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No long-term effects after a three-week open-label placebo treatment for chronic low back pain: a three-year follow-up of a randomized controlled trial.

Chronic low back pain is prevalent, highly disabling and a relevant socioeconomic health concern. Although allocated to placebo groups, patients in randomized controlled trials show significant pain relief, pointing to the relevance of placebo effects. Overcoming ethical and legal concerns related to deceptive placebos, recent studies have demonstrated the efficacy of short-term treatments for chronic low back pain with open-label (i.e., non-deceptive) placebos. However, data on long-term efficacy of open-label placebos are sparse. Here, we report a three-year follow-up of our previously published randomized controlled trial demonstrating pain reduction, improvement in disability and depressive symptoms after a three-week treatment with open-label placebos. Including records from N=89 previously enrolled patients, we investigated changes between the groups with and without previous open-label placebo treatment in pain intensity (primary outcome), disability and mood (secondary outcomes), biopsychosocial factors and lifestyle (exploratory outcomes) from parent baseline to follow-up. Over the three-year period, there were no differences in any outcome between groups with and without open-label placebo treatment. Therefore, our follow-up data do not support the previously suggested assumption that a three-week open-label placebo treatment has long-term effects. This study was pre-registered on April 14, 2020, in the German Clinical Trials Register (registration number DRKS00021405).

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Experiences of medical traumatic stress in parents of children with medical complexity.

Parents of children with medical complexity (CMC) experience high levels of stress and adverse mental health outcomes. Pediatric medical traumatic stress (PMTS) could be an important contributor that has not yet been explored. PMTS describes parents' reactions to their child's illness and medical treatment and can lead to post-traumatic stress symptoms. This is the first study to describe the experiences and impact of PMTS among parents of CMC.

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Serum biomarkers in prednisolone treated hand osteoarthritis patients.

To investigate whether biomarkers are modulated by prednisolone treatment in patients with hand osteoarthritis (OA) and whether they can predict response to prednisolone.

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Rapid titration with oral sustained-release morphine plus subcutaneous morphine in a multi-center, randomized control study of cancer patients with moderate to severe cancer pain.

Pain is one of the most common concomitant symptoms among cancer patients. Pharmacologic agents are regarded as a cornerstone of cancer pain management. 'Dose titration' with short-acting morphine is widely accepted. Such a titration method is very complicated. The analgesic background establishment is often delayed. Titration based on sustained-release opioids is also recommended, but the onset of analgesic effect requires hours, whereas the rescue analgesia is always needed. This study evaluated the optimized morphine titration scheme with a simultaneous combination of sustained-release morphine and subcutaneous morphine.

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Application of the novel Nalu™ Neurostimulation System for peripheral nerve stimulation.

Peripheral nerve stimulation is an established treatment modality for chronic neuropathic pain. Over the last decade, with the advent of innovative devices and delivery platforms, peripheral nerve stimulation has evolved from invasive open surgeries to image-guided, minimally invasive percutaneous procedures. The authors hereby present a novel device, the Nalu™ Neurostimulation System (Nalu Medical, CA, USA), which has established its advantages in providing predictable and reliable peripheral nerve stimulation therapy for chronic neuropathic pain management. This novel device is effective in treating chronic pain conditions such as post-herniorrhaphy pain syndrome, intercostal neuralgia, post-laminectomy syndrome, and complex regional pain syndrome and holds great promise for the treatment of peripheral neuropathic pain.

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Opioid Initiation and the Hazard of Falls or Fractures Among Older Adults with Varying Levels of Central Nervous System Depressant Burden.

Co-prescription of opioids with other central nervous system (CNS) depressants is common but the combination may increase the risk for adverse events such as falls and fractures, particularly among older adults. We explored the risk of fall- or fracture-related hospital visits after opioid initiation among older adults with varying degrees of concomitant CNS depressant burden.

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Chronic Migraine: A Narrative Review on the Use of Botulinum Toxin with Clinical Indications and Future Directions.

