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Background and Purpose: Centers for training in autonomic nervous system (ANS) disorders are not widely available and the recent coronavirus 2019 pandemic temporarily reduced training opportunities in autonomic medicine across European countries. Here we evaluated the current state of education, clinical skills and postgraduate educational preferences on ANS disorders of European neurology residents and consultants., Methods: A 23-item questionnaire was developed and distributed online amongst European neurology residents and consultants via mailing lists of the European Academy of Neurology. The questions assessed demographics, current training opportunities and learning preferences in ANS disorders. Six multiple-choice questions were used to self-evaluate knowledge of ANS disorders., Results: In all, 285 individuals answered the survey (60% female, mostly 25-34 years of age). All respondents considered clinical autonomic skills necessary for good clinical neurological practice, and 92% would like to increase their ANS knowledge. Female respondents and those who trained in Southern/Eastern/Greater Europe more frequently judged ANS skills important for clinical practice than male respondents (p = 0.012) and respondents from Northern/Western Europe (p = 0.011). Female and younger respondents felt less confident in managing ANS disorders (p = 0.001 and p < 0.001, respectively). Respondents below 45 years of age (p < 0.001) and those with lower confidence in managing ANS disorders (p = 0.004) were more likely to recommend that ANS education is embedded in the residency curriculum., Conclusions: Most European neurology residents and consultants reported a need for more autonomic education, with additional gender, age and regional differences. These findings underscore the importance of increasing the educational content on autonomic medicine in European medical and postgraduate curricula., (© 2024 The Author(s). European Journal of Neurology published by John Wiley & Sons Ltd on behalf of European Academy of Neurology.)

Background: It is increasingly significant that adults with diabetes experience lower urinary tract symptoms, however, there has been limited research in younger individuals with type 1 diabetes., Objective: To investigate bladder function using non-invasive urodynamics as a potential indicator of autonomic neuropathy in adolescents with type 1 diabetes. This involved examining the association between urinary flow disturbances, reported symptoms, and results from other autonomic tests., Study Design: Cross-sectional study enrolling 49 adolescents with type 1 diabetes and 18 control subjects. All participants underwent uroflowmetry and ultrasound scanning, completed the Composite Autonomic Symptom Score (COMPASS)-31 questionnaire, and were instructed to record their morning urine volume and voiding frequencies and report them back. Cardiovascular reflex tests (CARTs) and the quantitative sudomotor axon reflex test (QSART) were performed., Results: The main results are shown in the Summary figure., Discussion: In this study, urological abnormalities were not significantly more frequent in adolescents with diabetes, however, urological issues were observed. This is supported by previous findings of Szabo et al. who found that adolescents with type 1 diabetes had reduced flow acceleration and time to maximum flow compared to control subjects. In our study, we observed cases with reduced acceleration and prolonged uroflow curves, possibly indicating detrusor underactivity. People with diabetes had a higher risk of nocturia than healthy controls, which our results supported. Some adolescents reported urination twice per night. Based on these findings, it is considered beneficial to ask about urological symptoms annually to determine if more examinations (frequency-volume charts and uroflowmetry) are necessary and/or if any opportunities for treatment optimization exist. However, uroflowmetry has limitations, as bladder filling and emptying is a complex process involving multiple pathways and neurological centers, making it difficult to standardize and evaluate. Another limitation of this study was that our control group was smaller and consisted of fewer males than females, which could affect the results due to differences in anatomy and physiology in the lower urinary tract system., Conclusion: In conclusion, adolescents with type 1 diabetes, as well as healthy adolescents, frequently experience urological symptoms. Although urological abnormalities were not significantly more frequent in adolescents with diabetes in this study, the focus on nocturia and risk for bladder dysfunction seems relevant, even in adolescents without any other tests indicating autonomic dysfunction., Competing Interests: Conflict of interest No potential conflicts are relevant to this article., (Copyright © 2024 The Author(s). Published by Elsevier Ltd.. All rights reserved.)

