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Radiosynthesis and Evaluation of a C-11 Radiotracer for Transient Receptor Potential Canonical 5 in the Brain.

TRPC5 belongs to the mammalian superfamily of transient receptor potential (TRP) Ca-permeable cationic channels and it has been implicated in various CNS disorders. As part of our ongoing interest in the development of a PET radiotracer for imaging TRPC5, herein, we explored the radiosynthesis, and in vitro and in vivo evaluation of a new C-11 radiotracer [C]HC070 in rodents and nonhuman primates.

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Responding flexibly to the complex problem of chronic pelvic pain: Incorporating patient needs into program development.

Chronic pelvic pain (CPP) in women is both common and disabling, and access to interdisciplinary care is limited. Patient education programs may represent a pragmatic approach to delivering interdisciplinary care, but to date the specific educational needs of patients with CPP are unknown.

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Psychological therapies for temporomandibular disorders (TMDs).

Temporomandibular disorders (TMDs) are a group of musculoskeletal disorders affecting the jaw. They are frequently associated with pain that can be difficult to manage and may become persistent (chronic). Psychological therapies aim to support people with TMDs to manage their pain, leading to reduced pain, disability and distress.

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Chronic pain as a blind spot in the diagnosis of a depressed society. On the implications of the connection between depression and chronic pain for interpretations of contemporary society.

One popular description of current society is that it is a depressed society and medical evidence about depression's prevalence may well make such an estimation plausible. However, such normative-critical assessments surrounding depression have to date usually operated with a one-sided understanding of depression. This understanding widely neglects the various ways depression manifests as well as its comorbidities. This becomes evident at the latest when considering one of depression's most prominent and well-known comorbidities: chronic pain. Against this background, we aim in this article to substantiate our leading claim that the phenomenal interconnection between depression and chronic pain must be acknowledged in the global diagnosis of a depressive society. Thus, we argue here for a complementation of the dominant interpretation of a depressed society. This would support the overcoming of oversimplified images and estimations about depression in current society and further, help to recognize chronic pain properly on the larger scale of assessments that address society as a whole.

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Roxadustat alleviates nitroglycerin-induced migraine in mice by regulating HIF-1α/NF-κB/inflammation pathway.

Sensitization of central pain and inflammatory pathways play essential roles in migraine, a primary neurobiological headache disorder. Since hypoxia-inducible factor-1α (HIF-1α) is implicated in neuroprotection and inflammation inhibition, herein we investigated the role of HIF-1α in migraine. A chronic migraine model was established in mice by repeated injection of nitroglycerin (10 mg/kg, i.p.) every other day for 5 total injections. In the prevention and acute experiments, roxadustat, a HIF-1α stabilizer, was orally administered starting before or after nitroglycerin injection, respectively. Pressure application measurement, and tail flick and light-aversive behaviour tests were performed to determine the pressure pain threshold, thermal nociceptive sensitivity and migraine-related light sensitivity. At the end of experiments, mouse serum samples and brain tissues were collected for analyses. We showed that roxadustat administration significantly attenuated nitroglycerin-induced basal hypersensitivity and acute hyperalgesia by improving central sensitization. Roxadustat administration also decreased inflammatory cytokine levels in serum and trigeminal nucleus caudalis (TNC) through NF-κB pathway. Consistent with the in vivo results showing that roxadustat inhibited microglia activation, roxadustat (2, 10, and 20 μM) dose-dependently reduced ROS generation and inflammation in LPS-stimulated BV-2 cells, a mouse microglia cell line, by inhibiting HIF-1α/NF-κB pathway. Taken together, this study demonstrates that roxadustat administration ameliorates migraine-like behaviours and inhibits central pain sensitization in nitroglycerin-injected mice, which is mainly mediated by HIF-1α/NF-κB/inflammation pathway, suggesting the potential of HIF-1α activators as therapeutics for migraine.

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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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