Aim
Chronic stress exacerbates the symptoms of most pain disorders including interstitial cystitis/bladder pain syndrome (IC/BPS). Abnormalities in urothelial cells (UTC) occur in this debilitating ...bladder condition. The sequence of events that might link stress (presumably through increased sympathetic nervous system‐SNS activity) to urothelial dysfunction are unknown. Since autonomic dysregulation, mitochondrial dysfunction, and oxidative stress all occur in chronic pain, we investigated whether chronic psychological stress initiated a cascade linking these three dysfunctions.
Methods
Adult female Wistar Kyoto rats were exposed to 10 days of water avoidance stress (WAS). Bladders were then harvested for Western blot and single cell imaging in UTC cultures.
Results
UTC from WAS rats exhibited depolarized mitochondria membrane potential (Ψm ∼30% more depolarized compared to control), activated AMPK and altered UT mitochondria bioenergetics. Expression of the fusion protein mitofusion‐2 (MFN‐2) was upregulated in the mucosa, suggesting mitochondrial structural changes consistent with altered cellular metabolism. Intracellular calcium levels were elevated in cultured WAS UTC, consistent with impaired cellular function. Stimulation of cultured UTC with alpha‐adrenergic (α‐AR) receptor agonists increased reactive oxidative species (ROS) production, suggesting a direct action of SNS activity on UTC. Treatment of rats with guanethidine to block SNS activity prevented most of WAS‐induced changes.
Conclusions
Chronic stress results in persistent sympathetically mediated effects that alter UTC mitochondrial function. This may impact the urothelial barrier and signaling, which contributes to bladder dysfunction and pain. This is the first demonstration, to our knowledge, of a potential autonomic mechanism directly linking stress to mitochondrial dysfunction.
Postural orthostatic tachycardia syndrome (POTS) is a disabling condition characterized by orthostatic intolerance with tachycardia in the absence of drop-in blood pressure. A custom-built ...near-infrared spectroscopy device (NIRS) is applied to monitor the muscle oxygenation, noninvasively in patients undergoing incremental head-up tilt table (HUT). Subjects (6 POTS patients and 6 healthy controls) underwent 30
mins of 70∘ on a HUT. The results showed a significant difference in deoxyhemoglobin (Hb), change-in-oxygenation
(
Δ
Oxy
)
and blood volume
(
Δ
BV
)
between patients and healthy controls. However, oxyhemoglobin (HbO2) showed a significantly faster rate of change in the healthy controls during the first 10
mins of the tilt and during the recovery. This NIRS muscle oximetry tool provides quantitative measurements of blood oxygenation monitoring in diseases such as POTS.
Pure autonomic failure Kabir, M Ashish; Chelimsky, Thomas C
Handbook of clinical neurology,
2019, Letnik:
161
Journal Article
Recenzirano
In this chapter, we describe the history, presentation, diagnosis and treatment of pure autonomic failure (PAF). The pathology underlying this condition is thought to involve the deposition of alpha ...synuclein in the autonomic ganglia leading to diminished norepinephrine release and progressive autonomic dysfunction. We focus on various neurophysiological tests that may be used to evaluate the function of the peripheral autonomic nervous system including quantitative sudomotor axon reflex testing, thermoregulatory sweat testing, and others. These may help evaluate and diagnose various disorders of autonomic failure and neurogenic orthostatic hypotension including multiple system atrophy and Parkinson's disease dysautonomia. Management of PAF, including the therapeutic role of recent advances in pharmacologic treatment, is discussed.
Orthostatic hypotension (OH), a debilitating disorder characterized by a drop in blood pressure when in the upright position, may be treated through several pharmacologic and lifestyle modifications. ...The treatment is aimed at decreasing the symptoms, mainly the falls, increase the standing time, and improve the activities of daily life. A recent expert consensus outlined the management of orthostatic hypotension and included 4 sequential steps: 1) review medications and modify or remove those that may aggravate or cause OH; 2) non-pharmacologic measures; 3) pharmacologic measures and 4) treatment combinations. The aim of this manuscript is to review the non-pharmacological approach. In milder cases, this approach may suffice, but with more severe symptoms, such as falls, syncope or near-syncope, a pharmacological strategy is simultaneously employed. Furthermore, most non-pharmacological measures are combined. The non-pharmacological approach is aimed at optimizing blood volume, decreasing postural venous pooling, reducing heat and post-prandial induced vasodilation, emphasizing physical conditioning, and minimizing nocturnal diuresis.