Neurosarcoidosis is a rare and serious condition. Rapid diagnosis and treatment are crucial to prevent morbidity and mortality. When neurological symptoms are not present at the time of diagnosis, CNS involvement can be undetected. We present a case of neurosarcoidosis complicating Löfgren's syndrome and discus the challenges in diagnostics and treatment, that can be encountered.

Purpose: To quantify sweat gland nerve fiber density in adolescents with diabetes. Additionally, to investigate associations between sudomotor innervation, sweat responses, and possible risk factors for sudomotor neuropathy., Methods: Cross-sectional study where 60 adolescents with type 1 diabetes (duration > 5 years) and 23 control subjects were included. Clinical data, quantitative sudomotor axon reflex test, and skin biopsies were obtained. Skin tissue was immunostained and imaged by confocal microscopy. Quantification of the sweat gland volume and three-dimensional reconstruction of the nerve fibers was performed using a design-unbiased technique., Results: Adolescents with diabetes had a significant reduction of maximum and mean values of nerve fiber length and nerve fiber density in sweat glands compared to controls (p values < 0.05). No association between nerve fiber density and sweat responses was found (p = 0.21). In cases with reduced sweat gland nerve fiber length, nerve fiber density, and volume, the sweat response was reduced or absent. Height, systolic blood pressure, time in hypoglycemia, and total daily and basal/total insulin dose were positively correlated to sweat response, while low-density lipoprotein, and HbA1c were negatively correlated with sweat response (p values < 0.05). Other microvascular complications and high cholesterol levels increased the relative risk for reduced sweat gland nerve fiber density., Conclusion: Our findings of reduced sweat gland innervation in a selected group of adolescents add new knowledge about the structural changes that occur in autonomic nerves due to diabetes. Evaluating both the sweat gland innervation and sweat gland volume was important for understanding the association with sweat responses. Further research is needed to understand its clinical relevance., (© 2023. The Author(s).)

Aims: To estimate the prevalence of large fiber (LFN), small fiber (SFN), and autonomic neuropathy in adolescents with type 1 diabetes using confirmatory tests known from adults and to identify risk factors and bedside methods for neuropathy., Methods: Sixty adolescents with type 1 diabetes (diabetes duration > five years) and 23 control subjects underwent neurological examination and confirmatory diagnostic tests for neuropathy, including nerve conduction studies, skin biopsies determining intraepidermal nerve fiber density, quantitative sudomotor axon reflex test (QSART), cardiovascular reflex tests (CARTs), and tilt table test. Possible risk factors were analyzed. Bedside tests (biothesiometry, DPNCheck®, Sudoscan, and Vagus®device) were compared with the confirmatory tests using ROC analysis., Results: The prevalence of neuropathies in the adolescents with diabetes (mean HbA1c 7.6% (60 mmol/mol)) was as follows: 14% confirmed/26% subclinical LFN, 2% confirmed/25% subclinical SFN, 20% abnormal QSART, 8% abnormal CARTs, and 14% orthostatic hypotension. Higher age, higher insulin dose, previous smoking, and higher triglycerides level were found to increase the relative risk for neuropathy. The bedside tests showed poor to acceptable concordance with the confirmatory tests (all, AUC ≤ 0.75)., Conclusions: The diagnostic tests confirmed the presence of neuropathy in adolescents with diabetes and underscore the importance of prevention and screening., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023. Published by Elsevier B.V.)

