Search Results (1,181)

Threat activation or deactivation in the brain–body is associated with learned nocebo or placebo somatic effects induced by fake invasive medical–surgical procedures. Some functional somatic disorders (FSDs) originate as acute nocebo somatic effects and can become 30–50% of chronic somatic presentations to primary care physicians. Patients with FSD overutilize medical–surgical services, despite the lack of identified pathophysiology, and are at risk for morbidity from unintentional iatrogenic injury. The Conditioned Response Model (CRM) of learning postulates three innate mechanisms, modulated by trait hypnotizability, which drive placebo and nocebo somatic effects and FSD. The High Risk Model of Threat Perception (HRMTP) postulates 10 psychosocial risk factors that modulate threat perception, driving placebo and nocebo somatic effectsandbiologically embedded FSD. Psychosocial factors and the trait of high and low hypnotizability modulate threat and are postulated to reduce heart rate variability(HRV), inducing autonomic nervous system(ANS)dysregulation. Reduced HRV was found in a large (N = 6,891) sample of patients with FSD. A total of 50% of patients with FSD with chronic pain (n = 224) without identified pathophysiology had a Paradoxical Increase in hand Temperature (PTI) during experimental threat induction. The HRMTP predicts that PTI associated with ANS dysregulation is associated with the risk factor Adverse Childhood Experiences (ACEs). This ACE prediction was independently confirmed. Learning predicts that threat activation by unconscious neutral stimuli (CS) can amplify nocebo and FSD and can negate placebo effects in clinician–patient relationships. Identifying psychosocial risk factors that modulate threat perception enables the diagnosis of FSD by inclusion and not simply by excluding pathophysiology. Full article

Background/Objectives: Heart rate variability (HRV) is a reliable, non-invasive marker of autonomic nervous system function and is often impaired in individuals with metabolic syndrome (MetS). Physical exercise has emerged as an effective strategy to improve autonomic modulation; however, the comparative effects of different training modalities on HRV in individuals with MetS remain unclear. This systematic review and meta-analysis aimed to evaluate the impact of various exercise interventions on HRV and to identify which training types yield the most significant improvements. Methods: A systematic search was conducted in PubMed and Scopus up to April 2025. Eligible studies (n = 16) included adults with obesity and MetS (n = 752) who underwent structured exercise interventions with HRV assessments pre- and post-intervention. Standardized mean differences were calculated using random effects models. Subgroup analyses were performed based on training modality (endurance training [ET], resistance training [RT], high-intensity interval training [HIIT], and concurrent training [CT]). Results: Sixteen studies of moderate to high quality were included, with eleven studies eligible for meta-analysis. ET and HIIT significantly improved time-domain indices (Root mean square of differences of successive R-R intervals —rMSSD—, Standard deviation of the R-R interval series —SDNN—) and frequency-domain parameters (high-frequency —HF—), suggesting enhanced parasympathetic activity. RT showed inconsistent effects, while CT improved long-term HF and total power (TP). Non-linear indices were the least reported due to insufficient data. Conclusions: Physical exercise—particularly ET and HIIT—appears to enhance cardiac autonomic modulation in individuals with obesity and MetS. These findings support incorporating targeted training strategies into clinical practice to optimize cardiovascular health in these populations. Full article

Sexual behavior is a complex process in which the brain plays an active role. In the male rat, stimuli from the female are perceived through sensory receptors related to olfaction, hearing, vision, and the perigenital area, priming the individual for a sexual response. This process culminates with ejaculation and the deposition of semen into the uterine tract with the aim of achieving fertilization. The brain plays a fundamental role in both generating motivation and executing male sexual behavior. Meanwhile, the spinal cord, through the autonomic nervous system and the pelvic ganglion, transmits information to the reproductive organs, including the testes. Currently, there is extensive evidence demonstrating the involvement of various brain structures in the regulation of sexual behavior, as well as specific regions of the spinal cord involved in the control of ejaculation. For instance, the medial preoptic area (MPOA) has been shown to regulate the secretion of pituitary hormones, which in turn modulate the function of reproductive organs. Among these, testosterone production is particularly notable, as this hormone not only directly affects reproductive organs but also exerts a modulatory role on brain nuclei responsible for sexual behavior. Although there is a reciprocal regulation between the nervous and endocrine systems, it is important to note that the execution of sexual behavior also impacts peripheral structures, such as the major pelvic ganglion (MPG) and the testis, preparing the organism for reproduction. The purpose of this mini-review is to provide an overview of the main brain nuclei involved in the regulation of sexual behavior, as well as the spinal cord regions implicated in reproduction. Finally, we discuss how these structures may alter their function in the context of neurodegenerative diseases, aiming to introduce readers to this field of study. Full article

