Search

Abstract: Chronic pain remains poorly managed. The integration of immersive technologies (ie, virtual reality [VR]) with neuroscience-based principles may provide effective pain treatment by targeting cognitive and affective neural processes that maintain pain and therefore potentially changing neurobiological circuits associated with pain chronification and amplification. We tested the effectiveness of a novel VR neuroscience-based therapy (VRNT) to improve pain-related outcomes in n = 31 participants with chronic back pain, evaluated against usual care (waitlist control; n = 30) in a 2-arm randomized clinical trial ( NCT04468074) . We also conducted pre-treatment and post-treatment MRI to test whether VRNT affects brain networks previously linked to chronic pain and treatment effects. Compared with the control condition, VRNT led to significantly reduced pain intensity (g = 0.63) and pain interference (g = 0.84) at post-treatment vs pre-treatment, with effects persisting at 2-week follow-up. These improvements were partially mediated by reduced kinesiophobia and pain catastrophizing. Several secondary clinical outcomes were also improved by VRNT, including disability, quality of life, sleep, and fatigue. In addition, VRNT was associated with increases in dorsomedial prefrontal functional connectivity with the superior somatomotor, anterior prefrontal and visual cortices, and decreased white matter fractional anisotropy in the corpus callosum adjacent to the anterior cingulate, relative to the control condition. Thus, VRNT showed preliminary efficacy in significantly reducing pain and improving overall functioning, possibly through changes in somatosensory and prefrontal brain networks., (Copyright © 2024 International Association for the Study of Pain.)

Introduction: Current guidelines for pain treatment recommend a personalized, multimodal and interdisciplinary approach as well as the use of a combination of drug and non-drug therapies. Risk factors for chronification should already be reduced in patients with acute pain, e.g., after surgery or trauma. Auricular vagus nerve stimulation (aVNS) could be an effective non-drug therapy in the multimodal treatment of chronic and acute pain. The aim of this systematic review and meta-analysis is to evaluate the clinical efficacy and safety of aVNS in treating chronic and acute pain conditions. Methods: A systematic literature search was performed regarding the application of auricular electrical stimulation in chronic and acute pain. Studies were classified according to their level of evidence (Jadad scale), scientific validity and risk of bias (RoB 2 tool) and analyzed regarding indication, method, stimulation parameters, duration of treatment and efficacy and safety. A meta-analysis on (randomized) controlled trials (using different comparators) was performed for chronic and acute pain conditions, respectively, including subgroup analysis for percutaneous (pVNS—needle electrodes) and transcutaneous (tVNS—surface electrodes) aVNS. The visual analog pain scale (VAS) was defined as primary efficacy endpoint. Results: A total of n = 1496 patients were treated with aVNS in 23 identified and analyzed studies in chronic pain, 12 studies in acute postoperative pain and 7 studies in experimental acute pain. Of these, seven studies for chronic pain and six studies for acute postoperative pain were included in the meta-analysis. In chronic pain conditions, including back pain, migraine and abdominal pain, a statistically significant reduction in VAS pain intensity for active compared to sham aVNS or control treatment with an effect size Hedges' g/mean difference of − 1.95 (95% confidence interval [CI]: − 3.94 to 0.04, p = 0.008) could be shown and a more favorable effect in pVNS compared to tVNS (− 5.40 [− 8.94; − 1.85] vs. − 1.00 [− 1.55; − 0.44]; p = 0.015). In acute pain conditions, single studies showed significant improvements with aVNS, e.g., in kidney donor surgery or tonsillectomy but, overall, a non-statistically significant reduction in VAS pain intensity for active compared to sham aVNS or control with − 0.70 [− 2.34; 0.93] (p = 0.15) could be observed in the meta-analysis. In acute pain results vary greatly between studies depending especially on co-medication and timepoints of assessment after surgery. A significant reduction in analgesics or opiate intake was documented in most studies evaluating this effect in chronic and acute pain. In 3 of the 12 randomized controlled trials in patients with chronic pain, a sustainable pain reduction over a period of up to 12 months was shown. Overall, aVNS was very well tolerated. Conclusion: This systematic review and meta-analysis indicate that aVNS can be an effective and safe non-drug treatment in patients with specific chronic and acute postoperative pain conditions. Further research is needed to identify the influence of simulation parameters and find optimal and standardized treatment protocols while considering quality-of-life outcome parameters and prolonged follow-up periods. A more standardized approach and harmonization in study designs would improve comparability and robustness of outcomes. [ABSTRACT FROM AUTHOR]

