Anesthesia and analgesia
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Anesthesia and analgesia · May 2009
The effect of amitriptyline on ectopic discharge of primary afferent fibers in the L5 dorsal root in a rat model of neuropathic pain.
The sodium channel blocker amitriptyline has been shown to inhibit ectopic discharge in injured nerves. In the present study, we characterized ectopic discharges of afferent fibers following L5/L6 spinal nerve ligation (SNL) by their electrophysiological properties and sensitivities to inhibition by amitriptyline in the decentralized L5 dorsal root in SNL rats. ⋯ These results provide direct evidence that amitriptyline, which is used clinically for the treatment of neuropathic pain, selectively inhibits ectopic discharge of low frequency and bursting discharge in the rat neuropathic pain model.
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Perioperative bleeding is a major challenge particularly because of increasing clinical use of potent antithrombotic drugs. Understanding current concepts of coagulation is important in determining the preoperative bleeding risk of patients, and in managing hemostatic therapy perioperatively. The serine protease thrombin plays pivotal roles in the activation of additional serine protease zymogens (inactive enzymatic precursors), cofactors, and cell-surface receptors. ⋯ However, a limitation of current treatment is that conventional clotting tests do not reflect the entire physiological processes of coagulation making optimal pharmacologic therapy difficult. Understanding the in vivo regulatory mechanisms and pharmacologic modulation of thrombin generation may help control bleeding without potentially increasing prothrombotic risks. In this review, we focus on the regulatory mechanisms of hemostasis and thrombin generation using multiple, simplified models of coagulation.