Chronic migraine belongs to the "chronic long-duration headaches", and it is associated to high burden and significant economic impact. Treatment for both episodic (EM) and chronic migraine (CM) is based on the management of acute attacks and their prevention. For moderate/severe attacks, pharmacological therapies are triptans, dihydroergotamine nasal sprays or injections or neuroleptics, non-steroidal anti-inflammatory drugs, and corticosteroids. Chronic migraine belongs to the "chronic long-duration headaches", and it is associated to high burden and significant economic impact. Treatment for both episodic (EM) and chronic migraine (CM) is based on the management of acute attacks and their prevention. For moderate/severe attacks, pharmacological therapies are triptans, dihydroergotamine nasal sprays or injections or neuroleptics, non-steroidal anti-inflammatory drugs, and corticosteroids. The pathophysiology of CM is characterized by an abnormal activation of the trigemino-vascular system in the meninges causing a neurogenic inflammation, which explains the use of anti-inflammatory during attacks. It seems that the objective of the preventive therapy with the botulin toxin OnaBoNT-A consists in interrupting the release of CGRP and other neuropeptides as well as the activation of C-fiber nociceptor and of the nearby A-delta fibers. The protocol for migraine treatment with OnaBoNT-A injections consists of 31-39 pericranial injection sites involving seven muscle groups bilaterally in specific areas of the head and neck, with a total dose of between 155 and 195 units, every three months. The severe adverse events reported with high doses of botulin toxin for spasticity, have not been reported for CM treated with OnabotA at the labeled dose. The established improvement with onabotulinumtoxinA treatment in CM patients had a positive impact not only in reduction monthly headache days but also in improving quality of life, with reduction in both healthcare resource utilisation (HRU) and work impairment. Aim of this review was to give an overview on the use of BoNT-A in patients with CM, giving practical advices on the clinical indications.

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Applying the Rapid OPPERA Algorithm to Predict Persistent Pain Outcomes among a Cohort of Women Undergoing Breast Cancer Surgery.

Persistent post-mastectomy pain after breast surgery is variable in duration and severity across patients, due in part to interindividual variability in pain processing. The Rapid OPPERA Algorithm (ROPA) empirically identified three clusters of patients with different risk of chronic pain based on four key psychophysical and psychosocial characteristics. We aimed to test this type of group-based clustering within in a perioperative cohort undergoing breast surgery to investigate differences in postsurgical pain outcomes. Women (N=228) scheduled for breast cancer surgery were prospectively enrolled in a longitudinal observational study. Pressure pain threshold (PPT), anxiety, depression, and somatization were assessed preoperatively. At 2-weeks, 3, 6, and 12-months after surgery, patients reported surgical area pain severity, impact of pain on cognitive/emotional and physical functioning, and pain catastrophizing. The ROPA clustering, which used patients' preoperative anxiety, depression, somatization, and PPT scores, assigned patients to three groups: Adaptive (low psychosocial scores, high PPT), Pain Sensitive (moderate psychosocial scores, low PPT), and Global Symptoms (high psychosocial scores, moderate PPT). The Global Symptoms cluster, compared to other clusters, reported significantly worse persistent pain outcomes following surgery. Findings suggest that patient characteristic-based clustering algorithms, like ROPA, may generalize across diverse diagnoses and clinical settings, indicating the importance of "person type" in understanding pain variability. Perspective: This article presents the practical translation of a previously developed patient clustering solution, based within a chronic pain cohort, to a perioperative cohort of women undergoing breast cancer surgery. Such preoperative characterization could potentially help clinicians apply personalized interventions based on predictions concerning postsurgical pain.

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Senolytic drugs relieve pain by reducing peripheral nociceptive signaling without modifying joint tissue damage in spontaneous osteoarthritis.

Aging is a risk factor for the development of osteoarthritis (OA), a progressive joint disease leading to cartilage damage, pain, and loss of function. In a mouse model of OA, senolytic drugs to selectively clear senescent cells (SnCs) that accumulate with injury or aging yielded a chondroprotective effect; however, this therapeutic benefit was limited in aged mice. Due to inconsistency between cartilage destruction and pain-associated symptoms, we studied the therapeutic effect of senolytics on joint pain in spontaneous OA. We orally treated 21- and 22-month old mice with an ABT263 and Dasatinib and Quercetin (D+Q) drug combination. Selective elimination of the SnCs that accumulated in the articular cartilage and synovium by these two drugs did not alter cartilage degeneration and abnormal bone changes during spontaneous OA progression. Treatment reduced thermal and mechanical hyperalgesia associated with OA and peripheral sensitization through decreased expression of axon guidance proteins (nerve growth factor NGF/TrkA) and nociceptive neuron (calcitonin gene-related peptide, CGRP) projection to the synovium, subchondral bone marrow, and dorsal root ganglion, and knee joint angiogenesis. Selective removal of the SnCs from cultures of synovial cells from human OA patients also decreased expression of senescent markers, axonal growth-promoting factors, such as NGF, and angiogenesis markers. We suggest that systemic administration of ABT263 and D+Q is an exciting therapeutic approach to age-related OA pain.

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Pain Allaying Epalrestat-Loaded Lipid Nanoformulation for the Diabetic Neuropathic Pain Interventions: Design, Development and Animal Study.

Diabetic peripheral neuropathy (DPN) is the most common complication of diabetes mellitus. Epalrestat, an aldose reductase inhibitor, has been approved for clinical therapy for diabetic peripheral neuropathic pain. In the present study, solid lipid-based nanoparticles are used for oral administration of epalrestat (E-SLN) and evaluated against diabetic neuropathic pain in a rat model.

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