Spinal cord injury (SCI) results in significant motor, sensory, and autonomic dysfunction. The pathophysiology of SCI develops during the primary and secondary phases. Inflammation contributes to the secondary phase through the non-specific activation of the innate immune response. Glial scar formation (gliosis), a reactive cellular mechanism facilitated by astrocytes, also occurs during this phase. Synthetic steroids such as tibolone (Tib) have been proposed as a treatment for SCI since they exert neuroprotective effects in various models of central nervous system (CNS) injury. We studied the effect of Tib on locomotor functional recovery and the regulation of neuroinflammation and gliosis in an SCI model. We performed an SCI at the thoracic vertebrae nine in male Sprague Dawley rats. The animals received daily doses of Tib (1 or 2.5 mg per kg of body weight) administered orally. We quantified pro- and anti-inflammatory cytokine levels at the injury site and determined motor recovery using the Basso, Beattie, and Bresnahan (BBB) scale. Finally, we investigated the effect of Tib on the expression of glial fibrillary acidic protein (GFAP) and ionized calcium-binding adaptor molecule 1 (Iba-1), two markers of gliosis, using an immunohistochemistry assay. Our findings showed that Tib regulated pro- and anti-inflammatory cytokine levels at 3 h and 3, 7, and 14 days post-SCI. Furthermore, Tib administered orally for 15 days reduced gliosis markers and favored tissue preservation and motor function recovery after SCI. Full article

Background: Persistent fatigue is among the most commonly reported symptoms in patients suffering from post-acute sequelae of SARS-CoV-2 infection (long COVID). Autonomic dysfunction, measurable via heart rate variability, has been implicated as a contributing factor. Osteopathic manipulative treatment is a manual therapeutic approach that targets autonomic balance and may offer a novel intervention for long COVID-related fatigue. Methods: In this single-blind, randomized controlled trial, 42 participants (mean age 51 ± 11 years; fatigue severity score: 31 ± 5 points) with long COVID and persistent fatigue ≥12 weeks post-infection were allocated to either a 45 min standardized osteopathic treatment (n = 21) or a sham-treatment group (n = 21). Heart rate variability was assessed using a 10 min resting electrocardiogram before intervention, immediately after, and again 48 h later. The analysis of heart rate variability encompassed time-domain indices, including the root mean square of successive differences, the standard deviation of normal-to-normal intervals, mean heart rate, and mean RR interval. Additionally, frequency-domain measures such as low-frequency, high-frequency, total power, and the LF/HF ratio were considered. Results: The osteopathy group showed a statistically significant increase in root mean square of successive differences post-treatment (p < 0.01), accompanied by a decrease in the stress index (p < 0.05) and an increase in the mean of the standard deviations of RR intervals (p < 0.05). Significant between-group differences were observed for mean heart rate and mean of RR intervals (p < 0.05). Frequency-domain measures also improved significantly from baseline in the intervention group. Outlier patterns suggest potential subgroup effects, possibly due to underlying dysautonomia. Conclusions: A single session of osteopathic treatment significantly enhanced short-term heart rate variability in long COVID patients with fatigue. These findings highlight the potential role of manual autonomic modulation as a supportive therapy in long COVID management. Further research is needed to assess the long-term effects and optimal treatment frequency of osteopathic manipulative treatment in this population. Full article

Background: Parkinson’s disease (PD) is a progressive neurodegenerative disorder characterized by both motor and non-motor symptoms, including autonomic dysfunction. Structural alterations in the vagus nerve (VN) may contribute to PD pathophysiology, though existing data remain inconsistent. Objective: This study aimed to evaluate morphological changes in the VN using high-resolution ultrasound (USVN) and to investigate associations with autonomic symptoms, heart rate variability (HRV), and clinical characteristics in PD patients. Methods: A cross-sectional study was conducted involving 60 PD patients and 60 age- and sex-matched healthy controls. USVN was performed to assess VN cross-sectional area (CSA), echogenicity, and homogeneity bilaterally. Autonomic symptoms were measured using the Composite Autonomic Symptom Scale 31 (COMPASS-31). HRV parameters—SDNN, RMSSD, and pNN50—were obtained via 24 h Holter monitoring. Additional clinical data included Unified Parkinson’s Disease Rating Scale (UPDRS) scores, transcranial sonography findings, and third ventricle width. Results: PD patients showed significantly reduced VN CSA compared to controls (right: 1.90 ± 0.19 mm² vs. 2.07 ± 0.18 mm²; left: 1.74 ± 0.21 mm² vs. 1.87 ± 0.22 mm²; p < 0.001 and p < 0.02). Altered echogenicity and decreased homogeneity were also observed. Right VN CSA correlated with body weight, third ventricle size, and COMPASS-31 scores. Left VN CSA was associated with body size parameters and negatively correlated with RMSSD (p = 0.025, r = −0.21), indicating reduced vagal tone. Conclusions: USVN detects structural VN changes in PD, correlating with autonomic dysfunction. These findings support its potential as a non-invasive biomarker for early autonomic involvement in PD. Full article