Functional gastrointestinal disorders (FGIDs) are currently classified under the Rome criteria based on symptoms and absence of organic disease. Preliminary studies have shown that FGIDs are probably ...not restricted to the GI tract, but may represent a systemic disorder with comorbidities affecting other parts of the body, including migraine, fatigue, aches and pains, etc. The autonomic nervous system (ANS) provides the extrinsic control of GI motility, secretions, and even immune response. The role of the ANS in the development of FGIDs and comorbidities is still unclear. Limited data demonstrate orthostatic intolerance such as reflex syncope and postural tachycardia syndrome in a large subset of subjects with FGIDs. Some studies have found improvement in the GI symptoms with treatment of the orthostatic intolerance it produces. Prospective studies are needed to determine the chronology of the development of the comorbidities, the triggers that induce these syndromes, and effective treatments. This chapter aims to review current understanding of the role of the ANS in FGIDs.
•Comparison of PAG localization techniques on connectivity measures from rs-fMRI.•Measures of whole-brain connectivity depend on PAG localization technique.•Detection of potential disease-related ...differences depend on localization technique.
Previous studies examining the resting-state functional connectivity of the periaqueductal gray (PAG) in chronic visceral pain have localized PAG coordinates derived from BOLD responses to provoked acute pain. These coordinates appear to be several millimeters anterior of the anatomical location of the PAG. Therefore, we aimed to determine whether measures of PAG functional connectivity are sensitive to the localization technique, and if the localization approach has an impact on detecting disease-related differences in chronic visceral pain patients. We examined structural and resting-state functional MRI (rs-fMRI) images from 209 participants in the Multidisciplinary Approach to the Study of Chronic Pelvic Pain (MAPP) Research Network study. We applied three different localization techniques to define a region-of-interest (ROI) for the PAG: 1) a ROI previously-published as a Montreal Neurological Institute (MNI) coordinate surrounded by a 3 mm radius sphere (MNI-sphere), 2) a ROI that was hand-traced over the PAG in a MNI template brain (MNI-trace), and 3) a ROI that was hand-drawn over the PAG in structural images from 30 individual participants (participant-trace). We compared the correlation among the rs-fMRI signals from these PAG ROIs, as well as the functional connectivity of these ROIs with the whole brain. First, we found important non-uniformities in brainstem rs-fMRI signals, as rs-fMRI signals from the MNI-trace ROI were significantly more similar to the participant-trace ROI than to the MNI-sphere ROI. We then found that choice of ROI also impacts whole-brain functional connectivity, as measures of PAG functional connectivity throughout the brain were more similar between MNI-trace and participant-trace compared to MNI-sphere and participant-trace. Finally, we found that ROI choice impacts detection of disease-related differences, as functional connectivity differences between pelvic pain patients and healthy controls were much more apparent using the MNI-trace ROI compared to the MNI-sphere ROI. These results indicate that the ROI used to localize the PAG is critical, especially when examining brain functional connectivity changes in chronic visceral pain patients.
Abdominal migraines present with debilitating symptoms in adolescence. At our institution, the gastroenterology, neurology, and autonomic departments collaborated in treating patients with such ...presentations. This case series describes 6 patients who were given intravenous dihydroergotamine (DHE) for presumed abdominal migraines. DHE was only used when other agents like amitriptyline, verapamil, topiramate, or depakote had proved ineffective. DHE was started at 0.5 mg dose and on average 7 to 9 mg were given on each hospitalization. Patient ages ranged from 13 to 19 years with the majority being female. One patient did not respond to treatment. One patient was admitted 4 times for symptoms of abdominal migraines resolving with DHE. The average time between symptom relapse was about 5 to 12 months. Five of our 6 patients responded to the infusion without significant side effects. Based on these case series, DHE may be a treatment option in children with intractable abdominal migraine.
Introduction
Autonomic testing is used clinically. Yet, the prevalence of “abnormal” variants in the healthy population has not been reported.
Results
We report the results of autonomic testing in ...healthy females >18 years, in whom we found decrease or absent sudomotor function in 1–2 locations.
Conclusions
These findings should caution physicians in the interpretation of autonomic testing. This report underscores the need of larger studies to determine the prevalence of these findings.
Objective. To describe the reasons for referral, autonomic diagnoses, test results, and patient management in a large pediatric population referred for testing for an autonomic disorder. Design. The ...authors reviewed autonomic testing data and medical records for patients aged 18 years and younger who underwent testing between 1993 and 2007 and who had adequate clinical data. Relevance of test results to clinical symptoms was ranked on a 3-point scale. Treatments were noted and their benefit ranked on a 5-point scale. Results. Among 142 pediatric patients identified, postural tachycardia syndrome was most common (71%) while orthostatic hypotension was rare (5%). Testing provided relevant information regarding the patient’s symptoms in 88% of the cases. Beta-blockers were the most commonly prescribed medication (59%); 73% improved. Conclusions. Postural tachycardia syndrome was common in this large pediatric population, whereas orthostatic hypotension was infrequent. The symptomatic improvement in the majority bears an unclear relationship to treatment. Prospective studies are needed.
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