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Oxidative Stress Contributes to Hyperalgesia in Osteoporotic Mice.

Chronic pain is one of the most common complications of postmenopausal osteoporosis. Since oxidative stress is involved in the pathogenesis of postmenopausal osteoporosis, we explored whether oxidative stress contributes to postmenopausal osteoporotic pain.

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Generalization of exposure in vivo in Complex Regional Pain Syndrome type I.

Exposure in vivo has been found successful in reducing pain-related fear, disability, and experienced pain in chronic pain patients. Despite the success of exposure treatment, experimental studies show that extinction learning is fragile, raising doubts whether extinction of pain-related fear generalizes to new threatening activities after treatment. This study examined whether a particular exposure treatment, in which patients are exposed to a variety of activities (Multiple Exposure condition), promotes generalization of extinction to new threatening situations, compared to an exposure treatment in which subjects are repeatedly exposed to the same set of activities (Repeated Exposure condition). Generalization tests were combined with randomized replicated single case experimental designs (N = 8). Included were patients with Complex Regional Pain Syndrome type I reporting elevated levels of pain-related fear. The Multiple Exposure treatment condition consisted of at least 15 activities to which patients were exposed once. The Repeated Exposure treatment condition exposed patients to only three activities during five sessions each. Generalization was tested by exposing patients to new fearful activities post-treatment and 6-months follow-up. Patients from both conditions performed equally well at both generalization tests. Daily measures showed that the Multiple Exposure condition is preferred to reduce fear of movement/(re)injury, pain catastrophizing and pain experience.

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Preclinical Neuropathic Pain Assessment; the Importance of Translatability and Bidirectional Research.

For patients suffering with chronic neuropathic pain the need for suitable novel therapies is imperative. Over recent years a contributing factor for the lack of development of new analgesics for neuropathic pain has been the mismatch of primary neuropathic pain assessment endpoints in preclinical vs. clinical trials. Despite continuous forward translation failures across diverse mechanisms, reflexive quantitative sensory testing remains the primary assessment endpoint for neuropathic pain and analgesia in animals. Restricting preclinical evaluation of pain and analgesia to exclusively reflexive outcomes is over simplified and can be argued not clinically relevant due to the continued lack of forward translation and failures in the clinic. The key to developing new analgesic treatments for neuropathic pain therefore lies in the development of clinically relevant endpoints that can translate preclinical animal results to human clinical trials. In this review we discuss this mismatch of primary neuropathic pain assessment endpoints, together with clinical and preclinical evidence that supports how bidirectional research is helping to validate new clinically relevant neuropathic pain assessment endpoints. Ethological behavioral endpoints such as burrowing and facial grimacing and objective measures such as electroencephalography provide improved translatability potential together with currently used quantitative sensory testing endpoints. By tailoring objective and subjective measures of neuropathic pain the translatability of new medicines for patients suffering with neuropathic pain will hopefully be improved.

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Impact of Opioid Consumption in Patients With Functional Gastrointestinal Disorders.

We aimed to determine the burden of opioid consumption in a cohort of patients with functional gastrointestinal disorders. All patients diagnosed with functional gastrointestinal disorders and referred to our university hospital were evaluated from 2013 to the beginning of 2019. Irritable bowel syndrome and functional dyspepsia diagnoses were determined according to Rome criteria and severity according to irritable bowel syndrome severity scoring system. Vomiting was quantified using a 5-point Likert scale, and constipation severity was measured using the Knowles-Eccersley-Scott-Symptom questionnaires. Quality of life was quantified by the GastroIntestinal Quality of Life Index. Patients were categorized as being treated on a chronic basis with either tramadol, step II opioids, step III opioids or as being opioid-free. 2933 consecutive patients were included. In our cohort, 12.5% had only irritable bowel syndrome, 39.3% had only functional dyspepsia, 24.9% had a combination of both, and 23.4% had other functional gastrointestinal disorders. Among them, the consumption of tramadol, step II (tramadol excluded) and step III opioids was 1.8, 1.3 and 0.3 % respectively in 2013 and 4.3, 3.4 and 1.9% in 2018 ( < 0.03). Opioid consumption was associated with increased vomiting ( = 0.0168), constipation ( < 0.0001), symptom severity ( < 0.001), more altered quality of life ( < 0.0001) and higher depression score ( = 0.0045). In functional gastrointestinal disorders, opioid consumption has increased in the last years and is associated with more GI symptoms (vomiting, constipation and GI severity), higher depression and more altered quality of life.

