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Wnt signaling pathway inhibitors, sclerostin and DKK-1, correlate with pain and bone pathology in patients with Gaucher disease.

Patients with Gaucher disease (GD) have progressive bone involvement that clinically presents with debilitating bone pain, structural bone changes, bone marrow infiltration (BMI), Erlenmeyer (EM) flask deformity, and osteoporosis. Pain is referred by the majority of GD patients and continues to persist despite the type of therapy. The pain in GD is described as chronic deep penetrating pain; however, sometimes, patients experience severe acute pain. The source of bone pain is mainly debated as nociceptive pain secondary to bone pathology or neuropathic or inflammatory origins. Osteocytes constitute a significant source of secreted molecules that coordinate bone remodeling. Osteocyte markers, sclerostin (SOST) and Dickkopf-1 (DKK-1), inactivate the canonical Wnt signaling pathway and lead to the inhibition of bone formation. Thus, circulated sclerostin and DKK-1 are potential biomarkers of skeletal abnormalities. This study aimed to assess the circulating levels of sclerostin and DKK-1 in patients with GD and their correlation with clinical bone pathology parameters: pain, bone mineral density (BMD), and EM deformity. Thirty-nine patients with GD were classified into cohorts based on the presence and severity of bone manifestations. The serum levels of sclerostin and DKK-1 were quantified by enzyme-linked immunosorbent assays. The highest level of sclerostin was measured in GD patients with pain, BMI, and EM deformity. The multiparameter analysis demonstrated that 95% of GD patients with pain, BMI, and EM deformity had increased levels of sclerostin. The majority of patients with elevated sclerostin also have osteopenia or osteoporosis. Moreover, circulating sclerostin level increase with age, and GD patients have elevated sclerostin levels when compared with healthy control from the same age group. Pearson's linear correlation analysis showed a positive correlation between serum DKK-1 and sclerostin in healthy controls and GD patients with normal bone mineral density. However, the balance between sclerostin and DKK-1 waned in GD patients with osteopenia or osteoporosis. In conclusion, the osteocyte marker, sclerostin, when elevated, is associated with bone pain, BMI, and EM flask deformity in GD patients. The altered sclerostin/DKK-1 ratio correlates with the reduction of bone mineral density. These data confirm that the Wnt signaling pathway plays a role in GD-associated bone disease. Sclerostin and bone pain could be used as biomarkers to assess patients with a high risk of BMI and EM flask deformities.

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Effects of active musical engagement during physical exercise on anxiety, pain and motivation in patients with chronic pain.

The experience of anxiety is central to the development of chronic pain. Music listening has been previously shown to exert analgesic effects. Here we tested if an active engagement in music making is more beneficial than music listening in terms of anxiety and pain levels during physical activity that is often avoided in patients with chronic pain. We applied a music feedback paradigm that combines music making and sports exercise, and which has been previously shown to enhance mood. We explored this method as an intervention to potentially reduce anxiety in a group of patients with chronic pain (= 24, 20 female and 4 men; age range 34-64, 51.67,  = 6.84) and with various anxiety levels. All participants performed two conditions: one condition, , where exercise equipment was modified with music feedback so that it could be played like musical instruments by groups of three. Second, a where groups of three performed exercise on the same devices but where they listened to the same type of music passively. Participants' levels of anxiety, mood, pain and self-efficacy were assessed with standardized psychological questionnaires before the experiment and after each condition. Results demonstrate that exercise with musical feedback reduced anxiety values in patients with chronic pain significantly as compared to conventional workout with passive music listening. There were no significant overall changes in pain, but patients with greater anxiety levels compared to those with moderate anxiety levels were observed to potentially benefit more from the music feedback intervention in terms of alleviation of pain. Furthermore, it was observed that patients during more strongly perceived motivation through others. The observed diminishing effects of on anxiety have a high clinical relevance, and in a longer term the therapeutic application could help to break the Anxiety Loop of Pain, reducing chronic pain. The intervention method, however, also has immediate benefits to chronic pain rehabilitation, increasing the motivation to work out, and facilitating social bonding.

