PD domain reflects the worst level of both POSAS items, a POSAS worst count variable was created based on the POSAS pain and itching items. So, if POSAS pain was scored higher (worse) than POSAS itching, this score was used in the worst level variable, or vice versa. The worst outcome was compared with the EQ-5D-5L PD domain outcome.r ≥ 0.50, moderate if r ≥ 0.30–0.49, and weak if r ≥ 0.10–0.29 [We used the Spearman rank correlation coefficient to establish convergent validity of the EQ-5D-5L PD using the POSAS items as reference. Rank order correlation between the EQ-5D-5L PD domain and POSAS pain and itching items, as well as between all other EQ-5D-5L domains and POSAS pain and itching items were studied, both in the total sample as in the defined subgroups . Both th.10–0.29 .p < 0.05.Then, it was assessed to what extent variability in pain and itching was captured by the EQ-5D-5L PD domain. The correlation between the POSAS pain and itching item and the correlation with the EQ-5D-5L PD domain was studied. For each combination of POSAS pain and itching outcomes, the mean EQ-5D-5L PD domain score was calculated. Multivariable regression analyses were applied to predict EQ-5D-5L PD domain from the POSAS pain and itching items, with relevant demographic  and clinical variables  added. Lastly, the EQ-VAS was predicted by the POSAS pain and itching items, as well as by the EQ-5D-5L PD. The significance level for all analyses was set at Itching is captured by the EQ-5D-5L PD, which is tested by the presence of problems on the EQ-5D-5L PD domain for the subgroup of patients who do not score problems on POSAS pain, but do score problems on POSAS itching.The association between the EQ-5D-5L PD domain scores and the POSAS pain item score is of comparable magnitude compared to the association between the EQ-5D-5L PD domain and the POSAS itching item score. If both symptoms coincide, the EQ-5D-5L PD domain reflects the worst level of both POSAS items.The EQ-5D-5L PD domain score is stronger related to the POSAS pain item score in patients without rather than with comorbidity, because patients with comorbidity have a higher probability to experience pain due to their comorbid chronic disease.The association between the other EQ-5D-5L domains and the POSAS pain and itching items is lower compared to that between EQ-5D-5L PD domain and the same items.There is a strong correlation between the EQ-5D-5L PD domain score and the POSAS pain and itching item score.p = 0.03) and were older (p < 0.01) than non-responders  completed all items of the EQ-5D-5L and POSAS and were included in this study. Non-response analysis showed that responders were more often females  and the mean EQ-VAS was 81.6 (SD 15.7) (Table 8 and then = 67) reported non-corresponding answers on the POSAS pain item and EQ-5D-5L PD domain (Table n = 50) reported no pain on the POSAS and slight to severe problems on the EQ-5D-5L PD domain. Chi square test showed that answers on both items were related (X2 (1)=40.735; p < 0.001). For patients with comorbidity, the percentage of respondents with non-corresponding answers was 34%, of which most (81%) reported no pain on the POSAS and slight to severe problems on the EQ-5D-5L PD domain. For patients without comorbidity, the percentage of respondents with non-corresponding answers was 25%, with 72% of them reporting no pain on the POSAS and slight to severe problems on the EQ-5D-5L PD domain. Of the 10 respondents who reported pain and no itching (POSAS), 70% reported problems on the EQ-5D-5L PD domain. For respondents with and without comorbidity, this percentage was 67 and 81%, respectively.In total, 27% of the patients (n = 74) (Table n = 48) reported itching on the POSAS and no problems on the EQ-5D-5L PD domain. Chi square test showed that answers on both items were related (X2 (1)=38.741; p < 0.001). For patients with comorbidity, the percentage of respondents with non-corresponding answers was 31%, of which 33% reported itch on the POSAS and no on the EQ-5D-5L PD domain. For patients without comorbidity, 29% gave non-corresponding answers, with 75% of them reporting itch on the POSAS and no problems on the EQ-5D-5L PD domain. Of the 65 respondents who reported itching and no pain (POSAS), 48% reported problems on the EQ-5D-5L PD domain. For respondents with and without comorbidity, this percentage was 70 and 44%, respectively.Non-corresponding answers on the POSAS itching item and EQ-5D-5L PD domain were given by 30% of the patients (4) Table , of whicA total of 70 patients (29%) gave