Search Results (37)

Objective: This study developed the Uncertain Drop Stress Test (UDST), an uncertain stress induction paradigm based on the high survival-relevant threat of fear of falling, wherein neither the occurrence nor the timing of the fall is predictable. The aim was to compare its stress induction efficacy and neural oscillatory changes with those of the Socially Evaluated Cold Pressor Test (SECPT), a certain stress paradigm, and to examine gender differences. Methods: Forty-eight participants (24 males; 24 females) were recruited. Psychological indicators (subjective stress, negative affect, and state anxiety) and physiological indicators (heart rate, heart rate variability, galvanic skin response, and salivary cortisol) were measured before and after stress to compare induction efficacy. Resting-state EEG was collected for frequency domain analysis to explore neural oscillatory changes. Results: UDST induced more pronounced psychophysiological changes. Notably, only UDST significantly decreased heart rate variability and increased galvanic skin response. UDST triggered an “exogenous vigilance mode” characterized by enhanced high-frequency (Beta/Gamma) activity, whereas SECPT elicited an “interoceptive focusing mode” characterized by suppressed low-frequency (Theta/Alpha) activity. Females exhibited higher heart rate and Beta activity than males under both stress conditions. Conclusions: UDST elicits stronger psychophysiological responses and distinct neural oscillatory patterns, with females showing greater stress reactivity. Full article

Introduction: Migraine is featured by altered nociceptive processing and the presence of cognitive impairments. No study has previously investigated the influence of neurocognitive performance and executive functions in descending pain processing in this population. Aim: To assess the influence of neurocognitive processes and executive functions in conditioned pain modulation (CPM) activation in women with migraine. Methods: A cross-sectional case–control study including 140 women with migraine (50% chronic) and 70 control women was conducted. Clinical migraine features, neurocognitive processes (e.g., attention), and executive functions (memory, mental inhibition, speed of processing) were evaluated. Pressure pain thresholds (PPTs) were bilaterally assessed at the temporalis muscle, lateral epicondyle, and tibialis anterior muscle. Heat (HPT) and cold (CPT) pain thresholds were assessed at the frontalis (trigeminal area) muscle. Thus, CPM was evaluated with the cold pressor test paradigm by analyzing changes in mechanical/thermal stimuli after a conditioned stimulus. Results: Significant group*time interactions not associated with neurocognitive process/executive function, educational level, and employment status were found for PPTs at the temporalis muscle (Wilk’s λ = 0.588, F[2,199] = 69.756, p < 0.001, n²p = 0.412, 1 − β = 0.999), lateral epicondyle (Wilk’s λ = 0.674, F[2,200] = 48.331, p < 0.001, n²p = 0.326, 1 − β = 0.999), and tibialis anterior (Wilk’s λ = 0.751, F[2,200] = 33.110, p < 0.001, n²p= 0.249, 1 − β = 0.999): PPTs were higher after the conditioned stimulus in all points in control women (increases ranging from 11% to 17%), whereas PPTs were lower after the conditioned stimulus in women with migraine (decrease from −7.5% to −0.1%) when compared with PPTs at baseline. Changes in HPT and CPT were small and not significant, ranging from 0.1% to 0.5%. Conclusion: This study revealed that women with episodic or chronic migraine showed CPM deficits particularly against mechanical stimuli when compared with pain-free women. Neurocognitive (e.g., attention) processes or executive functions (e.g., working memory, mental inhibition) did not modulate CPM activity in women with migraine. Full article

High levels of stress and individual differences in acute stress responses are important predictors of chronic illness. This study examined the effects of stress and Alcohol Use Disorder (AUD) on heart rate variability (HRV) using the Yale Pain Stress Test (YPST), adapted from the well-established Cold Pressor Test (CPT). The YPST characterized three key (time periods) phases of the cardiovascular stress response to repeated trials of a pain-stress versus no pain-stress control condition: pre-stress baseline, acute reactivity, and recovery, using HRV as a physiological marker. Participants included 24 individuals who engaged in social drinking and 21 participants with AUD, all recruited from the Greater New Haven area. They were screened for psychiatric or medical conditions and other substance use disorders using DSM-5 criteria. Results showed significant main effects of stress condition and time across HRV metrics. While no significant three-way interaction among time period, condition, and drinking group was observed, there were significant condition × time period effects and group × condition effects. Participants with AUD exhibited lower high-frequency (HF) and low-frequency (LF) HRV during stress exposure compared to the recovery phase. They also showed a less dynamic LF/HF ratio during stress relative to social drinking controls, suggesting greater sympathetic dominance. In contrast, participants who engaged in social drinking displayed autonomic flexibility across time periods. Findings suggest that individuals with AUD experience blunted autonomic reactivity and reduced HRV recovery following stress, highlighting diminished physiological flexibility potentially indicating risk for long-term stress-related chronic diseases. The results underscore the importance of evaluating autonomic function in clinical care and recovery planning for individuals with AUD. Full article