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Vagus Nerve Stimulation Transiently Mitigates Chemotherapy-Induced Peripheral Neuropathy in Rats.

Chemotherapy-induced peripheral neuropathy is a severe side effect of chemotherapeutic agents. Vagus nerve stimulation attenuates neuroinflammation by activating the cholinergic anti-inflammatory pathway and thus may attenuate CIPN.

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Intraarticular Injection of Infliximab-Loaded Thermosensitive Hydrogel Alleviates Pain and Protects Cartilage in Rheumatoid Arthritis.

Pain and cartilage destruction caused by rheumatoid arthritis (RA) are major challenges during clinical treatment. Traditional systemic administration not only has obvious side effects but also provides limited relief for local symptoms in major joints. Local delivery of therapeutics for RA treatment is a potential strategy but is limited by rapid intraarticular release.

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The Potential Contribution of Chronic Pain and Common Chronic Pain Conditions to Subsequent Cognitive Decline, New Onset Cognitive Impairment, and Incident Dementia: A Systematic Review and Conceptual Model for Future Research.

Growing evidence suggests that chronic pain and certain chronic pain conditions may increase risk for cognitive decline and dementia.

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The Prevalence of Migraine With Anxiety Among Genders.

The aims of the present systematic review were to explore the prevalence of migraine with anxiety exclusively and determine if and why there are likely to be differences across genders. Migraine is a very common neurological disorder and cause of productive disability worldwide that is more frequent in women of childbearing age than males. Previous studies have frequently demonstrated comorbidity of migraine and other psychiatric disorders. Although the prevalence of migraine across gender is well-established there are few if any systematic reviews on the prevalence of migraine comorbidity with anxiety cross-genders. The present systematic review included prevalence studies, clinic-based and cohort studies that reported the frequency of migraine with anxiety within the study sample. Eleven studies were included in the review after screening by two independent reviewers. Studies included participants who were 16 years and older diagnosed with migraine. The main findings of this review indicated that anxiety is a major comorbidity of migraine worldwide, with a wide range (16-83%) of prevalence and a mean of ~43% of patients experiencing comorbid symptoms. Subjective anxiety symptoms appear to be greater among males with migraine than females which could be attributable to both environmental and/or hormonal and genetic predispositions. The results reemphasize the high prevalence of migraine and comorbid anxiety symptoms worldwide while showing that although migraine is far more prevalent among women in general co-morbidity of migraine with anxiety unfolds a different gender difference. The results highlight the significance of exploring the impact of existing and pre-existing comorbid conditions of patients with migraines and further consideration into their diagnostic and treatment strategies.

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The Context Matters: A Retrospective Analysis of Life Stage at Chronic Pain Onset in Relation to Pain Characteristics and Psychosocial Outcomes.

Developmental life stage at chronic pain onset differs among chronic pain patients. Although pain affects multiple life domains, it is unknown whether the timing of chronic pain onset relates to pain characteristics and psychosocial outcomes. The purpose of this retrospective study was to investigate differences in pain characteristics and psychosocial outcomes in patients at different developmental life stages at chronic pain onset.

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Targeting migraine treatment with neuroimaging-Pharmacological neuroimaging in headaches.

The current review provides a recapitulation of recent advances in pharmacological neuroimaging in headache, a promising tool to understanding of how a drug works in the brain and how it may lead to new insights of disease mechanisms of headache.

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