Background: To assess the prevalence of objective signs of gastrointestinal (GI) autonomic neuropathy (AN) in adolescents with type 1 diabetes (T1D). In addition, to investigate associations between objective GI findings and self-reported symptoms or other findings of AN., Methods: Fifty adolescents with T1D and 20 healthy adolescents were examined with a wireless motility capsule to assess the total and regional GI transit times and motility index. GI symptoms were evaluated with the GI Symptom Rating Scale questionnaire. AN was evaluated with cardiovascular and quantitative sudomotor axon reflex tests., Results: There was no difference in GI transit times in adolescents with T1D and healthy controls. Adolescents with T1D had a higher colonic motility index and peak pressure than the controls, and GI symptoms were associated with low gastric and colonic motility index (all p < 0.05). Abnormal gastric motility was associated with the duration of T1D, while a low colonic motility index was inversely associated with "time in target range" for blood glucose (all p < 0.01). No associations were found between signs of GI neuropathy and other measures of AN., Conclusions: Objective signs of GI neuropathy are common in adolescents with T1D and it seems to require early interventions in patients at high risk of developing GI neuropathy.

Most frequently, complex regional pain syndrome (CRPS) develops after a trauma and affects distal parts of the limbs. Early recognition and initiation of adequate treatment is crucial for a favorable outcome. On the other hand, misdiagnosing other disorders as CRPS is detrimental because more appropriate treatment may be withheld from the patients. Despite intensive research, a specific biomarker or paraclinical measure for CRPS diagnosis is still lacking. Instead, clinical criteria approved by the International Association for the Study of Pain (IASP) and latest adapted in 2019 are central for diagnosing CPRS. Thus, the CRPS diagnosis remains challenging with the risk of a "deliberate diagnosis" for unexplained pain, while at the same time a delayed CRPS diagnosis prevents early treatment and full recovery. CRPS is a diagnosis of exclusion. To clinically diagnose CRPS, a vigorous exclusion of "other diseases that would better explain the signs and symptoms" are needed before the patients should be referred to tertiary centers for specific pain treatment. We highlight red flags that suggest "non-CRPS" limb pain despite clinical similarity to CRPS. Clinical and neurological examination and paraclinical evaluation of a probably CRPS patient are summarized. Finally, we pinpoint common differential diagnoses for CRPS. This perspective might help CRPS researchers and caregivers to reach a correct diagnosis and choose the right treatment, regardless whether for CRPS mimics or CRPS itself., Competing Interests: The authors report no conflicts of interest in this work., (© 2022 Terkelsen and Birklein.)

Aims: To estimate the prevalence of neuropathy in adolescents with type 1 diabetes., Methods: Systematic collection of published studies exploring the prevalence of large fibre neuropathy (LFN), small fibre neuropathy (SFN), and autonomic neuropathy in adolescents with type 1 diabetes. Following prospective registration (Prospero CRD42020206093), PubMed, EMBASE, and Cochrane Library were searched for studies from 2000 to 2020. PICO framework was used in the selection process (Population: adolescents aged 10-19 years with type 1 diabetes; Intervention: diagnostic methods for neuropathy; Comparison: reference data; Outcome: data on prevalence or comparison). Data were extracted concerning study quality based on available data and established methods for determining and diagnosing various neuropathy types., Results: From 2,017 initial citations, 27 studies (7589 participants) fulfilled eligibility criteria. The study population (47% males) had a diabetes duration between 4.0 and 10.6 years, and HbA1c level between 7.3 and 10.8%, 56-95 mmol/mol. The prevalence of LFN, based on nerve conduction studies, was 10-57%. Based on other tests for neuropathy, the prevalence of LFN and SFN was 12-62%, and that of cardiac autonomic neuropathy was 12-75%., Conclusion: The described prevalence of neuropathy in adolescents with type 1 diabetes varied, which can be methodological due to different screening methods and classifications of neuropathy., (Copyright © 2021 The Authors. Published by Elsevier Inc. All rights reserved.)