Acute stress impairs executive functions, and these higher-order cognitive processes are often positively associated with intelligence. Even though intelligence is generally stable over time, performance in an intelligence test can be influenced by a variety of factors, including psychological processes like motivation or attention. For instance, test anxiety has been shown to correlate with individual differences in intelligence test performance, and theoretical accounts exist for causality in both directions. However, the potential impact of acute stress before or during an intelligence test remains elusive. Here, in a research context, we investigated the effects of test anxiety and acute stress as well as their interaction on performance in the short version of the Intelligence Structure Test 2000 in its German version (I-S-T 2000 R). Forty male participants completed two sessions scheduled 28 days apart, with the order counterbalanced across participants. In both sessions, participants underwent either the socially evaluated cold-pressor test (SECPT) or a non-stressful control procedure, followed by administration of I-S-T 2000 R (parallelized versions on both days). The SECPT is a widely used laboratory paradigm that elicits a stress response through the combination of psychosocial and physical components. Trait test anxiety scores were obtained via the German Test Anxiety Inventory (TAI-G). Stress induction was successful as indicated by physiological and subjective markers, including salivary cortisol concentrations. We applied linear mixed models to investigate the effects of acute stress (elicited by our stress manipulation) and test anxiety on the intelligence quotient (IQ). The analysis revealed that neither factor had a significant effect, nor was there a significant interaction between them. Consistent with these findings, Bayesian analyses provided evidence supporting the absence of these effects. Notably, IQ scores increased significantly from the first to the second testing day. These results suggest that neither test anxiety nor stress is significantly impacting intelligence test performance. However, improvements due to repeated testing call for caution, both in scientific and clinical settings. Full article

Objectives: Chronic pain corresponds to hypersensitivity to painful stimuli; however, its relation to acute pain sensitivity in children is poorly understood. We explored this relationship by comparing acute and chronic pain measures, along with related factors, in children with chronic pain syndromes versus controls, before and after therapeutic intervention. Methods: This prospective controlled cohort study involved 57 children with chronic pain undergoing intensive interdisciplinary pain treatment in a hospital-based pain rehabilitation program and 50 controls. Participants, aged 7–18, were tested using a cold pressor task (CPT) at admission, discharge, and first follow-up visit. Data on sleep, anxiety, psychological distress, functional impairment, and pain were collected. Results: Significant differences were found between control and treatment groups in average pain threshold (p < 0.001), pain tolerance (p = 0.035), sleep visual analog scale (VAS) (p < 0.001), functional disability inventory (p < 0.001), patient reported outcomes information system anxiety assessment tool (p < 0.001), general anxiety disorder 7-item scale (p < 0.001), pain VAS (p < 0.001) and total brief symptom inventory (BSI) (p < 0.001) scores at admission with children with chronic pain scoring worse on all measures save the pain VAS during the CPT. After treatment and at follow-up, function and mental health measures improved but not acute pain threshold. Conclusions: At treatment completion, function and mental health significantly improved but acute pain threshold and sleep quality were unchanged. These findings suggest that while chronic pain treatment improves overall function and mental health, acute pain thresholds may not be a suitable indicator for evaluating the efficacy of interventions. Full article

Background: The increasing use of virtual reality (VR) has extended into medical applications, including pain management through immersive mechanisms. This study aimed to evaluate the effectiveness of the Clone Hero for reducing pain intensity, threshold and tolerance. Methods: A randomized crossover trial compared three conditions during a cold pressor test in 25 healthy volunteers over 35 years: playing Clone Hero (interactive), watching Clone Hero (control), or no intervention (placebo). Outcome measures included usability and acceptability (qualitative questionnaire), pain intensity (VAS), pain threshold, pain tolerance, physical activity (IPAQ), and adverse effects. Results: Twenty-five participants completed the study. Overall satisfaction was high, with 92% reporting a positive experience. The Clone Hero group showed significantly lower pain intensity scores (4.9 ± 0.49) than the placebo (5.6 ± 0.48; p = 0.037) and control groups (6.1 ± 0.42; p = 0.004). Pain threshold was higher in the Clone Hero group (74.45 ± 20.7 s) compared to the placebo (62.91 ± 18.58; p < 0.001) and control (43 ± 14.77; p = 0.001). Pain tolerance was also greater (127.6 ± 9.46 s) versus the placebo (p = 0.021) and control (p = 0.001). No serious adverse effects were reported. Conclusions: Interactive pain management interventions demonstrated high levels of acceptability and user satisfaction, and may enhance pain modulation more effectively than passive or control. Full article