non-corresponding answers on the POSAS worst count variable versus the EQ-5D-5L PD domain. Most of them (73%) reported pain and/or itching on the POSAS and no pain/discomfort on the EQ-5D-5L PD domain. Comparing patients reporting no problems, 117 patients (48%) reported no problems on the combined POSAS variable, whereas 149 patients (61%) reported no problems on the EQ-5D-5L PD domain.p < 0.001) and 0.473 (p < 0.001), respectively. In the subgroup of patients reporting pain but no itching on the POSAS, Spearman’s rank correlation coefficient was 0.585 (p = 0.076), indicating a strong correlation. In the subgroup of patients with itching and no pain, the correlation was 0.408 (p = 0.001), indicating a moderate correlation. The correlation between the EQ-5D-5L PD domain and the POSAS pain item and between the EQ-5D-5L PD domain and the POSAS itching item were comparable in respondents with and without comorbidity.Spearman rank correlation coefficients of the EQ-5D-5L domains and the POSAS pain and itching items are displayed in Table p < 0.001).In the total sample, the rank correlation between the EQ-5D-5L PD domain and the combined worst count POSAS variable was 0.530 (p = 0.121) for self-care to 0.359 (p < 0.001) for usual activities (Table p = 0.368) for mobility to 0.301 (p < 0.001) for usual activities.The correlation coefficients of the other EQ-5D-5L domains and the POSAS pain item ranged from 0.099 (p < 0.001), indicating a moderate correlation between both POSAS items.Outcomes of the EQ-5D-5L PD domain versus POSAS pain outcomes are displayed in Fig. p < 0.001).Multivariate regression analysis showed that POSAS pain (unstandardized Beta = 0.14) and POSAS itching (unstandardized Beta = 0.08) were significantly associated with the EQ-5D-5L PD domain (both p = 0.040), but not POSAS itching  was significantly associated with the EQ-5D-5L PD domain. In respondents without comorbidity, however, both POSAS items pain  and itching  were significantly associated with the EQ-5D-5L PD domain.In respondents with comorbidity, POSAS pain  with the EQ-VAS, whereas the EQ-5D-5L PD domain was found to be associated   and POSAS itching (unstandardized Beta = − 0.16) were not significantly associated  compared to the composite dimension (43% of sample reporting problems), however, this difference was not statistically significant . InteresOur results confirm our first hypothesis that the correlation between the EQ-5D-5L PD domain and the POSAS pain item is comparable to the correlation between the EQ-5D-5L PD domain and the POSAS itching item. Only a small percentage of patients reported non-corresponding answers, e.g. no problems on the EQ-5D-5L PD domain (score = 1), and problems on the POSAS pain (score > 1). Part of this inconsistency may be the consequence of differential instruction: the POSAS was completed for the patients –in their opinion– worst scar. The EQ-5D-5L PD domain on the other hand, reflects the patient’s overall condition. Most patients (75%) that reported inconsistently outcomes, reported pain in the EQ-5D-5L PD domain and yet no pain on the POSAS pain item. A possible explanation for this finding may be that pain outside the scar may have a relation to a pre-existing condition (comorbidity). However, the correlation between the EQ-5D-5L PD domain and the POSAS pain item was higher rather than lower in the group patients without comorbidity than in the group with comorbidity. For itching, a different pattern was observed; most patients with inconsistent answers reported itching on the POSAS itching item, but no PD in the EQ-5D PD domain. Potentially because these patients did not consider itching as discomfort, because of fluctuations of itching levels, or because they simply overlook the discomfort addition.Subgroup analysis, in patients with respectively pain and itching, showed that EQ-5D-5L PD domain and POSAS pain had a good correlation, whereas the EQ-5D-5L PD domain and POSAS itching showed a moderate correlation. Pain seems thus to be sufficiently covered by the EQ-5D-5L PD; however, results on itching are less conclusive in our sample of burn patients. An earlier study in psoriasis patients identified ‘skin irritation, including itching’ as a separate candidate domain. Psychometric analyses showed that the new domain captured additional variance over the existing five EQ-5D-5L domains [This study has strengths and limitations. A strength was the unselected cohort nature, and the high prevalence of pain and itching which allowed us to study whether itching and pain are captured by