Background: Complex regional pain syndrome (CRPS) is a debilitating pain condition often resistant to standard treatment modalities. In these cases, spinal cord stimulation (SCS) can be an option, but the effect on CRPS remains disputed. We aimed to assess the long-term effect of SCS on CRPS., Methods: We retrospectively analysed 51 CRPS patients implanted with an SCS system at the University Hospitals in Aarhus or Odense, Denmark, with a median follow-up time of 4.4 years. Primary outcomes were pain intensity on a numeric rating scale (NRS) and the Patients' Global Impression of Change (PGIC). Secondary outcomes were patient satisfaction, work status, consumption of pain medication, the Major Depression Inventory (MDI), Pain Catastrophizing Scale (PCS) and quality of life (QoL) measured using the Short-Form Health Survey (SF-36). For each outcome measure, baseline data were compared to the latest collected data point., Results: A significant pain relief was found with a mean reduction in NRS score of 2.4 (95% CI: 1.7-3.0, p < 0.0001). 68.8% reported 'much improved' or 'very much improved' on the PGIC scale. 87.5% would choose SCS again for the same outcome. A significant beneficial impact was found on MDI score, PCS, SF-36 summary scores and consumption of tricyclic antidepressants, antiepileptic drugs and opioids. No statistical effect was found on work status., Conclusion: Pain intensity, depression, pain catastrophizing, pain medication use and QoL were significantly improved after SCS implantation, with high patient satisfaction rates in CRPS patients. This study supports the continued use of SCS in the treatment of severe CRPS., Significance: This study presents detailed data from a large, well-characterized cohort of Danish CRPS patients treated with SCS, analyzing several outcome measures. The results serve to document SCS as an effective treatment for severe CRPS and expands the cumulative level of evidence in favor of its use. Additionally, analysis of preoperative patient characteristics suggests that SCS treatment should not be withheld in patients with a high degree of psychological distress or high consumption of analgesics., (© 2021 European Pain Federation - EFIC®.)

Neuronal aggregates of misfolded alpha-synuclein protein are found in the brain and periphery of patients with Parkinson's disease. Braak and colleagues have hypothesized that the initial formation of misfolded alpha-synuclein may start in the gut, and then spread to the brain via peripheral autonomic nerves hereby affecting several organs, including the heart and intestine. Age is considered the greatest risk factor for Parkinson's disease, but the effect of age on the formation of pathology and its propagation has not been studied in detail. We aimed to investigate whether propagation of alpha-synuclein pathology from the gut to the brain is more efficient in old versus young wild-type rats, upon gastrointestinal injection of aggregated alpha-synuclein. Our results demonstrate a robust age-dependent gut-to-brain and brain-to-gut spread of alpha-synuclein pathology along the sympathetic and parasympathetic nerves, resulting in age-dependent dysfunction of the heart and stomach, as observed in patients with Parkinson's disease. Moreover, alpha-synuclein pathology is more densely packed and resistant to enzymatic digestion in old rats, indicating an age-dependent maturation of alpha-synuclein aggregates. Our study is the first to provide a detailed investigation of alpha-synuclein pathology in several organs within one animal model, including the brain, skin, heart, intestine, spinal cord and autonomic ganglia. Taken together, our findings suggest that age is a crucial factor for alpha-synuclein aggregation and complete propagation to heart, stomach and skin, similar to patients. Given that age is the greatest risk factor for human Parkinson's disease, it seems likely that older experimental animals will yield the most relevant and reliable findings. These results have important implications for future research to optimize diagnostics and therapeutics in Parkinson's disease and other age-associated synucleinopathies. Increased emphasis should be placed on using aged animals in preclinical studies and to elucidate the nature of age-dependent interactions., (© The Author(s) (2021). Published by Oxford University Press on behalf of the Guarantors of Brain.)

Treatment-induced neuropathy of diabetes is an iatrogenic acute painful sensory and autonomic neuropathy. The condition is caused by rapid downregulation of blood glucose after a long period of hyperglycaemia. In this case report, a 43-year-old man with Type 1 diabetes and severe metabolic dysregulation had downregulated his blood glucose level with 3.8% over ten weeks through optimised insulin treatment and weight loss. He developed severe neuropathic pain due to small fiber neuropathy and neurogenic autonomic dysfunction with erectile dysfunction, urine retention and cardiovagal and enteric dysfunction.

