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Impact of abuse on migraine-related sensory hypersensitivity symptoms: Results from the American Registry for Migraine Research.

Prior studies have established an association between a history of abuse and the development of migraine. This cross-sectional observational study explored the relationship between self-reported abuse history with migraine-related sensory hypersensitivity symptoms.

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A Role for Transmembrane Protein 16C/Slack Impairment in Excitatory Nociceptive Synaptic Plasticity in the Pathogenesis of Remifentanil-induced Hyperalgesia in Rats.

Remifentanil is widely used to control intraoperative pain. However, its analgesic effect is limited by the generation of postoperative hyperalgesia. In this study, we investigated whether the impairment of transmembrane protein 16C (TMEM16C)/Slack is required for α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic receptor (AMPAR) activation in remifentanil-induced postoperative hyperalgesia. Remifentanil anesthesia reduced the paw withdrawal threshold from 2 h to 48 h postoperatively, with a decrease in the expression of TMEM16C and Slack in the dorsal root ganglia (DRG) and spinal cord. Knockdown of TMEM16C in the DRG reduced the expression of Slack and elevated the basal peripheral sensitivity and AMPAR expression and function. Overexpression of TMEM16C in the DRG impaired remifentanil-induced ERK1/2 phosphorylation and behavioral hyperalgesia. AMPAR-mediated current and neuronal excitability were downregulated by TMEM16C overexpression in the spinal cord. Taken together, these findings suggest that TMEM16C/Slack regulation of excitatory synaptic plasticity via GluA1-containing AMPARs is critical in the pathogenesis of remifentanil-induced postoperative hyperalgesia in rats.

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A Pilot Study of a Chronic Pain Self-Management Program Delivered by Community Health Workers to Underserved African American Older Adults.

African American older adults living in disadvantaged communities are disproportionately burdened by disabling pain. To address their needs, we tested the feasibility and potential effects of a cognitive-behavioral chronic pain self-management program delivered by community health workers.

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Mechanisms, diagnosis, prevention and management of perioperative opioid-induced hyperalgesia.

Opioid-induced hyperalgesia (OIH) occurs when opioids paradoxically enhance the pain they are prescribed to ameliorate. To address a lack of perioperative awareness, we present an educational review of clinically relevant aspects of the disorder. Although the mechanisms of OIH are thought to primarily involve medullary descending pathways, it is likely multifactorial with several relevant therapeutic targets. We provide a suggested clinical definition and directions for clinical differentiation of OIH from other diagnoses, as this may be confusing but is germane to appropriate management. Finally, we discuss prevention including patient education and analgesic management choices. As prevention may serve as the best treatment, patient risk factors, opioid mitigation, and both pharmacologic and non-pharmacologic strategies are discussed.

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Nox4-Dependent Upregulation of S100A4 after Peripheral Nerve Injury Modulates Neuropathic Pain Processing.

Previous studies suggested that reactive oxygen species (ROS) produced by NADPH oxidase 4 (Nox4) affect the processing of neuropathic pain. However, mechanisms underlying Nox4-dependent pain signaling are incompletely understood. In this study, we aimed to identify novel Nox4 downstream interactors in the nociceptive system. Mice lacking Nox4 specifically in sensory neurons were generated by crossing Advillin-Cre mice with Nox4 mice. Tissue-specific deletion of Nox4 in sensory neurons considerably reduced mechanical hypersensitivity and neuronal action potential firing after peripheral nerve injury. Using a proteomic approach, we detected various proteins that are regulated in a Nox4-dependent manner after injury, including the small calcium-binding protein S100A4. Immunofluorescence staining and western blot experiments confirmed that S100A4 expression is massively up-regulated in peripheral nerves and dorsal root ganglia after injury. Furthermore, mice lacking S100A4 showed increased mechanical hypersensitivity after peripheral nerve injury and after delivery of a ROS donor. Our findings suggest that S100A4 expression is up-regulated after peripheral nerve injury in a Nox4-dependent manner and that deletion of S100A4 leads to an increased neuropathic pain hypersensitivity.

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Early Management of OnabotulinumtoxinA Treatment in Chronic Migraine: Insights from a Real-Life European Multicenter Study.

OnabotulinumtoxinA (BT-A) quarterly was the first treatment approved specifically for chronic migraine (CM). It is unclear whether three cycles are better than two to assess early BT-A response.

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Amylin analog pramlintide induces migraine-like attacks in patients.

Migraine is a prevalent and disabling neurological disease. Its genesis is poorly understood and there remains unmet clinical need. We aimed to identify mechanisms and thus novel therapeutic targets for migraine using human models of migraine and translational models in animals, with emphasis on amylin, a close relative of calcitonin gene-related peptide (CGRP).

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Associations of Coexisting Pain and Fatigue Severity with Physical Performance and Quality of Life among Middle-Aged and Older Individuals with Chronic Knee Pain: A randomized controlled trial.

To examine associations of combined pain and fatigue severity with physical performance and quality of life in people with chronic knee pain.

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Opening of ATP sensitive potassium channels causes migraine attacks with aura.

Migraine afflicts more than one billion individuals worldwide and is a leading cause of years lived with disability. In about a third of individuals with migraine aura occur in relation to migraine headache. The common pathophysiological mechanisms underlying migraine headache and migraine aura are yet to be identified. Based on recent data, we hypothesized that levcromakalim, an ATP-sensitive potassium channel opener, would trigger migraine attacks with aura in migraine with aura patients.

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Differential risk of falls associated with pain medication among community-dwelling older adults by cognitive status.

Persons living with dementia have an elevated risk of falling and chronic pain. This study investigates the relationship of pain medication use with falls among community-dwelling adults based on their cognitive status.

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