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Pain in neurodegenerative diseases with atypical parkinsonism: a systematic review on prevalence, clinical presentation, and findings from experimental studies.

Parkinson's disease-related pain has increasingly been investigated in research studies. Still, only a few studies have addressed the prevalence and clinical characteristics of pain in neurodegenerative disorders with atypical parkinsonism. The existing evidence, although scarce, suggests that, similarly as in Parkinson's disease, individuals with neurodegenerative diseases with atypical parkinsonism might be predisposed to the development of persistent pain. Today, as the global population is aging and we face an epidemic of neurodegenerative disorders, under-treated pain is taking a great toll on an ever-rising number of people. Here, we provide an up-to-date review of the current knowledge on the prevalence of pain, its clinical features, and findings from experimental studies that might signpost altered pain processing in the most prevalent neurodegenerative disorders with atypical parkinsonism: multiple system atrophy, progressive supranuclear palsy, corticobasal syndrome, frontotemporal dementia, and dementia with Lewy bodies. Finally, we point out the current gaps and unmet needs that future research studies should focus on. Large-scale, high-quality clinical trials, coupled with pre-clinical research, are urgently needed to reveal the exact pathophysiological mechanisms underpinning heightened pain and pave the path for mechanistically-driven analgesic interventions to be developed, ultimately leading to an improvement in the quality of life of individuals with neurodegenerative disorders.

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Glutamate in primary afferents is required for itch transmission.

Whether glutamate or itch-selective neurotransmitters are used to confer itch specificity is still under debate. We focused on an itch-selective population of primary afferents expressing MRGPRA3, which highly expresses Vglut2 and the neuropeptide neuromedin B (Nmb), to investigate this question. Optogenetic stimulation of MRGPRA3 afferents triggers scratching and other itch-related avoidance behaviors. Using a combination of optogenetics, spinal cord slice recordings, Vglut2 conditional knockout mice, and behavior assays, we showed that glutamate is essential for MRGPRA3 afferents to transmit itch. We further demonstrated that MRGPRA3 afferents form monosynaptic connections with both NMBR and NMBR neurons and that NMB and glutamate together can enhance the activity of NMBR spinal DH neurons. Moreover, Nmb in MRGPRA3 afferents and NMBR DH neurons are required for chloroquine-induced scratching. Together, our results establish a new model in which glutamate is an essential neurotransmitter in primary afferents for itch transmission, whereas NMB signaling enhances its activities.

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Family History of Alcohol Use Disorder as a Predictor of Endogenous Pain Modulation Among Moderate to Heavy Drinkers.

Family history of alcohol use disorder (AUD) is frequently endorsed by persons with chronic pain. Although individuals with a family history of AUD have demonstrated enhanced sensitivity to painful stimulation, previous research has not examined endogenous pain modulation in this population. The goal of this study was to test family history of AUD as a predictor of conditioned pain modulation, offset analgesia, and temporal summation among a sample of moderate and heavy drinkers. Adults with no current pain (N = 235; 58.3% male; M = 34.3; 91.9% non-Hispanic; 60% white) were evaluated for family history of AUD at baseline and pain modulatory outcomes were assessed via quantitative sensory testing. Participants with a family history of AUD (relative to those without) evinced a pro-nociceptive pain modulation profile in response to experimental pain. Specifically, family history of AUD was associated with deficits in pain-inhibitory processes. Approximately 4% of the variance in endogenous pain modulation was accounted for by family history, and exploratory analyses suggested these effects may be driven by paternal AUD.

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Arguments for and against a new diagnostic entity for patients with chronic pain on long-term opioid therapy for whom harms outweigh benefits.

