Anesthesia and analgesia
-
Anesthesia and analgesia · Oct 2015
Several Ryanodine Receptor Type 1 Gene Mutations of p.Arg2508 Are Potential Sources of Malignant Hyperthermia.
Malignant hyperthermia (MH) is a pharmacogenetic disorder that occurs in predisposed individuals after exposure to volatile anesthetics or depolarizing muscle relaxants. Genetic mutations of ryanodine receptor 1 (RYR1), which are considered to cause MH, are found mainly in 3 regions called "hotspots." There are sometimes multiple mutations at the same site of RYR1. Although p.Arg2508 of RYR1 is located outside hotspots, several mutations or variants (including the known MH causative mutation p.Arg2508Cys) have been identified in this region. We hypothesized that any mutations or variants in RYR1 p.Arg2508 cause important changes in pathological conditions related to MH. In this study, we analyzed the functions of 4 different RYR1 variants containing mutations at p.Arg2508. ⋯ Any of these 4 mutations in RYR1 p.Arg2508 may cause important changes related to MH. Studying the effects of changes in amino acids at 2508 in RYR1 on the movement of this large protein may lead to a better understanding of the pathology of MH events.
-
Anesthesia and analgesia · Oct 2015
First Human Study of the Investigational Sedative and Anesthetic Drug AZD3043: A Dose-Escalation Trial to Assess the Safety, Pharmacokinetics, and Efficacy of a 30-Minute Infusion in Healthy Male Volunteers.
AZD3043 is a positive allosteric modulator of the γ-aminobutyric acid type A receptor that is rapidly metabolized to an inactive metabolite by esterases present in blood and liver. Preclinical results suggest that AZD3043 has the potential as a short-acting IV sedative/anesthetic drug with rapid and predictable recovery characteristics and a favorable safety and tolerability profile. ⋯ AZD3043 was well tolerated in this first human study and seems to exhibit rapid onset and recovery, indicating potential use as a short-acting drug for anesthesia and sedation.
-
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.
-
Anesthesia and analgesia · Oct 2015
Contralateral Hyperalgesia from Injection of Endothelin-1 into the Ipsilateral Paw Requires Efferent Conduction into the Contralateral Paw.
Contralateral hyperalgesia, occurring after unilateral injury, is usually explained by central sensitization in spinal cord and brain. We previously reported that injection of endothelin-1 (ET-1) into one rat hindpaw induces prolonged mechanical and chemical sensitization of the contralateral hindpaw. Here, we examined the role of contralateral efferent activity in this process. ⋯ These results show that efferent transmission through the contralateral innervation into the paw is necessary for contralateral sensitization by ET-1, suggesting that the release of substances by distal nerve endings is involved. The release of substances in the periphery is essential for contralateral sensitization by ET-1 and may also contribute to secondary hyperalgesia, occurring at loci distant from the primary injury, that occurs after surgery or nerve damage.
-
Anesthesia and analgesia · Oct 2015
Editorial"You Live Life Going Forwards and Understand It Looking Backwards!" The Sixtieth Anniversary of the World Federation of Societies of Anaesthesiologists: 60 Years of Cooperation Between the International Anesthesia Research Society and the World Federation of Societies of Anaesthesiologists.