the EQ-5D-5L PD domain, including interaction effects. Another strength was that both instruments were validated in the burn population , 24. A lOur findings indicate that, in a sample of burn patients, pain and itching are captured by the broader EQ-5D-5L PD domain. The EQ-5D-5L PD domain can thus be used to assess pain and itching in relation to HRQL, but the POSAS pain and itching items are more sensitive. The EQ-5D-5L is, however, no replacement of the POSAS when the POSAS is used for its primary aim; assessment of scar quality.Additional file 1. Characteristics of adult responders versus non-responders.Additional file 2. Multivariate model for the EQ-VAS, including EQ-5D-5L pain/discomfort domain, POSAS pain and itching item, and relevant demographic and clinical factors.


Fibromyalgia is the most common of the central sensitivity syndromes affecting 2–5% of the adult population in the United States. This pain amplification syndrome has enormous societal impact as measured by work absenteeism, decreased work productivity, disability and injury compensation and over-utilization of healthcare resources. Multiple studies have shown that early diagnosis of this condition can improve patient outlook and redirect valuable healthcare resources towards more appropriate targeted therapy. Efforts have been made towards improving diagnostic accuracy through updated criteria. The search for biomarkers for diagnosis and verification of Fibromyalgia is an ongoing process. Inadequacies with current diagnostic criteria for this condition have fueled these efforts for identification of a reproducible marker that can verify this disease in a highly sensitive, specific and reproducible manner. This review focuses on areas of research for biomarkers in fibromyalgia and suggests that future efforts might benefit from approaches that utilize arrays of biomarkers to identify this disorder that presents with a diverse clinical phenotype. The National Institutes of Health (NIH) defines biomarkers as: “characteristics that can be objectively measured and evaluated as an indication of normal or pathogenic processes or pharmacological responses to a therapeutic intervention“ . StudiesSome of the most common and difficult to treat disorders in medicine are the “medically unexplained symptoms” ,4 or “ceFibromyalgia is a clinical syndrome characterized by a dysregulation of neuroendocrine function and/or nociceptive processing. The clinical manifestations of FM include global widespread pain often accompanied by an associated sleep disturbance ,5,6. TheMusculoskeletal complaints account for over 20 million ambulatory care visits annually ,9. RetroTherapy for FM is hampered by lack of consistent, evidence-based management guidelines. Pain processing requires transmission from peripheral tissues to the brain and can be modulated by both endogenous and exogenous processes. Physical, psychological, and pharmacologic interventions can help to modulate the perception of pain in affected individuals. The initial focus and the base of any treatment protocol involves physical therapy aimed at improved conditioning. Selective serotonin reuptake inhibitors (SSRI), serotonin norepinephrine reuptake inhibitors (SNRI), alpha 2 delta ligands, and tricyclic antidepressants form the therapeutic armamentarium as we seek to modulate the neurochemical pain pathways present in the brain. Unfortunately, treatment often fails to lead to adequate recovery, frustrating both the patient and physician ,5,6,7.The initial 1990 American College of Rheumatology (ACR) diagnosis of FM was heavily weighted on the presence of painful tender points in a global distribution ,21. NotwAlthough many criteria have been put forth and multiple revisions have ensued over the last three decades, problems still are present with acceptance of criteria, delayed diagnoses, use of criteria in general practice, and as a result, misdiagnosis of patients remains rampant. A push to move initial identification, diagnosis, and treatment of FM to generalists rather than specialists has not enhanced diagnostics, treatment, or quality of life ,26,27,28Discovery of a reliable biomarker for FM would be a critical step towards early intervention in this condition, as well as help to contain health care and/or legal costs. Annemans and colleagues  have shoFunctional magnetic resonance imaging (FMRI) has been utilized to document aberrant sensitization in the central nervous system (CNS) of individuals with FM . In an iThe stress response may elicit variable changes in heart