Background: The International Association for the Study of Pain (IASP) conceptualizes pain as a subjective experience, influenced by biopsychosocial factors, strongly related to the person’s environment and previous experience. It is necessary to understand painful experiences from birth and their influence on the self-perception of pain later in life. In addition, training competent health professionals to identify and treat pain becomes a priority. The main objective of the protocol is to describe the situations that influence pain perception. These influences are conceived from birth to adulthood, taking into account the gender perspective. Methods: This is a two-year exploratory mixed-methods educational intervention design, incorporating cross-sectional assessments at baseline. The research will be carried out in the academic community, including nursing students from two universities. The following will be carried out: (1) practical seminars (groups of 20–25) to increase future healthcare professionals’ awareness of pain-inducing procedures and critical thinking; (2) a peer-mentoring session, led by senior students, addressing pain research, its clinical impact, and strategies for improved pain management through theoretical and practical components; (3) supervised sessions, where students will learn and perform vital sign measurements (HR, SpO₂), algometry, and the Cold Pressor Test (CPT) to assess pain perception, threshold, and tolerance, practicing in pairs; (4) a gender-specific questionnaire to evaluate students’ perceptions of pain, fostering reflection on gender differences in pain experiences. Discussion: The aim is to enhance knowledge about pain in future health professionals to increase their skills in the approach to pain. Conclusions: This study aims to promote formal academic contact between higher education students, promoting comprehensive care in the management of pain at different stages of life. Full article

A wearable closed-loop transcutaneous electrical nerve stimulation (TENS) platform has been developed to address the limitations of conventional open-loop neuromodulation systems. Unlike existing systems such as CLoSES—which targets intracranial stimulation—and electromyography-triggered functional electrical stimulation (EMG-FES) platforms primarily used for motor rehabilitation, the proposed device uniquely integrates low-latency surface electromyography (sEMG)-driven control with six-channel current stimulation in a fully wearable, non-invasive format aimed at ambulatory pain modulation. The system combines real-time sEMG acquisition, adaptive signal processing, a programmable multi-channel stimulation engine, and a high-voltage, boost-regulated power supply within a compact, battery-powered architecture. Bench-top evaluations demonstrate rapid response to EMG events and stable biphasic output (±22 mA) across all channels with high electrical isolation. A human-subject protocol using the Cold Pressor Test (CPT), heart rate variability (HRV), and galvanic skin response (GSR) has been designed to evaluate analgesic efficacy. While institutional review board (IRB) approval is pending, the system establishes a robust foundation for future personalized, mobile neuromodulation therapies. Full article

Microalgae, a marine-derived natural ingredient, has emerged as a rich source of bioactive compounds with the potential to modulate gut–brain axis activities. The objective of this study was to investigate whether supplementation with a microalgae extract from Tetradesmus obliquus strain Mi175.B1.a (TOME) influences gut health and reduces stress and anxiety in healthy adults experiencing mild to moderate gastrointestinal (GI) distress. Methods: Fifty-six healthy adults (age: 31.9 ± 7.7 years; body weight: 71.8 ± 12.6 kg; BMI: 24.6 ± 2.8 kg/m²) were enrolled in a randomized, double-blind, placebo-controlled, parallel-arm clinical trial. Participants were randomly allocated to receive capsules containing either 250 mg/day of TOME or a placebo for four weeks. Primary outcomes included the assessment of GI symptoms using the Gastrointestinal Symptom Rating Scale (GSRS) and Bristol Stool Scale (BSS). Secondary outcomes focused on subjective evaluation of mood, stress, and anxiety, as well as blood pressure responses to sympathetic nervous system activation induced by the cold pressor test (CPT). In addition, stool, plasma, and saliva samples were collected to assess biomarkers associated with stress, sympathetic activation, intestinal permeability, and GI health. 16S rRNA sequencing was performed to analyze changes in gut microbial populations. Results: Daily supplementation for four weeks with TOME was safe and well tolerated in the study population. In addition, TOME significantly reduced GSRS global scores (p = 0.02), as well as constipation (p = 0.05) and indigestion (p = 0.03) subcomponent scores compared to Placebo. There was also a significant increase in Shannon’s index before FDR correction (p = 0.05; FDR = 0.12) and stool butyrate level was significantly lower in the TOME group than in Placebo after 4 weeks of supplementation (p = 0.039). Both groups showed a significant reduction in perceived stress scores, but the TOME intervention group also had reduced Negative Affect scores (p < 0.001). In addition, plasma chromogranin A, a stress biomarker, was significantly reduced after TOME intervention (p = 0.03). There were no negative effects on blood lipids or other parameters related to sympathetic activation or cardiovascular health. Conclusions: Overall, these results suggest that 4-week supplementation with T. obliquus strain Mi175.B1.a improves GI symptoms, potentially through effects on the gut microbiota, and may promote positive effects on mental health. Additional research should follow up on mental health outcomes in populations with increased stress and anxiety and investigate mechanisms underlying improvements in GI health. This trial was registered at clinicaltrials.gov as NCT06425094. Full article