Introduction: The Composite Autonomic Symptom Score (COMPASS 31) is a validated self-assessment questionnaire quantifying the severity and distribution of autonomic symptoms across six domains (orthostatic intolerance, vasomotor, secretomotor, gastrointestinal, bladder and pupillomotor functions) by scoring 31 clinically selected questions. The aim of this study was to translate into Danish and validate the Danish version of COMPASS 31., Methods: The original (US) English version of the COMPASS 31 questionnaire was translated into Danish via forward/backward translation and validated in accordance with a protocol set forth by the Autonomic Group at the Mayo Clinic. Ten healthy controls and 20 patients with disorders associated with a variable degree of autonomic dysfunction were enrolled - all bilingual (Danish mother tongue, proficiency in English)., Results: A total of 20 patients (16 women, aged 48 + 17 years) and ten healthy controls (six women, aged 40 + 19 years) were included. Test-retest reliability was high with no consistent bias, and the Danish version of the COMPASS 31 significantly correlated with the English version of the COMPASS 31 in both total score and all sub-scores. Patients scored significantly higher on the COMPASS 31 questionnaire than healthy controls (34.0 (26.5-49.2) versus 2.3 (1.6-24.3) (median (interquartile ranges); p = 0.01)., Conclusions: We present a Danish version of the COMPASS 31 - a validated self-reported questionnaire allowing for the quantification of autonomic dysfunction. We hope this Danish version will be implemented in both clinical practice and research settings in Denmark., Funding: none., Trial Registration: not relevant., (Articles published in the DMJ are “open access”. This means that the articles are distributed under the terms of the Creative Commons Attribution Non-commercial License, which permits any non-commercial use, distribution, and reproduction in any medium, provided the original author(s) and source are credited.)

Background: Patients with Parkinson's disease (PD) often show peripheral autonomic dysfunction and depositions of pathological alpha-synuclein aggregates in the skin. However, functional consequences of this skin involvement have received little attention., Objective: To determine thermographic differences in the skin between healthy controls (HCs) and PD patients on hands, feet, and trunk and to correlate findings with symptoms and signs of dysautonomia. Between-group differences in autonomic parameters and questionnaires were explored., Methods: Twenty-one PD patients and 19 HCs were examined by thermographic infrared imaging of standardized anatomical locations on the trunk and upper and lower extremities at baseline and after exposure to cold stress test (CST). Thermal recovery rates (RRs) were determined on the basis of thermograms. Correlation analyses between alterations in skin temperature and autonomic dysfunction were performed., Results: The most significant RR difference between PD patients and HCs was seen on the fifth distal phalanx 10 minutes post-CST (mean RR ± SD: 51 ± 18% vs. 70 ± 23%, p  = 0.003). No between-group differences were seen in baseline or post-CST values of the feet. No correlations were seen between thermal parameters and clinical and autonomic data. In the HC group, a positive, moderate correlation was seen between post-CST recovery values on the 3 rd and 5 th phalanx and body mass index (BMI) ( r  = 0.661, p  = 0.002)., Conclusions: The PD patients exhibited significant reduction in RR compared to HC and patients also displayed altered thermal responses in multiple anatomical locations. Thus, infrared thermography could become an important future tool in investigation of autonomic deficiency in PD., Competing Interests: The authors declare that they have no conflicts of interest., (Copyright © 2020 Mathias Møller Purup et al.)

