For the first time we obtained direct intra-neural measurements of muscle mass sympathetic nerve activity (MSNA) in relapsing-remitting multiple sclerosis (MS) individuals to test the hypothesis that spontaneous resting MSNA is reduced in MS individuals compared to age sex-matched healthy controls. MS-related symptoms that are known to effect the central nervous system (MS-DT/ST; n=5) and 3) healthy age and sex-matched settings (CON; n=6). Compared to the CON group MSNA burst rate of recurrence (bursts/min) was significantly reduced both MS-DT (P=0.027) and MS-DT/ST organizations (P=0.003). Similarly MSNA burst incidence (bursts/100 heart beats) was significantly reduced in both MS-DT (P=0.049) and MS-DT/ST groups (P=0.004) compared to the CON group. Burst rate of recurrence and burst incidence were not different between MS-DT and MS-DT/ST organizations. Resting plasma norepinephrine was also significantly reduced both MS-DT (P=0.039) and MS-DT/ST groups (P=0.021) compared to the CON group. Reduced MSNA may symbolize an important dysfunction in autonomic control of cardiovascular function in individuals with MS. Keywords: muscle mass sympathetic nerve activity autonomic dysfunction microneurography blood pressure plasma norepinephrine peripheral vasculature 1 Intro Multiple sclerosis (MS) offers been shown MP470 (MP-470) to impair autonomic control of cardiovascular function (Acevedo et al. 2000 Frontoni et al. 1996 Nasseri et al. 1998 Pentland and Ewing 1987 Sanya et al. 2005 and this dysfunction may increase with disease progression and increased medical disability (Flachenecker et al. 2001 Nasseri et al. 1998 Studies suggest that upwards of 50% of individuals with MS may experience symptoms of orthostatic dizziness (Flachenecker et al. 1999 Vita et al. 1993 Although impaired sympathetically-mediated vasomotor control has been suggested to be responsible for the symptoms of orthostatic dizziness observed in MS individuals (Flachenecker et al. 1999 Sanya et al. 2005 this has not been directly tested. Due to the obvious health-related issues of autonomic dysfunction in individuals with MS characterization of resting sympathetic outflow would provide a novel therapeutic target to alleviate symptoms associated with MS (dizziness light headedness thermal level of sensitivity etc.) Sympathetic outflow to vasculature supplying skeletal muscle mass or muscle mass sympathetic nerve activity (MSNA) can be recorded using microneurography (Vallbo et al. 1979 However to day no direct measurements of resting sympathetic neural function have been reported in individuals with MS. The MP470 (MP-470) goal of this investigation was to obtain direct intra-neural measurements of MSNA in MS individuals and to test the hypothesis that spontaneous resting MSNA is reduced in MS individuals compared to healthy control subjects. 2 METHODS 2.1 Human being Subjects Participants from the following three groups were investigated: 1) individuals with clinically certain relapsing remitting MS currently treated with disease modifying therapy only [MS-DT; n=6 (4 females 2 males); age=38±7 yrs; height=173±14 cm; excess weight=70±14 kg period from MS analysis=7±4 yrs]; 2) individuals with clinically certain relapsing-remitting MS MP470 (MP-470) MP470 (MP-470) currently on disease modifying therapy and medications for MS-related symptoms that are known to effect the central nervous system (we.e. anti-depressants psychostimulants anticonvulsants and anti-spasmatics) [MS-DT/ST; n=5 (4 females 1 male) age=38±7 yrs; height=166±8 cm; excess weight=59±11 kg period from MS analysis=8±4 yrs] and 3) healthy age and sex-matched settings [CON; n=6 (4 females 2 males); age=36±7 yrs; height=169±10 cm; excess weight=65±18 kg ]. MP470 (MP-470) Participants were normotensive (supine blood pressures <140/90 mmHg) and experienced MP470 (MP-470) no known cardiovascular disease. Subjects refrained from caffeine alcohol and rigorous exercise 24 h before the study. This study was authorized by the Institutional Review Table of the University or college of Texas Southwestern Rabbit Polyclonal to NT5E. Medical Center at Dallas. Participants offered educated written consent prior to screening. 2.2 Instrumentation and Protocol All experiments were performed at a constant ambient room heat (23-24 °C) with the subject in the supine position. Heart rate was monitored using ECG interfaced with a cardiotachometer (CWE Ardmore PA USA). Beat-by-beat blood pressure was measured by continuous finger cuff photoplethysmography (Finometer FMS.