Dexmedetomidine is a highly specific, potent and selective a 2 -adrenoceptor agonist. Although intrathecal and epidural administration of dexmedetomidine has been found to produce analgesia, whether this analgesia results from an effect on spinal cord substantia gelatinosa (SG) neurons remains unclear. Here, we investigated the effects of dexmedetomidine on postsynaptic transmission in SG neurons of rat spinal cord slices using the whole-cell patch-clamp technique. In 92% of the SG neurons examined (n = 84), bathapplied dexmedetomidine induced outward currents at )70 mV in a concentration-dependent manner, with the value of effective concentration producing a half-maximal response (0.62 lm). The outward currents induced by dexmedetomidine were suppressed by the a 2 -adrenoceptor antagonist yohimbine, but not by prazosin, an a 1 -, a 2B -and a 2C -adrenoceptor antagonist. Moreover, the dexmedetomidine-induced currents were partially suppressed by the a 2C -adrenoceptor antagonist JP-1302, while simultaneous application of JP-1302 and the a 2A -adrenoceptor antagonist BRL44408 abolished the current completely. The action of dexmedetomidine was mimicked by the a 2A -adrenoceptor agonist oxymetazoline. Plots of the current-voltage relationship revealed a reversal potential at around )86 mV. Dexmedetomidine-induced currents were blocked by the addition of GDP-b-S [guanosine-5¢-O-(2-thiodiphosphate)] or Cs + to the pipette solution. These findings suggest that dexmedetomidine hyperpolarizes the membrane potentials of SG neurons by G-protein-mediated activation of K + channels through a 2A -and a 2C -adrenoceptors. This action of dexmedetomidine might contribute, at least in part, to its antinociceptive action in the spinal cord.

Background Bioelectrical impedance analysis (BIA)‐derived phase angle is expected to be an efficient prognostic marker of health adverse events with aging as an alternative of muscle mass. We aimed to examine the predictive ability of phase angle for incident disability in community‐dwelling elderly and determine the optimal cut‐off values. Methods Community‐dwelling elderly aged ≥65 years (n = 4452; mean age = 71.8 ± 5.3 years, 48.3% women) without disability at baseline participated in this prospective cohort study. Phase angle and appendicular skeletal muscle mass (ASM) were examined using a multi‐frequency BIA at baseline. Other potential confounding factors (demographics, cognitive function, depressive symptoms, medications, and physical performance) were also assessed. Incident disability was monitored on the basis of long‐term care insurance certification. Results Over a follow‐up of 24 months, 4.0% (n = 174) experienced disability, with an overall incidence rate of 20.6 per 1000 person‐years. The Cox hazard regression analysis showed that phase angle, as a continuous variable, was independently associated with incident disability after adjusting the covariates [male: hazard ratios (HRs) = 0.61, 95% confidence interval (CI) = 0.37–0.98; female: HR = 0.58, 95% CI = 0.37–0.90], although body mass index adjusted ASM was not. Receiver operating characteristic analysis indicated moderate predictive abilities of phase angle for incident disability [male: area under the receiver operating characteristic curve (AUC) = 0.76, 95% CI = 0.70–0.83; female: AUC = 0.71, 95% CI = 0.65–0.76], while those of body mass index adjusted ASM were low (male: AUC = 0.59, 95% CI = 0.521–0.66; female: AUC = 0.58, 95% CI = 0.52–0.63). Multivariate Cox regression analysis showed that low phase angle categorized by cut‐off value (male, ≤4.95°; female, ≤4.35°) was independently related to increased risk of incident disability (HR = 1.95, 95% CI = 1.37–2.78). Conclusions Lower phase angle independently predicts the incident disability separately from known risk factors. BIA‐derived phase angle can be used as a valuable and simple prognostic tool to identify the elderly at risk of disability as targets of preventive treatment.

