Anesthesia and analgesia
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Anesthesia and analgesia · Oct 2015
Development of Rapidly Metabolized and Ultra-Short-Acting Ketamine Analogs.
Ketamine is a well-established, rapidly acting dissociative anesthetic. Clinical use is limited by prolonged psychotomimetic phenomena on emergence, often requiring the coadministration of additional hypnotic drugs. We hypothesized that the development of ketamine ester analogs with ultrashort offset times might markedly reduce the dysphoric emergence phenomena and, hence, increase the utility of a ketamine-like hypnotic and analgesic. Here, we describe the results of studies that seek to define the pharmacology of 5 esters of ((1-(2-chlorophenyl)-2-oxocyclohexyl)amino)pentanoate hydrochloride, the first ketamine analogs designed to be susceptible to ultrarapid metabolism. ⋯ The 5 norketamine ester analogs retain the hypnotic characteristics of the parent compound, yet display rapid offset due to ultrarapid metabolism.
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Anesthesia and analgesia · Oct 2015
Stress Increases the Negative Effects of Chronic Pain on Hippocampal Neurogenesis.
Patients with chronic pain often suffer from affective disorders and cognitive decline, which significantly impairs their quality of life. In addition, many of these patients also experience stress unrelated to their illness, which can aggravate their symptoms. These nociceptive inputs are received by the hippocampus, in which maladaptive neuroplastic changes may occur in the conditions of chronic pain. The hippocampus is a structure involved in emotionality, learning, and memory, and the proliferating cells in the granular layer of the hippocampal dentate gyrus respond to chronic pain by slowing their turnover. However, whether the maturation, survival, and integration of newborn cells in the hippocampus are affected by chronic pain remains unclear. In addition, it is unknown whether an added stress may increase this effect. ⋯ Neuropathic pain negatively influences hippocampal neurogenesis (proliferation and survival), and this effect is exacerbated by stress. These neuroplastic changes may account for the affective and cognitive impairment seen in patients with chronic pain.