Regional anesthesia and pain medicine
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Reg Anesth Pain Med · Jan 2019
ReviewImproving the therapeutic window of conventional opioids: novel differential signaling modulators.
Conventional opioids are widely used for acute pain management in the postoperative setting. However, a primary concern with conventional opioids is their therapeutic window-the range between doses that produce the desired therapeutic effect (analgesia) and doses that produce unwanted opioid-related adverse events (ORAEs). Conventional µ receptor opioids have a narrow therapeutic window in part because of their mechanism of action (MoA): they bind to µ receptors and non-selectively activate two intracellular signaling pathways, leading to analgesia and to ORAEs. ⋯ Agents with a 'differential signaling" MoA represent an innovative approach that may enhance the therapeutic window. These agents modulate µ receptor activity to selectively engage downstream signaling pathways associated with analgesia while limiting activity in downstream signaling pathways that lead to ORAEs. Differential signaling may fulfill an unmet need in the management of postoperative pain.
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Reg Anesth Pain Med · Jan 2019
Efficacy of the ketamine metabolite (2R,6R)-hydroxynorketamine in mice models of pain.
Ketamine has been shown to reduce chronic pain; however, the adverse events associated with ketamine makes it challenging for use outside of the perioperative setting. The ketamine metabolite (2R,6R)-hydroxynorketamine ((2R,6R)-HNK) has a therapeutic effect in mice models of depression, with minimal side effects. The objective of this study is to determine if (2R,6R)-HNK has efficacy in both acute and chronic mouse pain models. ⋯ This study demonstrates that (2R,6R)-HNK is superior to ketamine in reducing mechanical allodynia in acute and chronic pain models and suggests it may be a new non-opioid drug for future therapeutic studies.