Pain
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Sickle cell disease (SCD) is a chronic inflammatory disorder accompanied by chronic pain. In addition to ongoing pain and hyperalgesia, vaso-occlusive crises-induced pain can be chronic or episodic. Because analgesics typically used to treat pain are not very effective in SCD, opioids, including morphine, are a primary treatment for managing pain in SCD but are associated with many serious side effects, including constipation, tolerance, addiction, and respiratory depression. ⋯ Our results show that intraperitoneal administration of MCC22 produced exceptionally potent dose-dependent antihyperalgesia as compared to morphine, dramatically decreased evoked responses of nociceptive dorsal horn neurons, and decreased expression of proinflammatory cytokines in the spinal cord. Moreover, tolerance did not develop to its analgesic effects after repeated administration. In view of the extraordinary potency of MCC22 without tolerance, MCC22 and similar compounds may vastly improve the management of pain associated with SCD.
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Primary afferent sensory neurons are incredibly long cells, often traversing distances of over 1 m in humans. Cutaneous sensory stimuli are transduced in the periphery by specialised end organs or free nerve endings, which code the stimulus into electrical action potentials that propagate towards the central nervous system. Despite significant advances in our knowledge of sensory neuron physiology and ion channel expression, many commonly used techniques fail to accurately model the primary afferent neuron in its entirety. ⋯ We also demonstrate that capsaicin sensitivity is highly dependent on embryonic dissection age. This approach enables a comprehensive method to study the excitability and regional sensitivity of cultured sensory neurons on a single-cell level. Examination of the sensory terminals is crucial to further understand the properties and diversity of dorsal root ganglion sensory neurons.
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Meta Analysis
Quantitative sensory testing in patients with migraine: a systematic review and meta-analysis.
Quantitative sensory testing (QST) is widely used to assess somatosensory function by application of controlled stimuli across a variety of modalities. The aim of the present meta-analysis is to synthesize QST results across a wide array of studies of patients with migraine to identify the QST parameters that are reliably different between patients with migraine and healthy controls. In addition, we aimed to determine whether such differences vary according to stimulus location. ⋯ In addition, patients with migraine had higher pain ratings to cold suprathreshold stimuli for combined and nonlocal areas, and higher pain ratings to electrical suprathreshold stimuli for nonlocal areas. This meta-analysis indicates that the alterations in nociceptive processing of patients with migraine may be modality, measure, and location specific. These results provide researchers and clinicians the evidence to choose QST parameters optimally suited for differentiating patients with migraine and healthy controls.
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Randomized Controlled Trial Multicenter Study
Spinal manipulation and exercise for low back pain in adolescents: a randomized trial.
Low back pain (LBP) is common in adolescence, but there is a paucity of high-quality research to inform care. We conducted a multicenter randomized trial comparing 12 weeks of spinal manipulative therapy (SMT) combined with exercise therapy (ET) to ET alone. Participants were 185 adolescents aged 12 to 18 years with chronic LBP. ⋯ There were no serious treatment-related adverse events. For adolescents with chronic LBP, spinal manipulation combined with exercise was more effective than exercise alone over a 1-year period, with the largest differences occurring at 6 months. These findings warrant replication and evaluation of cost effectiveness.