Aims: To investigate the region-specific effects of painful trigeminal capsaicin stimulation in healthy participants., Methods: Twenty healthy participants (10 men and 10 women) participated in four sessions in which they received application of 0.05 mL Vaseline (placebo) or capsaicin cream (0.1%) to a different area innervated by the three branches of the trigeminal nerve: the supraorbital area (V1), the nasal mucosa (V1/V2), and the maxillary (V2) and mandibular (V3) oral mucosa. The participants rated their perceived sensations on a 0-50-100 numeric rating scale (NRS). Thermal (5°C, 23°C, and 50°C) and mechanical (32 mN and 256 mN) sensitivities were assessed. The Schirmer tearing test was used to monitor the lacrimation level as a local measure of autonomic activity, and the Task Force Monitor was used to record systemic autonomic activity. Data were analyzed using repeated measures analysis of variance., Results: Capsaicin application evoked significantly higher overall NRS scores (P < .001) and induced significantly higher ratings to the heat stimuli (P < .009) in all sessions compared to control. For lacrimation level, capsaicin stimulation resulted in a significant increase compared to control (P < .0002) only in the nasal mucosa session., Conclusion: Topical application of capsaicin cream to the different branches of the trigeminal nerve caused higher NRS scores along with an altered somatosensory sensitivity. Furthermore, in the nasal mucosa session, a robust local and generalized parasympathetic activation appeared following capsaicin application.

Introduction: In this study we assessed the value of genetic screening for Fabry disease (FD) and hereditary ATTR amyloidosis in patients with idiopathic small-fiber neuropathy (SFN) or mixed neuropathy in a clinical setting., Methods: This was a Nordic multicenter study with 9 participating centers. Patients with idiopathic SFN or mixed neuropathy were included. Genetic sequencing of the TTR and GLA genes was performed., Results: There were 172 patients enrolled in the study. Genetic screening was performed in 155 patients. No pathogenic mutations in the TTR gene were found. A single patient had a possible pathogenic variant, R118C, in the GLA gene, but clinical investigation showed no firm signs of FD., Discussion: Screening for hereditary ATTR amyloidosis and FD in patients with idiopathic SFN or mixed neuropathy without any additional disease-specific symptoms or clinical characteristics in a Nordic population appears to be of little value in a clinical setting. Muscle Nerve 59:354-357, 2019., (© 2018 Wiley Periodicals, Inc.)

Neurogenic autonomic dysfunction (NAD) is underdiagnosed, and it is likely in patients, who have orthostatic hypotension and symptoms from multiple organ systems as well as abnormal results from a neurological examination. A clinical and neurophysiological examination of the autonomic nervous system combined with a standardised paraclinical evaluation should be performed. NAD may be present in neurodegenerative disorders, vitamin deficiency, toxicity, infection, and in paraneoplastic, metabolic, hereditary and immune-mediated conditions.

Background: The deep breathing test (DB) and Valsalva maneuver (VM) are used to detect autonomic dysfunction. The VM induces sympathetically mediated changes in blood pressure (phase II late, phase IV, and recovery time) and both tests induce vagally mediated heart rate changes. There is limited information on effects of key variables, compliance with testing and the effects of non-compliance This study has twin goals of evaluating compliance with standard instructions and the effects of changes in key variables. We also evaluated the effect of position on the VM., Material and Methods: Forty healthy males performed DB at air exchange volumes of 50, 80, and 100% of vital lung capacity (VLC). The VM was performed at 40 and 30mmHg expiratory pressure for 15 and 10s in sitting and supine position, respectively., Results: Participants performed DB at lower volumes than intended and were not able to maintain 100% VLC for the duration of the test. The DB heart rate response decreased 6.3beats/min per liter below VLC. During the VM, subjects blew at lower pressures than instructed. The VM responses were significantly larger with longer expiration durations, higher expiratory pressures and when performed sitting. Performing the VM at 40mmHg for 10s in supine position increased the odds ratio of experiencing flat-top responses., Conclusion: The ability of subjects to strictly comply with methodological guidelines significantly improves results. Recording of both test parameters and ensuing results is suggested., (Copyright © 2017 Elsevier B.V. All rights reserved.)