The heart–brain axis (HBA) is a dynamic system of reciprocal communication between the cardiovascular and central nervous system, incorporating neural, immunologic, molecular and hormonal pathways. The central autonomic network is described as a key regulator of cardiovascular activity and autonomic dysfunction as an important mechanism underlying various neurologic and cardiac disorders. Heart rate variability (HRV) is identified as the key biomarker of the axis reflecting autonomic nervous system balance. Increased understanding of its molecular mechanisms has led to the proposal of new therapeutic strategies focused on modulating heart–brain communication including β-blockers, vagus nerve stimulation, neurotrophin modulation, and nanoparticle-based approaches. The integration of wearables and artificial intelligence (AI) has allowed for real-time monitoring and innovative diagnostic and prognostic applications. The present narrative review summarizes current knowledge on the mechanisms comprising the heart–brain axis, their implication in neurologic and cardiac disorders, and their potential for developing novel therapies. It also highlights how advancements in wearable technology and AI systems are being integrated into clinical practice and transforming the landscape. Full article

In this preliminary study, the thermoregulatory response in individuals diagnosed with Parkinson’s disease was investigated by infrared thermography. Parkinson’s disease is a complex neurodegenerative disorder primarily known for motor impairments, significantly reducing the quality of life of affected people. However, in most cases, such disease is accompanied or preceded by non-motor symptoms, including autonomic dysfunction. As in the case of neurovegetative dysautonomia, this dysfunction involves a malfunction of the autonomic nervous system, which also plays a key role in thermoregulation. In general, such conditions are not always easy to detect; a valid method could be represented by the vasomotor response of the skin to cold stimuli. In this context, infrared thermography can provide insights into the thermoregulatory patterns associated with autonomic dysfunction, representing a valuable tool for non-invasive assessment of Parkinson’s research. Early biomarkers of the disease can be obtained through changes in skin temperature, allowing for timely intervention and management. The study was conducted on a cohort of 16 subjects (8 patients with Parkinson’s disease and 8 healthy controls), who were monitored with infrared images captured from their hands, following a specific protocol established by a preliminary analysis. Experimental results revealed that thermography can detect focal points and regions exhibiting either hyper- or hypothermia across the skin surface and muscular regions. This capability allows for extracting and categorizing precise medical data, which could inform future research aimed at identifying early markers of the disease. However, as this is a preliminary observational study, no diagnostic claims are made, and further investigations on larger cohorts with controlled comorbidities are needed. Full article

The renin-angiotensin system (RAS) has evolved from being considered solely a peripheral endocrine system for cardiovascular control to being recognized as a complex molecular network with important functions in the central nervous system (CNS) and peripheral nervous system (PNS). Here we examine the organization, mechanisms of action, and clinical implications of cerebral RAS in physiological conditions and in various neurological pathologies. The cerebral RAS operates autonomously, synthesizing its main components locally due to restrictions imposed by the blood–brain barrier. The key elements of the system are (pro)renin; (pro)renin receptor (PRR); angiotensinogen; angiotensin-converting enzyme types 1 and 2 (ACE1 and ACE2); angiotensin I (AngI), angiotensin II (AngII), angiotensin III (AngIII), angiotensin IV (AngIV), angiotensin A (AngA), and angiotensin 1-7 (Ang(1-7)) peptides; RAS-regulating aminopeptidases; and AT1 (AT1R), AT2 (AT2R), AT4 (AT4R/IRAP), and Mas (MasR) receptors. More recently, alamandine and its MrgD receptor have been included. They are distributed in specific brain regions such as the hypothalamus, hippocampus, cerebral cortex, and brainstem. The system is organized into two opposing axes: the classical axis (renin/ACE1/AngII/AT1R) with vasoconstrictive, proinflammatory, and prooxidative effects, and the alternative axes AngII/AT2R, AngIV/AT4R/IRAP, ACE2/Ang(1-7)/MasR and alamandine/MrgD receptor, with vasodilatory, anti-inflammatory, and neuroprotective properties. This functional duality allows us to understand its role in neurological physiopathology. RAS dysregulation is implicated in multiple neurodegenerative diseases, including Alzheimer’s disease (AD), Parkinson’s disease (PD), and neuropsychiatric disorders such as depression and anxiety. In brain aging, an imbalance toward hyperactivation of the renin/ACE1/AngII/AT1R axis is observed, contributing to cognitive impairment and neuroinflammation. Epidemiological studies and clinical trials have shown that pharmacological modulation of the RAS using ACE inhibitors (ACEIs) and AT1R antagonists (ARA-II) not only controls blood pressure but also offers neuroprotective benefits, reducing the incidence of cognitive decline and dementia. These effects are attributed to direct mechanisms on the CNS, including reduction of oxidative stress, decreased neuroinflammation, and improved cerebral blood flow. Full article