Adrenergic receptors (AR) play a vital role in cardiovascular system regulation. The ADRB2 gene, encoding the β2-AR receptor, has genetic variability potentially impacting blood pressure (BP) regulation. Evidence for such associations has been inconsistent. This study investigates the relationship between two ADRB2 polymorphisms (rs1042713, Gly16Arg, and rs1042714, Glu27Gln) and BP changes during the cold pressor test (CPT) in young, healthy men, including combat athletes. The study included two groups: combat athletes and non-athlete students. BP (systolic, SBP; diastolic, DBP) was measured at rest and at pain tolerance during CPT. Genetic analysis was conducted for rs1042713 and rs1042714 polymorphisms. Athletes had higher SBP and DBP than students, with both values increasing during pain tolerance compared to rest. Differences in BP responses during CPT were genotype-dependent. Students with the Gly16Gly16 genotype had significantly higher SBP than Arg16 allele carriers, while this variation was not observed in athletes. Athletes with the Glu27 allele exhibited higher SBP than 27Gln homozygotes, unlike students. Gly16 and Glu27 alleles are linked to elevated stress-induced BP responses in young Polish men. However, BP regulation involves multiple genetic and environmental factors not explored in this study. Full article

Background/Objectives: For the rapid, objective characterization of the physiological stress response, there is currently no generally recognized standard. The stress measurement methods used in practice (e.g., for psychological measures of stress) are often subjective, or in the case of biological markers (e.g., cortisol, amylase), they usually require a blood test. For this reason, the use of heart rate variability (HRV) to characterize stress has recently come to the fore. HRV is the variability in the length of heartbeat intervals, which indicates the ability of the heart to respond to various physiological and environmental stimuli. However, the conventional HRV metrics are not corrected for heart rate dependence; hence, they fail to fully account for the complex physiology of stress and relaxation. In order to remedy this problem, here we introduce a novel HRV parameter, the normalized variability derived from an RMSSD “Master Curve”, and we compare it with the conventional metrics. Methods: In Study 1, the relaxation state was induced either by heart rate variability biofeedback training (N = 21) or by habitual relaxation (N = 21), while in Study 2 (N = 9), the Socially Evaluated Cold Pressor Test and the Socially Evaluated Stroop Test were used to induce stress in the subject. For a statistical evaluation of the data, the Kolmogorov–Smirnov test was used to compare the distributions of mean HR, log(RMSSD), log(SDNN), and normalized variability before, during, and after relaxation and stress. Results: The results of this study indicate that while log(RMSSD) and log(SDNN) did not change significantly, the normalized variability did undergo a significant change both in relaxation states and in stress states induced by the Socially Evaluated Cold Pressor Test. Conclusions: Overall, we suggest this novel type of normalized variability ought to be used as a sensitive stress indicator, and in general, for the characterization of the complex processes of the vegetative nervous system. Full article

In uncertain situations, individuals seek to maximize rewards while managing risks. Yet, the effects of acute stress and anxiety on decision-making in ambiguous and risky contexts are unclear. This study aims to contribute to the exploration of how acute stress influences sensitivity to immediate vs. delayed rewards, risk management strategies, and the role of anxiety in these processes. This study used the laboratory acute stress induction paradigm to analyze the direction of influence of acute stress on ambiguity decision-making and risky decision-making in males and then used moderating effect analysis to study the impact of anxiety on this process. The results show that a combination of the Socially Evaluated Cold Pressor Test and the Sing-a-Song Stress Test can successfully induce acute stress, which reduces both the proportion of the options selected that represent long-term rewards and risk-adjustment ability. Additionally, trait anxiety had a moderating effect on the influence of stress on ambiguity decision-making. Acute stress reduces focus on long-term rewards while increasing focus on short-term rewards, leading to impulsivity and impaired risk-adjustment. Additionally, to some extent, high trait anxiety scores predict better performance in making decisions under ambiguity during stress. Full article

