Pain
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A Cochrane review of ibuprofen in acute pain suggested that rapidly absorbed formulations of salts, or features to speed absorption, provided better analgesia than standard ibuprofen as the free acid. We examined several lines of evidence to investigate what benefit derived from fast-acting formulations. A systematic review of the kinetics of oral ibuprofen (30 studies, 1015 subjects) showed that median maximum plasma concentrations of fast-acting formulations occurred before 50 min (29-35 min for arginine, lysine, and sodium salts) compared with 90 min for standard formulations. ⋯ Fast-acting formulations of ibuprofen demonstrated more rapid absorption, faster initial pain reduction, good overall analgesia in more patients at the same dose, and probably longer-lasting analgesia, but with no higher rate of patients reporting adverse events. Achieving a better analgesic effect with fast-acting nonsteroidal anti-inflammatory drug formulations has important implications for safety. Formulation chemistry is of potential importance for analgesics.
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Cancer in bone is frequently a result of metastases from distant sites, particularly from the breast, lung, and prostate. Pain is a common and often severe pathological feature of cancers in bone, and is a significant impediment to the maintenance of quality of life of patients living with bone metastases. Cancer cell lines have been demonstrated to release significant amounts of the neurotransmitter and cell-signalling molecule l-glutamate via the system xC(-) cystine/glutamate antiporter. ⋯ Animals treated with sulfasalazine displayed reduced nociceptive behaviours and an extended time until the onset of behavioural evidence of pain. Animals treated with a lower dose of (S)-4-carboxyphenylglycine did not display this reduction in nociceptive behaviour. These results suggest that a reduction in glutamate secretion from cancers in bone with the system xC(-) inhibitor sulfasalazine may provide some benefit for treating the often severe and intractable pain associated with bone metastases.
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Idiopathic trigeminal neuralgia (TN) is classically associated with neurovascular compression (NVC) of the trigeminal nerve at the root entry zone (REZ), but NVC-induced structural alterations are not always apparent on conventional imaging. Previous studies report lower fractional anisotropy (FA) in the affected trigeminal nerves of TN patients using diffusion tensor imaging (DTI). However, it is not known if TN patients have trigeminal nerve abnormalities of mean, radial, or axial diffusivity (MD, RD, AD - metrics linked to neuroinflammation and edema) or brain white matter (WM) abnormalities. ⋯ These data indicate that TN patients have abnormal tissue microstructure in their affected trigeminal nerves, and as a possible consequence, WM microstructural alterations in the brain. These findings suggest that trigeminal nerve structural abnormalities occur in TN, even if not apparent on gross imaging. Furthermore, MD and RD findings suggest that neuroinflammation and edema may contribute to TN pathophysiology.