rate, which might in turn serve as a biomarker. For example, it is possible to identify individuals within the same general group of subjects who display marked differences in magnitude and duration of their neuroendocrine responses to various stressors . Heart r158met has been shown to play a role in variation to temporal summation to pain, whereas other SNPs exert influence on resting nociceptive sensitivity. Interestingly, certain haplotypes of the TRPV2 gene have been implicated as playing a protective role against the clinical symptoms of FM. In summary, a number of genetic markers and polymorphisms have been identified as showing associations in subsets of FM patients; however, none have clearly been able to show consistent variation with disease activity, nor have any been shown to display widespread clinical utility [Evidence of familial associations has been documented in FM with corroboration that first-degree relatives of individuals with FM patients are more likely to suffer from comorbid conditions like chronic fatigue syndrome, irritable bowel syndrome, temporomandibular joint dysfunction (TMJ), migraines, and other regional pain syndromes ,33,34,35 utility ,38,39,40Much work is also being done on the genetic front using technology gleaned from genome-wide association studies . GCH1 gep = 0.03) and MCP-1 increased by 9.4 pg/mL (p = 0.006). Body mass index (BMI), medications, severity of depression, and overall FM burden were not found to significantly be associated with either IL-8 or MCP-1. They theorized that there are increased amounts of skin mast cells in FM [Another set of putative biomarkers includes IL-8 and MCP-1 . Ang andls in FM ,45 alongls in FM ,47,48,49Obesity has been explored as a possible biomarker . Okifuji2 = 0.30). There was no specific abnormality of FM associated with very high levels of tender points other than the level of distress. The suggestion was that tender points might function as a form of “erythrocyte sedimentation rate” for patients with FM. As a result, the diagnostic significance of tender points was thrown into question, and they were no longer included as essential in more recent versions of diagnostic criteria, but even that move has been subject to debate [Global widespread pain has been one of the prime characteristics of identifying individuals with FM. Earlier versions of diagnostic criteria included “tender point counts” as crucial in identifying if individuals had FM or not. Earlier randomized prospective studies showed improvement in clinical pain correlating with decreases in tender point count; however, other studies have failed to show these same findings . In a lao debate .Alternative evoked pain measures (other than tender point counts and dolorimetry) have been sought for a number of years. This is because these latter two approaches can both be modulated by levels of distress and/or expectancy. Pressure pain thresholds, and heat and cold pain thresholds, have been utilized in research settings and are not yet automated to the point of being useful as clinical/bedside parameters for clinical assessment ,55,56,57Sleep architecture has been shown to be disrupted with the presence of alpha wave intrusion on polysomnography graphs since the classic experiments of Moldofsky . The orin = 13), FM and chronic fatigue syndrome (CFS) (n = 12), or CFS (n = 15) who were matched by age (18–65), sex, and menstrual status to healthy controls. Blood collection was done every 10 min over 24 h for analysis of adrenocorticotropic hormone (ACTH) and cortisol. Samples were evaluable for ACTH in 36 subject pairs and for cortisol in 37 subject pairs. There was a significant delay in the rate of decline from acrophase to nadir for cortisol levels in patients with FM (p < 0.01). However, inconsistent results have been obtained in multiple studies of basal plasma cortisol, salivary basal and diurnal cortisol, and urinary cortisol, making these measures generally unreliable. Therefore, these measurements cannot be used on a widespread basis.The most consistent finding regarding the hypothalamic-pituitary–adrenal axis system in FM subjects has been a flattening of the diurnal plasma cortisol level with an elevated trough . CrofforThe presence of anti-serotonin antibodies was reported by Klein and colleagues in 1992 . In ordep < 0.001). This finding replicated prior studies of Vaeroy [p < 0.0001). Of note, plasma samples of NGF and BDNF have not displayed the elevations in FM subjects relative to non-pain controls seen in CSF or serum in multiple studies [p < 