Background: Transcranial direct current stimulation (tDCS) might modulate neural activity and promote neural plasticity in patients with fibromyalgia (FM). This multi-group randomized clinical trial compared home-based active tDCS (HB-a-tDCS) on the left dorsolateral prefrontal cortex (l-DLPFC) or home-based sham tDCS (HB-s-tDCS), and HB-a-tDCS or HB-s-tDCS on the primary motor cortex (M1) in the connectivity analyses in eight regions of interest (ROIs) across eight resting-state electroencephalography (EEG) frequencies. Methods: We included 48 women with FM, aged 30 to 65, randomly assigned to 2:1:2:1 to receive 20 sessions during 20 minutes of HB-a-tDCS 2mA or HB-s-tDCS, over l-DLPFC or M1, respectively. EEG recordings were obtained before and after treatment with eyes open (EO) and eyes closed (EC). Results: In the EC condition, comparing pre to post-treatment, the HB-a-tDCS on l-DLPFC decreased the lagged coherence connectivity in the delta frequency band between the right insula and left anterior cingulate cortex (ACC) (t = -3.542, p =.048). The l-DLPFC HB-a-tDCS compared to HB-s-tDCS decreased the lagged coherence connectivity in the delta frequency band between the right insula and left ACC (t = -4.000, p =.017). In the EO condition, the l-DLPFC HB-a-tDCS compared to M1 HB-s-tDCS increased the lagged coherence connectivity between the l-DLPFC and left ACC in the theta band (t = -4.059, p =.048). Regression analysis demonstrated that the HB-a-tDCS effect on the l-DLPFC was positively correlated with sleep quality. On the other hand, the HB-a-tDCS on l-DLPFC and HB-s-tDCS on M1 were positively correlated with pain catastrophizing. Conclusions: These results show that HB-a-tDCS affects the neural connectivity between parts of the brain that control pain's emotional and attentional aspects, which are most noticeable at lower EEG frequencies in a rest state. This effect on neural oscillations could serve as a neural marker associated with its efficacy in alleviating fibromyalgia symptoms. Clinical trial registration: identifier [NCT03843203]. [ABSTRACT FROM AUTHOR]

Background: Mind-body treatments can improve coping mechanisms to deal with pain, improve the quality of life of patients with fibromyalgia syndrome (FMS), and reduce perceived pain in some cases. However, responses to these treatments are highly variable, the mechanisms underpinning them remain unclear, and reliable predictors of treatment response are lacking. We employed resting-state blood oxygen level-dependent (rsBOLD) functional magnetic resonance imaging (fMRI) to examine changes in brain functional connectivity (FC) following mind-body treatment that may relate to and predict pain relief. Methods: We recruited patients with FMS who underwent either mindfulnessbased stress reduction (MBSR; n = 18) or a psychoeducational program (FibroQoL; n = 22) and a treatment-as-usual FMS group (TAU; n = 18). We collected rsBOLD data, alongside subjective pain, anxiety, depression, and catastrophizing measures prior to and following treatments. We examined behavioral changes and FC changes in the salience network (SN) and sensorimotor network (SMN) and performed regression analyses to identify predictors for treatment response. Results: The MBSR and FibroQoL groups experienced significant reductions in pain catastrophizing. After treatment, the FC of the sensorimotor cortex with the rest of the SMN became significantly reduced in the MBSR group compared to the TAU group. The FC between the SN and the SMN at baseline was negatively correlated with pain reductions following MBSR but positively correlated with pain reductions in the FibroQoL group. These results yielded large to very large effect sizes. Following MBSR, only for those patients with lower baseline SMN-SN FC, minutes of mindfulness practice were positively associated with clinical improvement (small to medium effect size). Conclusions: Different mind-body treatments are underpinned by discrete brain networks. Measures of the functional interplay between SN and SMN have the potential as predictors of mind-body treatment response in patients with FMS. [ABSTRACT FROM AUTHOR]