Background/Objectives. Heart rate variability (HRV) is the variability in the beat-by-beat heart period. Primary focal hyperhidrosis (PFHH) is a disease characterized by excessive sweat production, strongly affecting social life. Several authors define this condition as a dysautonomic disorder, mainly driven by exaggerated sympathetic activity. The aim of the study was to demonstrate a possible cardiac involvement in the disease. Other outcomes were the occurrence of dysautonomic disorders after surgery and its possible correlation with baseline characteristics. Methods. This observational, controlled trial enrolled patients with a confirmed clinical diagnosis of severe PFHH candidates to thoracoscopic sympathetic chain clamping. Before and after surgery, ECG was obtained using KardiaMobile 6L (AliveCor^®, Mountain View, CA, USA) device with a five-minute recording and HRV was analyzed using Kubios HRV Premium (Kubios©) software. Results. 111 patients were compared to 222 healthy control subjects. No differences were seen in HRV analysis between the two groups at baseline (time-domain p > 0.05, frequency-domain p > 0.05, autonomic indexes p > 0.05). When comparing autonomic function indexes in patients before and after the surgical procedure, no differences were seen in frequency-domain HRV analysis, but a blunted increase in SNS index (0.2 vs. 1.38, p 0.02). No development of systemic dysautonomic disorders nor significant compensatory hyperhidrosis were seen after the surgery. Conclusions. This study shows that PFHH is a peripheral autonomic nervous system derangement, rather than central. Sympathetic chain clamping resulted safe and effective in improving patients’ conditions, with no risks of dysautonomic disorders. Full article

There is growing evidence regarding non-pharmacological therapies such as music as a supportive approach for the treatment of various clinical conditions in humans. Physiological and neurobiological research suggests that music exposure is related to endorphin, endocannabinoid and dopamine release, favourable effects on autonomic nervous system functioning and is associated with decreased pain perception and reduced stress response. Further evidence in humans demonstrates a beneficial role of music application during the perioperative period by improving various outcome measures, such as the perioperative stress and anxiety levels, the sedation or general anaesthetic requirements, the pain levels, the analgesic requirements and other parameters related to patient prognosis, without reported side effects. Accordingly, such interventions have been considered as a method of environmental enrichment for animal welfare enhancement, by masking potentially disturbing background noises and by ameliorating anxiety or aggressive behaviours in different stressful settings in dogs and cats. Furthermore, research has been lately extended to the potential music’s effect in these species during the perioperative period, considered a stressful setting, as well. This review presents the existing evidence of music application focusing on the perioperative period of dogs and cats, as part of a multimodal approach, to improve their surgical outcome and welfare. Full article

Spinal cord injury (SCI) remains a devastating neurological condition characterized by loss of sensory, motor and autonomic function. Despite decades of research, no FDA-approved regenerative therapies currently exist to restore lost function following SCI. Schwann cells (SCs) support axon regeneration, remyelination, and neuroprotection after SCI, with their therapeutic potential validated in clinical trials demonstrating safe and feasible transplantation in humans. Although SC transplantation has shown promising results, challenges remain, including modest graft survival, limited host integration, and restricted migration that collectively contribute to constrain efficacy. To address these limitations, biomaterial scaffolds have been explored as synergistic platforms to enhance SC delivery and function. When combined with natural or synthetic biomaterials such as hydrogels, nanofiber scaffolds, or ECM-mimetic matrices, SCs demonstrate improved survival, retention, spatial distribution, and regenerative activity. The intrinsic regenerative properties of SCs, first demonstrated in models of peripheral nerve injury, make them particularly well-suited for neural repair of the central nervous system (CNS) compared to other cell types and their effectiveness can be enhanced synergistically when combined with biomaterials. These constructs not only provide structural support but also modulate the lesion microenvironment, enhance axon growth and improve SC integration with host tissue. Combinatorial approaches incorporating biomaterials with SCs are emerging as next-generation strategies to optimize repair for clinical translation. This review focuses on current progress in SC-based therapies combined with biomaterials, highlighting key preclinical advances, clinical translation efforts, and the path forward toward effective regenerative interventions for SCI. Full article