0.001; r = 0.53, p < 0.01) and glutamate  relative to the control group. Findings suggested that lower brain serotonin levels might be associated with decreased transport ratios of plasma tryptophan [Tryptophan metabolism has been implicated in FM pathology due to possible roles of its metabolites in sleep, fatigue, and pain propagation. Changes in melatonin (MT) secretion and/or availability may have consequences on sleep preservation. Two MT precursors (tryptophan and serotonin) which affect both sleep and pain perception appear to be low in patients with FM. Previous studies have tried to determine whether serum MT (s-MT) level was also low in these patients. Eight patients with FM and 8 controls were included in the study. FM patients had a 31% lower MT secretion than controls during the hours of darkness. Also, the s-MT peak value was significantly lower in FM . Plasma yptophan .Various muscle abnormalities have been reported in FM . These aOne of the more recently identified abnormalities that has been consistent is indicative of a small-fiber neuropathy (SFN) . SeveralWallace and colleagues have reported on the development of a chemokine and cytokine multiplex immunoassay after mitogenic stimulation with the goal of improving and achieving an accurate diagnosis of FM. Their study involved the use of isolated mononuclear cell. These monocytes were stimulated and supernatants were assayed for measurement of the following cytokines and chemokines of interest; IL-6, IL-8, MIP-1 alpha and MIP-1 beta. The analyses included 160 patients with FM, 98 with RA, and 100 with SLE who were subsequently compared to 119 controls. Sensitivity, specificity, positive predictive, and negative predictive value for having FM compared to controls (SLE and RA) were 93, 89, 92, and 91%, respectively. The authors concluded that evaluating cytokine and chemokine profiles in stimulated cells revealed patterns that are uniquely present in patients with FM. They felt that this assay could be a useful tool in differentiating systemic inflammatory autoimmune processes from FM and healthy controls .n = 50), RA (n = 29), OA (n = 19), or SLE (n = 23) were analyzed [p < 0.05, and interclass distances > 2.5). Spectra correlated  with FM pain severity measured with fibromyalgia impact questionnaire (FIQR) assessments. Protein backbones and pyridine-carboxylic acids appeared to drive the discrimination ability. Further analysis of unique metabolites driving discrimination was achieved by uHPLC-PDA-MS/MS. These studies may lead to specific therapeutic targets for establishing serologic biomarkers of FM-associated pain. The approach of the Hackshaw group has been independently corroborated by Passos, who has also utilized vibrational spectroscopy. Passos and colleagues evaluated 126 controls and 126 patients with FM using Fourier Transform Infrared (FTIR) spectroscopy in conjunction with chemometric techniques. A genetic algorithm with linear discriminant analysis was found which achieved their best diagnostic results with a sensitivity of 89.5% in an external test set. Amide II (1545 cm) and proteins 1425 cm were identified to be discriminant features. Their results reinforce the prior results of Hackshaw in showing the potential of vibrational spectroscopy with multivariate analysis as a tool to screen and detect patients with FM in a rapid, low-cost, and minimally invasive manner [Hackshaw and colleagues identified a biomarker “fingerprint” for FM in serum using an infrared microspectroscopy-chemometric (IRMS-C) approach . IRMS-C analyzed . Portable manner .Vibrational (mid-IR and Raman) spectroscopy is a way of providing a non-destructive biochemical fingerprint or signature on a wide range of biologic samples. In contrast, NMR spectroscopy and mass spectrometry (MS) techniques, although providing potential for specificity of the biologic sample of interest, require costly instrumentation, are labor-intensive, and involve complex sample preparation. Thus, this type of methodology is not point-of-care ready. Advances in the last few years through micro-electro-mechanical systems (MEMS) technological developments has led to miniaturization of vibrational spectrometers and the potential for bedside clinical analyses in the future through the use of portable units . Interesp < 0.001). OA moderate and severe pain patients showed significantly lower Mu+ B cell percentages than mild pain OA and negative control patients (p < 0.01). Possibilities posed by these studies include the use of immunophenotyping as a biomarker for chronic