Background/Objectives: Although increased nociceptive excitability and deficient endogenous pain modulation are considered key features of pronociception and central sensitization, their contribution to neuropathic pain (NP) characteristics in SCI is unclear. The aim of this study was to characterize tonic cold perception and endogenous pain modulation in individuals with and without SCI-NP, considering the stage and severity of SCI and, secondarily, NP phenotype. Methods: Temporal summation of pain (TSP) and neuropathic features were assessed using the numerical rating scale (NRS) and Douleur Neuropathique 4 screening questionnaire (DN4) during the tonic cold pressor test (CPT, 12 °C 60 s) applied to the dominant hand and foot. CPT-induced pronociception was assessed as change in algometer pressure pain thresholds (PPTs) measured at the V2, C6, and L4 dermatomes. Results: A total of 72 individuals were recruited (age-sex-matched noninjured, n = 24; SCI-NP, n = 24; SCI-noNP, n = 24 [AIS A: n = 12, AIS B-D: n = 12; subacute SCI: n = 12, chronic SCI: n = 12]). TSP in response to the foot CPT was higher in subacute compared to chronic incomplete SCI-NP, while TSP to the hand CPT was significantly higher in chronic compared to the subacute complete SCI-NP group. Evoked pain intensity during the hand CPT correlated with duration of below-level SCI-NP. The hand CPT induced widespread pronociception (lower PPT), which correlated with 7-day non-evoked (spontaneous) pain intensity in individuals with incomplete SCI-NP. Individuals with below-level NP, but not at-level NP, showed higher TSP during the foot CPT and greater hand CPT-induced L4 dermatome pronociception. Conclusions: Collectively, measurements of above and below-level temporal summation of pain and translesional-induced pronociception in the SCI-NP group highlight the role of these mechanisms in widespread central sensitization, spontaneous pain intensity, and spinothalamic tract hyperexcitability, especially in individuals diagnosed with below-level NP. Full article

Background/Objectives: Fibromyalgia (FM) is a syndrome characterized by widespread chronic pain as the primary symptom. Neurophysiological pain mechanisms, such as the function of the descending inhibitory system, are impaired in this condition. The main objective of this study was to compare the results of two paradigms to evaluate CPM in women with FM. The secondary objective was to correlate the results of each CPM paradigm with the clinical status of patients with FM. Methods: One hundred and three FM women were divided into two groups: fifty patients diagnosed with FM were assigned to the conditioned pain modulation (CPM) group using a cold pressor stimulus, and fifty-three patients were assigned to the CPM group using the ischemic pressure stimulus. The main outcome measures were pain intensity, disability, mechanical hyperalgesia, and CPM. Results: The primary analysis revealed significant differences between the results obtained from the different CPM protocols. Poorer outcomes in the cold pressor test correlated with higher pain intensity and a greater disability index. Conclusions: Pain modulation abnormalities in FM patients were evident when using either the cold pressor or ischemic pressure stimuli to establish the CPM paradigm. The cold pressor conditioning stimulus elicited a stronger response than the ischemic pressure stimulus in FM patients. Full article

The sympathetic nervous responses to cold stress are known; however, concurrent cardiovascular and ocular parameter alterations in the responses are poorly characterized. The aim of this study was to examine the influence of the cold pressor test (CPT) on cardiovascular and ocular parameters in young adult subjects. There was a total of 86 participants. The CPT was conducted by submerging each participant’s left hand in cold water (3–5 °C) for 3 min. During the CPT, systolic blood pressure, diastolic blood pressure, mean arterial pressure (MAP), and heart rate were found to be significantly increased compared to the baseline and significantly decreased compared to recovery, including the mean of the standard deviations of all normal-to-normal intervals (SDNN). In the recovery phase, the SDNN continued to decrease statistically significantly compared to the baseline and the CPT. Furthermore, the findings of this study show that the CPT impacted intra-ocular pressure (IOP), ACD, and pupil size parameters. There was a positive correlation between the MAP and IOP in both eyes during the CPT. The cold stress stimulates a sympathetic response, leading to an increase in the MAP. The pupil size increased in response to the CPT in both eyes, indicating that ocular function was increased in response to the CPT in young adults compared to baseline. In conclusion, our results suggest that in young adults, cardiovascular and ocular parameters respond to the sympathetic nervous system during the CPT. Full article