Longevity and healthy aging result from the complex interaction of genetic, epigenetic, microbial, behavioral, and environmental factors. The central nervous system—particularly the cerebral cortex—and the autonomic nervous system (ANS) play key roles in integrating external and internal signals, shaping energy metabolism, immune tone, and emotional regulation. This narrative review examines how the brain–ANS axis interacts with epigenetic regulation, telomere dynamics, the gut microbiome, and the exposome to influence biological aging and resilience. Relevant literature published between 2010 and 2025 was selected through comprehensive database searches (PubMed, Scopus, Google Scholar), with a focus on studies addressing the multisystemic determinants of aging. Emphasis is placed on lifestyle-related exposures, such as diet, physical activity, psychosocial support, and environmental quality, that modulate systemic physiology through neurovisceral pathways. Drawing on empirical findings from classical Blue Zones and recent observational research in the Cilento region of southern Italy, this review highlights how context-specific factors—such as clean air, mineral-rich water, Mediterranean dietary patterns, and strong social cohesion—may foster bioelectric, metabolic, and neuroimmune homeostasis. By integrating data from neuroscience, systems biology, and environmental epidemiology, the review proposes a comprehensive model for understanding healthy longevity and supports the development of personalized, context-sensitive strategies in geroscience and preventive medicine. Full article

Background: Chronic musculoskeletal pain (CMP) is a multidimensional condition involving both peripheral and central mechanisms, with increasing evidence supporting an interplay between subjective pain perception and autonomic nervous system (ANS) function. However, few studies have explored whether a single non-invasive intervention can concurrently modulate both domains. Objectives: To evaluate the short-term effects of a single session of Pulsed Electromagnetic Field (PEMF) therapy—administered via the PAP Ion Magnetic Induction (PAPIMI™) device—on subjective pain intensity and heart rate variability (HRV) parameters in individuals with CMP. The relationship between perceived pain relief and physiological autonomic adaptations was also explored. Methods: Thirty adults with CMP underwent a single PAPIMI™ session. Subjective pain intensity was measured using the Numeric Pain Rating Scale (NPRS), while autonomic function was assessed via HRV. Pre- to post-intervention changes were analyzed using the Wilcoxon Signed-Rank test, while Spearman’s correlation was computed to assess associations between post-intervention changes in subjective perceived pain and HRV parameters. Results: A significant reduction in NPRS scores (p < 0.001) was found after PAPIMI intervention. Also, a significant increase in specific parasympathetic-related HRV indices, namely, RMSSD (p = 0.015) and HF power (p = 0.029), was observed. No significant correlations were found between post-intervention changes in pain perception and HRV metrics. Conclusions: A single PAPIMI session induced both analgesic effects and improvements in autonomic balance in individuals with CMP. These findings underscore the potential of PAPIMI as a non-pharmacological approach for rapid pain modulation and systemic rebalancing. Full article

Thirst is usually characterized as an unpleasant sensation provoking drinking of water. The purpose of the present review is to draw attention to the importance of thirst in overall regulation of body fluid homeostasis in health and pathology. Intensity of thirst is determined by signals generated in multiple groups of osmosensitive neurons engaged in dipsogenic and antidipsogenic activities, which are located in the brain cortex, the insula, the amygdala, the median preoptic area, the hypothalamic nuclei and the organum vasculosum laminae terminalis. Water ingestion is also influenced by signals generated in the cardiovascular system, the gastrointestinal system, the pancreas, the liver and the kidney and by changes of body temperature. Regulation of thirst engages the autonomic nervous system and several neuroactive factors synthetized in the brain and the peripheral organs. Among them are components of the renin–angiotensin system, vasopressin, atrial natriuretic peptide, cholecystokinin, ghrelin, gaseous transmitters, cytokines and prostaglandins. Experimental studies provide evidence that elevation of fluid osmolality, which is the most frequent cause of thirst, influences function of the voltage-gated sodium channel and calcium-dependent kinase II subunit alpha. Regulation of thirst may be inappropriate in old age and under some pathological conditions including infections, heart failure, diabetes insipidus, diabetes mellitus, and psychogenic disorders. The molecular background of the abnormal regulation of thirst in the clinical disorders is not yet sufficiently recognized and requires further examination. Full article