pain and ease of this type of peripheral analysis.Recently, the mu opioid receptor on B lymphocytes has been evaluated as a potential biomarker for FM and osteoarthritis (OA) patients . Blood sIn summary, there are many promising research fronts that are being pursued for identification of a biomarker in FM. As these investigations proceed, we continue to learn more about the pathogenesis of this condition. Most probably, FM is a clinical phenotypic end point approached through diverse pathogenetic mechanisms. As a result, it is probable that multiple biomarkers may need to be utilized depending upon the clinical presentation. Whether the diversity of the inciting mechanisms might be reflected in subsequently identified biomarker(s) awaits future discovery. If found, they would help provide clues towards the most appropriate treatment avenues.Our current approach towards treatment of FM involves physical, psychological, and pharmacologic interventions, all aimed at modulating the perception of pain and pain propagation in affected individuals. Physical therapy is the initial focus characterized by a self-directed or interventional teaching program followed by a self-directed exercise approach. The aim of such programs is to improve conditioning. Later therapeutic options include attempts to modulate the neurochemical pain pathways present in the brain. Tricyclic antidepressants, selective serotonin reuptake inhibitors (SSRI), serotonin norepinephrine reuptake inhibitors (SNRI), and alpha 2 delta ligands are the mainstays of the therapeutics used for these purposes. Treatment is often inadequate, resulting in incomplete recovery or pain improvement levels of only 30% over baseline, which limits the potential efficacy of these therapeutics . The lis


To compare the effects of Cranio cervical flexion training with and without pressure biofeedback on deep cervical muscular endurance in patients with mechanical chronic neck pain.A randomized control trial was conducted at Railway General Hospital Rawalpindi, from May to December 2019. It consisted of thirty participants with the age ranging from 25 to 40 years, and having chronic mechanical neck pain. The participants were randomly allocated into two groups Group-A received Craniocervical flexion training with pressure biofeedback and Group-B received Craniocervical flexion training without pressure biofeedback. The intervention was applied for four weeks (3 sessions per week). Assessments were taken at Pre, Post intervention and after six weeks of follow up. Data analysis was done using SPSS-21 version.The mean age of Group-A and Group-B was 29.40±3.08 and 31.33±4.95 respectively. Between-group analyses has shown statistically and clinically significant improvement in Group-A regarding deep neck muscles endurance (p<0.05). Whereas within group analysis of both groups A & B showed a statistical and clinically significant difference (p=0.00) for deep neck muscles endurance.Cranio-cervical flexion training with Pressure Biofeedback has proven to be more effective in improving endurance of deep cervical flexors in patients with mechanical neck pain. Neck pain affects approximately 70% of people at some point in their lifetime.7Maintenance of proper posture is found to be an important factor in management of neck pain.11Previous studies have been revolving around therapeutic measures of superficial cervical muscles in patients with mechanical neck pain whereas scant amount of studies have been conducted on deep neck flexors training for alleviation of neck pain and endurance.This randomized control trail was conducted in physiotherapy department of Railway General Hospital Rawalpindi after obtaining ethical approval from research ethical committee of Riphah College of Rehabilitation & Allied Health Sciences. (Ref. No. Riphah/RCRS/REC/00559) from May 2019 to December 2019. The present study trial was registered at www.ClinicalTrails.gov with registry number NCT04173143. Participants selected through non-probability purposive sampling technique. Sample size was calculated by Openepi version 3 software, using NPRS variable values, level of significance was kept 0.5 and power of the study was 0.80. The calculated sample size was 24 but it was extrapolated to 30 to handle drop outs.Craniocervical Flexion Test (CCFT). Inter rater reliability (ICC) of DNF Endurance Test (hold time in sec) is 0.82-.91.CCFT(mmHg) range from 0.81 to 0.98.19The primary outcome measure of the study was endurance of DCF which was measured by Deep Neck Flexor (DNF) Endurance Test and