Purpose: Neuroimaging studies employing analyses dependent on regional assumptions and specific neuronal circuits could miss characteristics of whole-brain structural connectivity critical to the pathophysiology of fibromyalgia (FM). This study applied the whole-brain graph-theoretical approach to identify whole-brain structural connectivity disturbances in FM., Methods: This cross-sectional study used probabilistic diffusion tractography and graph theory analysis to evaluate the topological organization of brain white matter networks in 20 patients with FM and 20 healthy controls (HCs). The relationship between brain network metrics and clinical variables was evaluated., Results: Compared with HCs, FM patients had lower clustering coefficient, local efficiency, hierarchy, synchronization, and higher normalized characteristic path length. Regionally, patients demonstrated a significant reduction in nodal efficiency and centrality; these regions were mainly located in the prefrontal, temporal cortex, and basal ganglia. The network-based statistical analysis (NBS) identified decreased structural connectivity in a subnetwork of prefrontal cortex, basal ganglia, and thalamus in FM. There was no correlation between network metrics and clinical variables (false discovery rate corrected)., Conclusions: The current research demonstrated disrupted topological architecture of white matter networks in FM. Our results suggested compromised neural integration and segregation and reduced structural connectivity in FM., (© 2023. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)

Background: Parasympathetic tone activity (PTA) in response to nociceptive stimulus in conscious non‐sedated horses is unknown. Objectives: Study PTA, heart rate (HR), and horse grimace scale (HGS) at rest and during mechanical nociceptive stimulation. Animals: Ninety healthy young adult horses (females, males): 30 each of Friesians, Quarter Horses, and Warmbloods. Methods: Prospective control study. The study consisted of habituation to equipment (Day 1), baseline recordings (Days 2 and 3), and nociceptive testing applying mild pressure to the metacarpus (Day 4). Parasympathetic tone, HR, and HGS were recorded simultaneously on Days 2 to 4. Each study lasted 30 minutes and was done in triplicate at 3 different time points per day. Results: Baseline PTA was not different among breeds. It decreased in Warmbloods and Quarter Horses during placement of the stimulus device without stimulation (P <.01). A significant decrease in PTA (P <.001) occurred during nociceptive stimulus (marked in Quarter Horses, intermediate in Warmbloods, and mild in Friesians). Heart rate and HGS increased significantly (P <.001) during the stimulus in all breeds but returned to baseline poststimulation. Friesians required higher pressure (P <.05) to elicit an aversive response to the stimulus. Conclusions: Horses' PTA, HR, and HGS change in response to a mild mechanical nociceptive stimulus with Friesians showing less variation. Stress induced a decrease in PTA in Quarter Horses and Warmbloods but not in Friesians. Friesians appeared to be more tolerant to pain based on PTA, HR, and HGS findings compared with other breeds. [ABSTRACT FROM AUTHOR]

Copyright of Der Schmerz is the property of Springer Nature and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)

Background: Parkinson's disease (PD) is characterized by a range of motor symptoms as well as documented sensory dysfunction. This sensory dysfunction can present itself either as a "pure" sensory disturbance or as a consequence of sensory-motor integration within the central nervous system. This study aims to investigate changes in the functional connectivity of the primary somatosensory cortex (S1) and its clinical significance in Parkinson's disease (PD), an area that has received limited attention in previous neuroimaging studies. Methods: This study included thirty-three patients with PD and thirty-four healthy controls (HCs). Clinical evaluations were conducted to assess the clinical manifestations, severity, and functional capacity of all the patients. Resting-state functional MRI (fMRI) was employed to evaluate the functional connectivity of six paired S1 subregions in the participants. Seed-based correlation (SBC) analysis was utilized to construct the correlation matrix among the subregions and to generate connectivity maps between the subregions and the remaining brain voxels. Finally, the study employed partial least-squares (PLS) correlation analysis to investigate the association between modified functional connectivity and clinical characteristics in PD patients. Results: In the correlation matrix, patients with PD demonstrated a notable decrease in functional connectivity across various S1 subregions in comparison to HCs (p< 0.001, corrected using network-based methods). In connectivity maps, hypo-connectivity was primarily observed in the sensorimotor network as common patterns (p< 0.001, corrected for false discovery rate) and in the default mode network (DMN) as distinct patterns. Moreover, this study identified a negative association between the correlation matrix within S1 subregions and the scores for axial symptoms and postural instability/gait difficulty (PIGD) in PD patients. Nevertheless, a direct relationship between the connectivity maps of S1 subregions and clinical assessment scales was not established. Conclusion: This study offers novel insights into the neurobiological mechanisms that contribute to S1 dysfunction in PD, highlighting the significant involvement of S1 hypo-connectivity in the motor disturbances observed in PD patients. [ABSTRACT FROM AUTHOR]