The goal of this study was to understand perspectives on whether a new diagnostic entity, distinct from Diagnostic and Statistical Manual – 5 (DSM-5) opioid use disorder (OUD), is needed for patients with chronic pain on long-term opioid therapy (LTOT) for whom the harms of continued opioid therapy outweigh the benefits. Data were collected as part of a larger Delphi study. We used rapid and thematic qualitative methods to analyze data from 51 panelists with expertise in internal medicine, psychiatry, psychology, and related fields. Three-quarters of panelists supported a new diagnostic entity; common themes included recognizing distinct experiences of patients prescribed LTOT, addressing problems with DSM-5 OUD criteria, facilitating research and improved treatment, and reducing stigma. Thirteen panelists opposed the creation of a new diagnostic entity; common themes included similarities in biological underpinnings of patients prescribed LTOT and diagnosed with OUD, belief that the continuum of OUD captured patients' experiences, finding better ways to address problems with DSM-5 OUD criteria, and concerns about stigma. While this expert panel disagreed about the need for a new diagnostic entity, there was an overall acknowledgement that the current implementation of DSM-5's OUD diagnosis is not meeting the needs of LTOT providers or patients. Perspective: The DSM-5's OUD diagnosis may not adequately meet the needs of patients on LTOT for whom the harms of continued opioid therapy outweigh the benefits. Experts do not agree on how to address this problem; more work is needed to determine if a new diagnostic entity would be beneficial.

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Prevalence of trigeminal neuralgia in multiple sclerosis: A systematic review and meta-analysis.

The prevalence of Trigeminal Neuralgia (TN) in patients diagnosed with multiple sclerosis (MS) is insufficiently understood and controversially reported. This study focused on providing a better understanding of the prevalence of TN in MS patients.

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Butyric acid modulates periodontal nociception in Porphyromonas gingivalis-induced periodontitis.

Periodontitis progresses with chronic inflammation, without periodontal pain. However, the underlying mechanisms are not well known. Here, the involvement of butyric acid (BA) in periodontal pain sensitivity in Porphyromonas gingivalis (P. gingivalis)-induced periodontitis was examined.

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Chronic Pain Clinical and Prescriptive Practices in the Cannabis Era.

To explore how health care providers in the United States are adapting clinical recommendations and prescriptive practices in response to patient use of medical cannabis (MC) for chronic pain symptoms.

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Remote Delivery of the Chronic Pain Self-management Program Using Self-directed Materials and Small-group Telephone Support: A Pilot Study.

A remote (telephone and tool kit) chronic pain program was studied using the RE-AIM (reach, effectiveness, adoption, implementation, and maintenance) framework. This 6-week pilot took place in underserved communities in Cleveland, Ohio. We determined reach by the diversity of the population, nearly 50% Black and mostly low income. Effectiveness over 7 weeks was shown with validated instruments (depression, pain, sleep, quality of life, self-rated health, and self-efficacy). Changes in pain, depression, and self-efficacy were significant. ( < .01). Remote implementation was accomplished by sending participants a box of materials (book, exercise and relaxation CDs, a self-test, and tip sheets). Participants also participated in peer-facilitated weekly scripted telephone calls. Maintenance was demonstrated as the study site has offered nine additional programs with more plan. In addition, 60 additional organizations are now offering the program. This proof-of-concept study offers an alternate to in-person chronic pain self-management program delivery.

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Altered brain activity in end-stage knee osteoarthritis revealed by resting-state functional magnetic resonance imaging.

Knee osteoarthritis (KOA) is characterized by a degenerative change of knee cartilage and secondary bone hyperplasia, resulting in pain, stiffness, and abnormal walking gait. Long-term chronic pain causes considerable cortical plasticity alternations in patients. However, the brain structural and functional alterations associated with the pathological changes in knee joints of end-stage KOA patients remain unclear. This study aimed to analyze the structural and functional connectivity alterations in end-stage KOA to comprehensively understand the main brain-associated mechanisms underlying its development and progression.

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Prolactin signaling modulates stress-induced behavioral responses in a preclinical mouse model of migraine.

The aim of this study was to determine if prolactin signaling modulates stress-induced behavioral responses in a preclinical migraine model.

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