Browsing by Author "Metzler-Wilson, Kristen"

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    Effect of reflex and mechanical decreases in skin perfusion on thermal- and agonist-induced eccrine sweating in humans
    (American Physiological Society, 2023) Metzler-Wilson, Kristen; Fang, Milie M.; Alibegovic, Kenan; Daggett, James W.; Narra, Seetharam C.; Dazé, Robert P.; Miller, Olivia G.; Wilson, Thad E.; Physical Therapy, School of Health and Human Sciences
    In humans, skin blood flux (SkBF) and eccrine sweating are tightly coupled, suggesting common neural control and regulation. This study was designed to separate these two sympathetic nervous system end-organ responses via nonadrenergic SkBF-decreasing mechanical perturbations during heightened sudomotor drive. We induced sweating physiologically via whole body heat stress using a high-density tube-lined suit (protocol 1; 2 women, 4 men), and pharmacologically via forearm intradermal microdialysis of two steady-state doses of a cholinergic agonist, pilocarpine (protocol 2; 4 women, 3 men). During sweating induction, we decreased SkBF via three mechanical perturbations: arm and leg dependency to engage the cutaneous venoarteriolar response (CVAR), limb venous occlusion to engage the CVAR and decrease perfusion pressure, and limb arterial occlusion to cause ischemia. In protocol 1, heat stress increased arm cutaneous vascular conductance and forearm sweat rate (capacitance hygrometry). During heat stress, despite decreases in SkBF during each of the acute (3 min) mechanical perturbations, eccrine sweat rate was unaffected. During heat stress with extended (10 min) ischemia, sweat rate decreased. In protocol 2, both pilocarpine doses (ED50 and EMAX) increased SkBF and sweat rate. Each mechanical perturbation resulted in decreased SkBF but minimal changes in eccrine sweat rate. Taken together, these data indicate that a wide range of acute decreases in SkBF do not appear to proportionally decrease either physiologically- or pharmacologically induced eccrine sweating in peripheral skin. This preservation of evaporative cooling despite acutely decreased SkBF could have consequential impacts for heat storage and balance during changes in body posture, limb position, or blood flow restrictive conditions.
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    Effect of sensory blockade and rate of sensory stimulation on local heating induced axon reflex response in facial skin
    (Elsevier, 2021-07) Metzler-Wilson, Kristen; Wilson, Thad E.; Ausmus, Samantha M.; Sventeckis, Austin M.; Dermatology, School of Medicine
    Local neuronal circuits in non-glabrous skin drive the initial increase of the biphasic cutaneous vasodilation response to fast non-noxious heating. Voltage-sensitive Na+ (NaV) channel inhibition blocks the afferent limb of the non-glabrous forearm cutaneous axon reflex. Slow local heating does not engage this response. These mechanisms have not been adequately investigated or extended into areas associated with flushing pathology. We hypothesized that despite regional differences in sensory afferents, both sensory blockade and slowing the heating rate would abate the cutaneous axon reflex-mediated vasodilator responses in facial skin. We measured skin blood flow responses (laser-Doppler flowmetry) of 6 healthy subjects (5 female) to non-noxious forearm, cheek, and forehead local heating, expressed as a percentage of cutaneous vascular conductance at plateau (CVC = flux/mean arterial pressure). We assessed CVC during fast (1 °C/30s) and slow (1 °C/10 min) local heating to 43 °C in both NaV inhibition (topical 2.5% lidocaine/prilocaine) and control conditions. NaV inhibition decreased forearm (control: 84 ± 4, block: 34 ± 9%plateau, p < 0.001) and trended toward decreased forehead (control: 90 ± 3, block: 68 ± 3%plateau, p = 0.057) initial CVC peaks but did not alter cheek responses (control: 90 ± 3, block: 92 ± 13%plateau, p = 0.862) to fast heating. Slow heating eliminated the initial CVC peak incidence for all locations, and we observed similar results with combined slow heating and NaV inhibition. Slower sensory afferent activation rate eliminated the axon reflex response in facial and non-glabrous skin, but topical sensory blockade did not block axon reflex responses in flushing-prone cheek skin. Thus, slower heating protocols are needed to abate facial, particularly cheek, axon reflex responses.