Although the use of prayer as a religious coping strategy is widespread and often claimed to have positive effects on physical disorders including pain, it has never been tested in a controlled experimental setting whether prayer has a pain relieving effect. Religious beliefs and practices are complex phenomena and the use of prayer may be mediated by general psychological factors known to be related to the pain experience, such as expectations, desire for pain relief, and anxiety. Twenty religious and twenty non-religious healthy volunteers were exposed to painful electrical stimulation during internal prayer to God, a secular contrast condition, and a pain-only control condition. Subjects rated expected pain intensity levels, desire for pain relief, and anxiety before each trial and pain intensity and pain unpleasantness immediately after on mechanical visual analogue scales. Autonomic and cardiovascular measures provided continuous non-invasive objective means for assessing the potential analgesic effects of prayer. Prayer reduced pain intensity by 34 % and pain unpleasantness by 38 % for religious participants, but not for non-religious participants. For religious participants, expectancy and desire predicted 56-64 % of the variance in pain intensity scores, but for non-religious participants, only expectancy was significantly predictive of pain intensity (65-73 %). Conversely, prayer-induced reduction in pain intensity and pain unpleasantness were not followed by autonomic and cardiovascular changes.

Aims: To investigate in a randomized, double-blinded, placebo controlled, crossover study the effect of a single dose of the nonselective β-adrenergic receptor antagonist propranolol (40 mg) on hypertonic saline (HS)-evoked masseter muscle pain and autonomic activity during rest and during a mental arithmetic task (Paced Auditory Serial Addition Task, PASAT)., Methods: Sixteen healthy women participated in two sessions in which propranolol or placebo was administered orally prior to two 5-minute infusions (30 minutes apart) of HS in the masseter muscle. The second HS infusion was combined with PASAT. HS-evoked pain intensity was scored on a numeric rating scale (NRS, 0 to 10). Heart rate variability and hemodynamic measures were recorded noninvasively (Task Force Monitor). Data were analyzed with repeated measurements analysis of variance (ANOVA)., Results: Propranolol did not reduce NRS pain scores compared with placebo but did induce significant autonomic changes with reduced heart rate and increased heart rate variability (standard deviations of all normal RR intervals; root mean square successive differences; low-frequency power; high-frequency power; and total power) independent of the mental task., Conclusion: A single dose of propranolol had no effect on acute HS-evoked pain levels during rest or during mental arousal. However, it influenced the tone of the autonomic nervous system, possibly reflecting an anxiolytic effect.

Aims: To test in a randomized controlled trial, if hypertonic saline (HS)-evoked pain and autonomic function are modulated by either a cold pressor test (CPT) or mental arithmetic stress induced by a paced auditory serial addition task (PASAT)., Methods: Fourteen healthy women participated in three sessions. Pain was induced by two 5% HS infusions (5 minutes each, 30 minutes apart) infused into the masseter muscle. During the second HS infusion, pain was modulated by PASAT, CPT, or control (HS alone). HS-evoked pain intensity was scored on a 0 to 10 numeric rating scale (NRS). Heart rate variability (HRV) and hemodynamic measures were recorded noninvasively (Task Force Monitor). Data were analyzed using repeated measurements ANOVAs and Spearman correlation analysis., Results: HS-evoked pain was significantly and similarly reduced by both PASAT (30.8 ± 27.6%; P < .001) and CPT (35.8 ± 26.6%; P < .001) compared with the control session (9.0 ± 30.5%; P > .05). PASAT and CPT increased the heart rate compared with control (P <.001). CPT reduced measures of vagal activity: Root mean square successive difference, high-frequency (HF) power, and coefficient of HF component variance compared with an internal control, ie, the first HS infusion (P < .05), while PASAT did not alter any of these HRV measures (P > .05)., Conclusion: CPT and PASAT reduced HS-evoked masseter muscle pain and altered the autonomic response. The increase in heart rate following CPT and PASAT may be caused by different mechanisms. CPT reduced measures of efferent cardiac vagal (parasympathetic) activity, while the PASAT-induced increase in heart rate, but unchanged HRV, may suggest neurohumoral activation.