After initial assessment all the subjects were randomized into two groups. Group-A received Craniocervical flexion training with pressure biofeedback, Patients were asked to lie in supine hook lying position. Pressure biofeedback unit’s inflated to 20mmHg and was positioned behind the neck and the dial which was connected to the pressure sensor, was given to the patient. Patients were advised to perform Craniocervical flexion action to progressively target  and hold the 5 pressure levels for 10 second between 22 mm Hg and 30 mmHg. A 2-minute second rest period was provided between each level. Session was performed thrice in a week. Each session was given for approximately 20 minutes.16The data was analyzed using SPSS Version 21. Shapiro Wilk test was applied to check normality of data. Parametric tests were applied on the data for p-value > 0.05 and non-Parametric test were applied on the data for p-value < 0.05.The total 30 number of participants were analyzed , the mean age of Group-A was 29.40±3.08 years, whereas for Group-B it was 31.33±4.95 years. The mean BMI of Group-A was 22.18±4.01, whereas for Group-B it was 23.47±2.23. Among total individuals, 20(%) were females and 10(%) were males in both Groups.At pre-test level NPRS and endurance scores both in (mmHg) and (hold time in sec) were recorded. Second assessment was done for the said outcome measures after four weeks of intervention by the physical therapist. Patients followed home exercise interventions for further two weeks and then final measurements were taken after 6 weeks follow up (FU)th week (p<0.05) as well as at Follow up (p<0.05).Group analyses, in which comparison was done using independent T Test. is shown in th week (p<0.05) as well as at Follow up (p<0.05).Results of within Group-A analysis are shown in Neck pain is commonly prevalent chronic disorder with increasing economic burden to the society. A functional contributing factor to chronic mechanical neck pain may be the altered motor function of the cervical spine and its related micro and macro damage.The present study findings indicated that pressure biofeedback training is more efficient to improve neck pain. A similar study has been conducted by M Karthi et al. 2019) on efficacy of endurance training on deep cervical flexor muscles using pressure feedback in mechanical neck pain. They have concluded that Deep Cervical Flexor Training with Visual Pressure Biofeedback was significantly effective (p<0.005) for reduction in neck pain than the conventional training. on efficIt is evident from literature that poor endurance of neck muscles is considered a risk factor for mechanical neck pain. So, interventions targeted for its improvement given more emphasis in neck pain management protocols. The results of the present study have showed that individuals receiving Cranio cervical flexion training with pressure biofeedback unit improved more in deep neck flexor endurance measured (both in mmHg and hold in sec). These results are supported by M Karthi et al on efficacy of endurance training on deep cervical flexor muscles using pressure feedback in mechanical neck pain. Between-group and within the group analysis showed a statistical and clinically significant difference in terms of endurance.24Due to practice pattern and gender based ethical concerns of clinical site, less male patients were recruited & male to female ratio was therefore 1:3. Further, It was researcher’s concern that the postures of study participants observed in a photographic analysis might not be true reflection of the one adopted while working. This study has provided a useful insight and addition in treatment protocol of mechanical neck pain using a valid intervention technique. The study should be done with larger sample size and by recruiting equal number of male patients. To improve the internal validity of the study, assessor blinding should be followed. Long term effects of interventions are needed to be followed.Cranio-cervical flexion training with pressure biofeedback proves to be more clinically effective in terms of neck pain and endurance. So, this specific, easy to use intervention is recommended to be part of routine physical therapy protocol for patients with chronic mechanical neck pain.HR & RA: conceived, designed and did statistical analysis & editing of manuscriptRA & HR: did data collection and manuscript writingRA & HR: did data analysis and interpretation, accountable for integrity of work.HR: did critical review, rechecked information accuracy and final approval of manuscript.