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KEY POINTS Low dose ketamine is a leading medication used to provide analgesia in pre-hospital and hospital settings. Low dose ketamine is increasingly used off-label to treat conditions such as depression. In animals, ketamine stimulates the sympathetic nervous system and increases blood pressure, but these physiological consequences have not been studied in conscious humans. Our data suggest that low dose ketamine administration blunts pain perception and reduces blood pressure, but not muscle sympathetic nerve activity burst frequency, responses during a cold pressor test in healthy humans. These mechanistic, physiological results inform risk-benefit analysis for clinicians administering low dose ketamine in humans. ABSTRACT Low dose ketamine is an effective analgesic medication. However, our knowledge of the effects of ketamine on autonomic cardiovascular regulation is primarily limited to animal experiments. Notably, it is unknown if low dose ketamine influences autonomic cardiovascular responses during painful stimuli in humans. We tested the hypothesis that low dose ketamine blunts perceived pain, and blunts subsequent sympathetic and cardiovascular responses during an experimental noxious stimulus. Twenty-two adults (10F/12M; 27 ± 6 years; 26 ± 3 kg m-2 , mean ± SD) completed this randomized, crossover, placebo-controlled trial during two laboratory visits. During each visit, participants completed cold pressor tests (CPT; hand in ∼0.4°C ice bath for 2 min) pre- and 5 min post-drug administration (20 mg ketamine or saline). We compared pain perception (100 mm visual analogue scale), muscle sympathetic nerve activity (MSNA; microneurography, 12 paired recordings), and beat-to-beat blood pressure (BP; photoplethysmography) during the pre- and post-drug CPTs separately using paired, two-tailed t tests. For the pre-drug CPT, perceived pain (P = 0.4378), MSNA burst frequency responses (P = 0.7375), and mean BP responses (P = 0.6457) were not different between trials. For the post-drug CPT, ketamine compared to placebo administration attenuated perceived pain (P

Multiple sclerosis (MS) is marked by conduction abnormalities within the central nervous system that can lead to impaired blood pressure regulation. However, the impact of this disease on dynamic neural control—responsiveness and timing (i.e., latency)—of blood pressure has not been examined. Utilizing a variable neck chamber system, we tested the hypothesis that patients with MS (MS: n=4) exhibit an altered response following baroreflex perturbation compared to sex and age matched healthy controls (CON: n=4). At rest, 5-sec pulses of neck suction (NS; -60 Torr) and neck pressure (NP; +40 Torr) were applied to simulate carotid hypertension and hypotension, respectively. Mean arterial pressure (MAP; Finometer) and heart rate (HR) were continuously measured in response to the perturbations. Carotid baroreflex (CBR) latencies (i.e., time-to-peak responses) were examined using carotid-cardiac (peak HR responses), carotid-vasomotor (peak MAP responses), and change in MAP at the peak HR response of the corresponding stimuli (MAP@HRpeak), all of which were not significant for both NP and NS. Following NS, responses in MAP (MS: -12±5, CON: -10±3 mmHg; p=0.43) and HR (MS: -9±3, CON: -8±4 BPM; p=0.58) were similar between groups. Following administration of NP, HR responses (MS: 4±2, CON: 5±4 BPM; p=0.47) were no different. However, the differences found in MAP were significant (MS: 5±2, CON: 8±2 mmHg; p=0.05), providing some evidence that baroreceptor responsiveness may be compromised when faced with a hypotensive challenge.

Impairments in sudomotor function during passive heat stress have been reported in multiple sclerosis (MS), a demyelinating disease of the CNS that disrupts autonomic function. However, little is k...

Treatment of (CO)5W[C(OCH3)C(CH3CH2] (1) with C2H5(CH3)2CONa in THF at −78°C followed by HCl produced: (CO)5W[C(OCH3)CH(CH3)CH2OC(CH3)2C2H5] (3) (1%), C2H5(CH3)2CO(CO)5W[C(OCH3)C(CH3)CH2]CH2C(CH3)CH(OCH3) (5) (