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    Multifocal Transcranial Direct Current Stimulation to Modulate Motor Learning
    (2025-03) Greenwell, Davin Ross; Riley, Zachary; Kaleth, Anthony; Naugle, Kelly; Streepey, Jake; Metzler-Wilson, Kristen
    Transcranial direct current stimulation (tDCS) is a non-invasive brain stimulation technique that modulates neural excitability in targeted brain regions, influencing processes such as motor learning. While tDCS has been previously shown to benefit motor skill acquisition, much of this research has focused on relatively simple, unimanual tasks. Conversely, the effects of tDCS on more complex, bimanual motor tasks remain understudied, with existing findings often yielding mixed results. This inconsistency poses challenges for translating laboratory findings to functional, real-world motor skills, which frequently involve coordinated, two-handed movements and heightened cognitive demands. Emerging evidence suggests that multifocal tDCS paradigms, which simultaneously target multiple brain regions, may provide enhanced learning effects, particularly for complex motor tasks. Unlike traditional monofocal stimulation protocols that focus on the primary motor cortex (M1) or cerebellum individually, multifocal approaches may better address the neural dynamics underlying bimanual coordination and interhemispheric interactions. The purpose of this dissertation was to investigate the potential of multifocal tDCS to enhance motor learning in complex tasks, examining both unimanual and bimanual skill acquisition. This research involved a series of studies beginning with monofocal tDCS applied to M1 and the cerebellum during a non-dominant unimanual rhythm-timing task and culminating in a multifocal “tri-focal” stimulation protocol during a bimanual motor learning task. In Study One, we compared the effects of excitatory M1 stimulation against excitatory and inhibitory cerebellar and sham stimulation. While none of the monofocal tDCS conditions significantly enhanced learning compared to sham, small, non-significant trends were observed which informed the design of Study Two. Here, we observed that combining excitatory M1 stimulation with inhibitory cerebellar stimulation resulted in significant and robust improvements in motor learning. In Study Three, we found that bilateral M1 stimulation significantly enhanced the early stages of bimanual skill learning at lower intensities. However, Study Four revealed that increasing stimulation intensity or adding inhibitory cerebellar stimulation impaired bimanual learning. Together, these findings contribute to a growing understanding of how multifocal stimulation paradigms can be tailored to enhance motor learning in real-world tasks while underscoring the importance of carefully optimizing stimulation parameters to task-specific demands.
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    Role of Bradykinin Type 2 Receptors in Human Sweat Secretion: Translational Evidence Does Not Support a Functional Relationship
    (Karger, 2021-04) Wilson, Thad E.; Narra, Seetharam; Metzler-Wilson, Kristen; Schneider, Artur; Bullens, Kelsey A.; Holt, Ian S.; Physical Therapy, School of Health and Human Sciences
    Bradykinin increases skin blood flow via a cGMP mechanism but its role in sweating in vivo is unclear. There is a current need to translate cell culture and nonhuman paw pad studies into in vivo human preparations to test for therapeutic viability for disorders affecting sweat glands. Protocol 1: physiological sweating was induced in 10 healthy subjects via perfusing warm (46–48°C) water through a tube-lined suit while bradykinin type 2 receptor (B2R) antagonist (HOE-140; 40 μM) and only the vehicle (lactated Ringer’s) were perfused intradermally via microdialysis. Heat stress increased sweat rate (HOE-140 = +0.79 ± 0.12 and vehicle = +0.64 ± 0.10 mg/cm2/min), but no differences were noted with B2R antagonism. Protocol 2: pharmacological sweating was induced in 6 healthy subjects via intradermally perfusing pilocarpine (1.67 mg/mL) followed by the same B2R antagonist approach. Pilocarpine increased sweating (HOE-140 = +0.38 ± 0.16 and vehicle = +0.32 ± 0.12 mg/cm2/min); again no differences were observed with B2R antagonism. Last, 5 additional subjects were recruited for various control experiments which identified that a functional dose of HOE-140 was utilized and it was not sudorific during normothermic conditions. These data indicate B2R antagonists do not modulate physiologically or pharmacologically induced eccrine secretion volumes. Thus, B2R agonist/antagonist development as a potential therapeutic target for hypo- and hyperhidrosis appears unwarranted.
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    The Altered Vascular Endothelial Control of Facial Cutaneous Blood Flow in Rosacea
    (Medical Journals Sweden AB, 2025-04-27) Ungureanu, C. Ilinca; Kube, Megan J.; Wilson, Thad E.; Metzler-Wilson, Kristen; Anatomy, Cell Biology and Physiology, School of Medicine