Pain
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Chronic postoperative pain hinders functional recovery after bone fracture and orthopedic surgery. Recently reported evidence indicates that caspase-6 is important in excitatory synaptic plasticity and pathological pain. Meanwhile, netrin-1 controls postsynaptic recruitment of α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid receptor (AMPAR) and synaptogenesis. ⋯ The reduction of fracture-mediated postoperative excitatory synaptic AMPAR current in the dorsal horn by caspase-6 inhibition was compromised by recombinant netrin-1. Exogenous caspase-6 induced pain hypersensitivity, reversing by netrin-1 knockdown or coapplication of NASPM. Thus, spinal caspase-6 modulation of GluA1-containing AMPAR activation and spine morphology through netrin-1 secretion is important in the development of fracture-related postsurgical pain in the mouse.
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Migraine is one of the top 5 most prevalent childhood diseases; however, effective treatment strategies for pediatric migraine are limited. For example, standard adult pharmaceutical therapies are less effective in children and can carry undesirable side effects. To develop more effective treatments, improved knowledge of the biology underlying pediatric migraine is necessary. ⋯ Lower GABA levels in the sensorimotor cortex were associated with being closer to their next migraine attack. Together, this indicates that GABA and glutamate disturbances occur early in migraine pathophysiology and emphasizes that evidence from adults with migraine cannot be immediately translated to pediatric sufferers. This highlights the need for further mechanistic studies of migraine in children, to aid in development of more effective treatments.
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Randomized Controlled Trial
Machine learning suggests sleep as a core factor in chronic pain.
Patients with chronic pain have complex pain profiles and associated problems. Subgroup analysis can help identify key problems. We used a data-based approach to define pain phenotypes and their most relevant associated problems in 320 patients undergoing tertiary pain management. ⋯ In addition, among 59 demographic, pain etiology, comorbidity, lifestyle, psychological, and treatment-related variables, sleep problems appeared 638 and 439 times among the most important characteristics in 1000 cross-validation runs where patients were assigned to the 2 extreme pain phenotype clusters. Also important were the parameters "fear of pain," "self-rated poor health," and "systolic blood pressure." Decision trees trained with this information assigned patients to the extreme pain phenotype with an accuracy of 67%. Machine learning suggested sleep problems as key factors in the most difficult pain presentations, therefore deserving priority in the treatment of chronic pain.