[Purpose] During exercise, skeletal muscle motor units are recruited based on afferent sensory input following peripheral metabolic by-product accumulation. The purpose of this study was to investigate whether lactate plays a role in conveying fatigue-related information to the brain. [Subjects] Eleven healthy adults participated in this study. [Methods] Subjects performed handgrip exercises at 10%, 30%, and 50% maximal voluntary contraction for 120 s. They were monitored for brachial artery blood pressure, respiratory quotient, muscle fatigue (integrated electromyogram, median power frequency), blood lactate levels, muscle blood flow, and brain activity. [Results] The handgrip exercise protocol caused significant muscle fatigue based on 28% and 37% reductions in median power frequency detected at 30% and 50% maximal voluntary contraction, respectively. Subjects exhibited intensity-dependent increases in blood pressure, respiratory quotient, muscle blood flow, and circulating lactate concentrations. Furthermore, brain activity increased at 30% and 50% maximal voluntary contraction. Multiple regression analysis identified muscle blood flow at 30% maximal voluntary contraction and lactate at 50% maximal voluntary contraction with standardized partial regression coefficients of −0.64 and 0.75, respectively. [Conclusion] These data suggest that blood lactate concentration and muscle blood flow, which reflect muscle metabolism, may convey load intensity information to the brain during muscle fatigue.

Background Malnutrition plays an essential role in the mechanism of pathogenesis for sarcopenia. In late life, both food consumption and energy intakes decline. One of key factors for reduced energy intakes is anorexia of ageing. The aim of this study is to examine the association between anorexia of ageing and sarcopenia among community-dwelling elderly Japanese individuals. Methods This uses population-based, cross-sectional cohort study of elderly Japanese individuals. Anorexia of ageing was assessed via a simplified nutritional appetite questionnaire. Handgrip strength and walking speed were tested, and skeletal muscle mass was assessed using a bio-impedance analysis device. Subjects with sarcopenia were defined as those who met the criteria of the Asian Working Group for Sarcopenia. The association between anorexia of ageing and sarcopenia was then analysed via multiple regression analysis. Results In total, 9,496 elderly Japanese individuals were evaluated (mean age 74.1 ± 5.4 years; male, 47.0%). The prevalence of anorexia of ageing was 9.8% (n = 927) in the present study. The prevalence of sarcopenia in men was 1.

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Background Identifying factors that contribute to the development of sarcopenia in older adults is a public health priority. Although several studies have examined the association between sleep duration and sarcopenia, additional evidence is needed to reveal the causality of this association, especially from a longitudinal study. The purpose of the present study was to examine whether sleep duration was associated with the progression to sarcopenia and its subcomponents among community‐dwelling older adults in Japan. Methods A total of 3918 older community‐dwelling people (mean age: 73.2 ± 6.0 years, 51.8% female) included in the National Center for Geriatrics and Gerontology Study of Geriatric Syndromes were analysed. Sleep duration was assessed using a self‐reported questionnaire. Logistic regression analysis was used to estimate the odds ratios (ORs) and 95% confidence intervals (CIs) of progression of sarcopenia at Wave 2 (4 years later), according to the three categories of sleep duration [short: ≤6.0 h, medium: 6.1–8.9 h (control), & long: ≥9.0 h)] at Wave 1. Results The numbers in each group in the second wave among the total sample were as follows: short 403 (10.3%), medium 2877 (73.4%), and long 638 (16.3%). Significant associations with the progression of sarcopenia were found in the long sleep duration group compared with the medium one, even after adjustment for other covariates (OR 1.66, 95% CI: 1.02–2.69, P = 0.040). Long sleep duration was significantly associated with slow gait (OR: 1.55, 95% CI: 1.17–2.06, P = 0.002) and low grip strength (OR: 1.34, 95% CI: 1.00–1.78, P = 0.047) but was not associated with low muscle mass (OR: 1.33, 95% CI: 0.74–2.38, P = 0.343). Conclusions This study revealed that long sleep duration was associated with an increased risk of progression to sarcopenia among older adults.