Fibromyalgia (FMS) is generally associated with neuropathic pain (NP) because of the neuropathic symptoms frequently observed in patients with FMS. The aim of the study is to evaluate the neuropathic component of FMS with the painDETECT (PD-Q) and Douler Neuropathic 4 (DN4) scales. Female patients diagnosed as FMS according to the American College of Rheumatology’s 2010 FMS criteria and female healthy volunteers are included in the study. After demographic evaluation, the patients and volunteers were asked to fill out Visual Analog Score (VAS), PD-Q, and DN4 scale forms. The Fibromyalgia Impairment Questionnaire (FIQ) evaluated life quality and function. There were 66 patients in the FMS group with a mean age of 46.16± 10.66 and 61 patients in the control group with a mean age of 44.93± 12.72. It was determined that there was a significant difference between the VAS, PD-Q, and DN4 values of FMS and control groups (tVAS = 5,025 p < 0.05, t PD-Q = 5,025 p < 0.05, tDN4 = 7,885 p < 0.05). The mean pain score (VAS) and NP level (DN4 and PD-Q) of FMS patients were significantly higher than healthy individuals. In addition, it was determined that VAS (p = 0.001) and PD-Q (p = 0.046) values were found to be significant predictors of the FIQ values. FMS patients may have pain with a neuropathic component, and it seems useful to evaluate neuropathic characteristics with PD-Q and DN4. If the components of pain are researched carefully, more improvement may be achieved in pain and functional capacity [ABSTRACT FROM AUTHOR]

BACKGROUND: Central sensitization cannot be demonstrated directly in humans. Therefore, studies used different proxy markers (signs, symptoms and tools) to identify factors assumed to relate to central sensitization in humans, that is, Human Assumed Central Sensitization (HACS). The aims of this systematic review were to identify non-invasive objective markers of HACS and the instruments to assess these markers in patients with fibromyalgia (FM). METHODS: A systematic review was conducted with the following inclusion criteria: (1) adults, (2) diagnosed with FM, and (3) markers and instruments for HACS had to be non-invasive. Data were subsequently extracted, and studies were assessed for risk of bias using the quality assessment tools developed by the National Institute of Health. RESULTS: 78 studies (n = 5234 participants) were included and the findings were categorized in markers identified to assess peripheral and central manifestations of HACS. The identified markers for peripheral manifestations of HACS, with at least moderate evidence, were pain after-sensation decline rates, mechanical pain thresholds, pressure pain threshold, sound 'pressure' pain threshold, cutaneous silent period, slowly repeated evoked pain sensitization and nociceptive flexion reflex threshold. The identified markers for central manifestations of HACS were efficacy of conditioned pain modulation with pressure pain conditioning and brain perfusion analysis. Instruments to assess these markers are: pin-prick stimulators, cuff-algometry, repetitive pressure stimulation using a pressure algometer, sound, electrodes and neuroimaging techniques. CONCLUSIONS: This review provides an overview of non-invasive markers and instruments for the assessment of HACS in patients with FM. Implementing these findings into clinical settings may help to identify HACS in patients with FM. [ABSTRACT FROM AUTHOR]

Background: Chronic postsurgical pain (CPP) markedly impairs patients' quality of life. Research has shown that chronic stress may extend incisional nociception in male mice. Dopaminergic (DAergic) neurons in the ventral tegmental area (VTA) are integral to stress-related mental disorders (including major depressive disorder, anxiety disorders, and PTSD) and pain. However, the impact of chronic social defeat stress (CSDS) on mesolimbic dopamine (DA) transmission in the development of CPP is yet to be established. It remains uncertain whether the dopamine signals in the rostral anterior cingulate cortex (rACC), which regulate pain, derive from the VTA. This study aims to explore the role of VTA-rACC dopaminergic circuits in a mouse model of CPP induced by CSDS. Methods: We conducted CSDS on C57BL/6 J wild-type male mice (n = 12–16 mice/group) and DAT-cre male mice (n = 10–12 mice/group). After 10 days of CSDS, a left posterior plantar incision was made to establish a mouse model of CPP. Paw withdrawal thresholds (PWTs) were evaluated using Von-Frey fibre stimulation. The open field test (OFT) and elevated plus maze test (EPM) were used to assess pain-related negative emotions. We used immunofluorescence staining and Western Blot to analyse D1, D2, c-Fos, and TH expression. DAergic fibre projections in the VTA-rACC neural pathway were traced using retrograde tracing and immunofluorescence staining. Optogenetics and Chemogenetics were employed to manipulate DAergic neurons in the VTA and their axons in the rACC. Results: The ipsilateral PWTs in male C57BL/6 J mice significantly decreased after surgery, returning to baseline after seven days. Conversely, in CSDS mice, ipsilateral PWTs remained reduced for at least 30 days post-incision. A significant reduction in TH-positive neurons expressing c-Fos in the VTA of CPP mice was observed 15 days post-incision. Activating DAergic neurons significantly improved ipsilateral PWTs and locomotor performance in the OFT and EPM in CPP mice post-incision. Additionally, D1 expression in the rACC was found to decrease in CPP mice, and this reduction counteracted the increase in PWTs caused by activating DAergic neuron axon terminals in the rACC. Conclusion: CSDS results in chronicity of postsurgical nociception and anxiety-like negative emotions, with alterations in DA transmission playing a role in CPP. Specific activation of DAergic neurons mitigates nociceptive responses and anxiety-like bahaviors, possibly mediated by D1 receptors in the rACC. [ABSTRACT FROM AUTHOR]