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Optimal modes of mind-body exercise for treating chronic non-specific low back pain: Systematic review and network meta-analysis.

There were limited studies that directly compare the outcomes of various mind-body exercise (MBE) therapies on chronic non-specific low back pain (CNLBP).

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Editorial: Whiplash-associated disorder-advances in pathophysiology, patient assessment and clinical management.

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Dorsal root ganglion pulsed radiofrequency using bipolar technology in patients with lumbosacral radicular pain duration ≥ 2 years.

Transforaminal epidural steroid injection (TFESI) or dorsal root ganglion pulsed radiofrequency (PRF) are alternative treatments for lumbosacral radicular pain (LSRP). This study aimed to investigate the clinical efficacy of TFESI combined with dorsal root ganglion PRF using bipolar technology to treat LSRP in patients with pain duration ≥ 2 years.

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Potential value of serum brain-derived neurotrophic factor, vascular endothelial growth factor, and S100B for identifying major depressive disorder in knee osteoarthritis patients.

The chronic pain and functional limitations in osteoarthritis (OA) patients can increase risk of psychiatric disorders, e.g., major depression disorder (MDD), which may further aggravate the clinical symptoms of OA. Early detection of MDD is essential in the clinical practice of OA.

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Relations between short-term memory and the within-subject variability of experimental pain intensity reports: Results from healthy and Fibromyalgia patients.

While factors contributing to between-subjects differences in pain have been studied extensively, factors contributing to the within-subjects variability of pain reports are yet unexplored. The aim of this investigation was to assess possible associations between short-term memory and the within-subjects variability of pain reports in healthy and chronic pain patients. Healthy participants were recruited at the University of Haifa, Israel, and Fibromyalgia patients were recruited at a rheumatology department in a central hospital in Lisbon, Portugal. Following consent, both cohorts underwent the same procedures, including the digit-span test, assessing short-term memory, and the FAST procedure, assessing within-subject variability of pain intensity reports in response to experimental pain. One-hundred twenty-one healthy volunteers and 29 Fibromyalgia patients completed the study. While a significant correlation was found between the within-subjects variability and the total score of the short-term memory task (Spearman's r = 0.394, P = 0.046) in the Fibromyalgia group, a marginal correlation emerged in the healthy cohort (r = 0.174, P = 0.056). A possible interpretation of these results is that in the patients' group, at least some of the within-subjects variability of pain intensity reports might be due to error measurement derived by poorer short-term memory, rather than true fluctuations in perception.

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Attaining expert consensus on diagnostic expectations of primary chronic pain diagnoses for patients referred to interdisciplinary pediatric chronic pain programs: A delphi study with pediatric chronic pain physicians and advanced practice nurses.

Pediatric primary chronic pain disorders come with diagnostic uncertainty, which may obscure diagnostic expectations for referring providers and the decision to accept or re-direct patients into interdisciplinary pediatric chronic pain programs based on diagnostic completeness. We aimed to attain expert consensus on diagnostic expectations for patients who are referred to interdisciplinary pediatric chronic pain programs with six common primary chronic pain diagnoses.

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The contribution of the left precuneus to emotion memory in migraine without aura patients.

The impact of migraine without aura (MWoA) on cognitive function remains controversial, especially given the sparse literature on emotional memory.

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Defining pain-validation: The importance of validation in reducing the stresses of chronic pain.

To validate an individual's feelings or behaviour is to sanction their thoughts or actions as worthy of social acceptance and support. In contrast, rejection of the individual's communicated experience indicates a denial of social acceptance, representing a potential survival threat. Pain-invalidation, though ill-defined, appears to be a fundamental component of psychosocial stress for people with chronic pain. As such, the aim of this paper was to define pain-validation and outline its importance for those with chronic pain.

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