In a recent study we found that 4 weeks of human experimental forearm immobilization induced hypersensitivity to mechanical and cold stimuli and a higher skin temperature on the immobilized hand. Identical findings are reported in immobilization studies in rats where increased substance P signaling is suggested to play a central role. Capsaicin releases substance P from axon collaterals in the periphery initiating vasodilatation and plasma extravasation. The effect of immobilization on capsaicin-induced responses is, however, not known. Therefore, the present study examined the effect of experimental forearm immobilization on capsaicin-induced pain and flare responses in healthy subjects. Twenty-seven human volunteers were exposed to 4 weeks of scaphoid cast immobilization of the left forearm. Before and after immobilization, skin temperature and blood flow were measured at the thumbs of both hands during 5 min of rest. Subjects then received topical capsaicin (5%) randomly on the dorsum of the right and left hands. Time to sensory detection of capsaicin and pain onset was significantly increased on the immobilized left hand. Immobilization significantly reduced capsaicin-evoked pain, neurogenic flare area, and skin blood flow (perfusion units), and the reduced capsaicin-evoked pain was significantly correlated to an increase in peripheral skin temperature but not to skin blood flow. The correlation between reduced capsaicin-evoked pain and increased skin temperature suggests an increased substance P release while the delayed onset and diminished magnitude of capsaicin-induced pain may be due to reduced penetration of capsaicin into the epidermis.

Thoracic aortic dissection is a life-threatening emergency that must be met and surmounted immediately to increase survival. In this case, telemedicine involving ECG and GSM-based communication between the patient in the ambulance and the centre doctor was used to obtain remote pre-hospital suspicion of aorta dissection. Thus, the ambulance was re-routed directly to a specialized unit where the diagnosis was confirmed and immediate and successful surgical treatment was performed. Telemedicine allowing direct communication between the patient and the doctor is recommended.

Mortality in untreated pulmonary embolism is high and short-term outcome depends on a timely diagnosis. In this case telemedicine involving 12-lead ECG and GSM-based communication between the patient in the ambulance and the telemedical staff resulted in remote pre-hospital suspicion of acute pulmonary embolism. The ambulance was referred directly to the nearest department of cardiology where acute CT and echocardiography confirmed the diagnosis. Acute trombolysis was successful. Telemedicine may be beneficial in other medical emergencies than acute myocardial infarction.

The main aim was to investigate if acutely stressed subjects have abnormal heart rate variability responses to acute pain. Efferent cardiac autonomic activity was assessed by analyzing RR interval variation in 26 male volunteers. Heart rate variability was measured as mean and standard deviation of normal RR intervals (mean RR, SDNN) and by power spectral analysis where high frequency (HF) and low frequency (LF) power were used as indexes of vagal function and of sympatho-vagal interaction, respectively. Coefficient of component variance in the LF and HF bands (CCV-LF, CCV-HF) was estimated to adjust for possible influences of different mean RR levels on power amplitude. Subjects received painful and non-painful sural nerve stimulations during rest, during attention to pain, and during mental stress. Our results show that pain significantly decreased mean RR and increased LF power and CCV-LF during rest and during attention to pain. SDNN, HF power, and total power were not affected by pain. During mental stress, pain significantly decreased mean RR but failed to affect other heart rate variability parameters. We conclude that acute pain induced efferent cardiac sympathetic activation during rest and during attention to pain as LF power and CCV-LF increased without alterations of pure vagal heart rate variability measures. During mental stress, pain inhibited mean RR without changing heart rate variability measures suggesting that pain does not increase efferent cardiac sympathetic activity during mental stress. Pain induced decrease of mean RR during mental stress may be caused by the release of catecholamines into the systemic circulation.