Objective: Abnormal central pain processing is a leading cause of pain in fibromyalgia (FM) and is perceptually characterized with the psychophysical measure of temporal summation of pain (TSP). TSP is the perception of increasingly greater pain in response to repetitive or tonic noxious stimuli. Previous neuroimaging studies have used static (i.e., summary) measures to examine the functional magnetic resonance imaging (fMRI) correlates of TSP in FM. However, functional brain activity rapidly and dynamically reorganizes over time, and, similarly, TSP is a temporally evolving process. This study was undertaken to demonstrate how a complete understanding of the neural circuitry supporting TSP in FM thus requires a dynamic measure that evolves over time., Methods: We utilized novel methods for analyzing dynamic functional brain connectivity in patients with FM in order to examine how TSP-associated fluctuations are linked to the dynamic functional reconfiguration of the brain. In 84 FM patients and age- and sex-matched healthy controls, we collected high-temporal-resolution fMRI data during a resting state and during a state in which sustained cuff pressure pain was applied to the leg., Results: FM patients experienced greater TSP than healthy controls (mean ± SD TSP score 17.93 ± 19.24 in FM patients versus 9.47 ± 14.06 in healthy controls; P = 0.028), but TSP scores varied substantially between patients. In the brain, the presence versus absence of TSP in patients with FM was marked by more sustained enmeshment between sensorimotor and salience networks during the pain period. Furthermore, dynamic enmeshment was noted solely in FM patients with high TSP, as interactions with all other brain networks were dampened during the pain period., Conclusion: This study elucidates the dynamic brain processes underlying facilitated central pain processing in FM. Our findings will enable future investigation of dynamic symptoms in FM., (© 2021 American College of Rheumatology.)

Fibromyalgia (FM) is a condition characterized by chronic widespread pain whose pathogenesis is still not fully defined. Evidence based on structural and functional neuroimaging methods, electrophysiological, and morphological - skin biopsy - features demonstrated a central and peripheral nervous system involvement. A dysfunction in nociceptive inputs processing at the central level was highlighted as the primary cause of FM, but other data coming from different laboratories contributed to emphasize again the peripheral origin of FM. In fact, small fibers neuropathy (SFN) was observed in a large number of patients submitted to skin biopsy. The complex interaction between central and peripheral factors is opening a new scenario about the management of this neurological disorder. Whether proximal SFN is an initiating event leading to FM or is the consequence of stress-related insular hyper excitability remains unclear. Mild sufferance of peripheral afferents could function as a trigger for an exaggerated response of the so-called "salience matrix" in predisposed individuals. On the other side, the intriguing hypothesis rising from animal models could indicate that the cortical hyper function could cause peripheral small afferent damage. The research should go on the genetic origin of such peripheral and central abnormalities, the acquired facilitating factors, and the presence of different phenotypes in order to search for efficacious treatments, which are still lacking., (© 2021. Fondazione Società Italiana di Neurologia.)

Gastrointestinal (GI) disorders, which extend from the esophagus to the anus, are the most common diseases of the GI tract. Among these disorders, pain, encompassing both abdominal and visceral pain, is a predominant feature, affecting the patients' quality of life and imposing a substantial financial burden on society. Pain signals originating from the gut intricately shape brain dynamics. In response, the brain sends appropriate descending signals to respond to pain through neuronal inhibition. However, due to the heterogeneous nature of the disease and its limited pathophysiological understanding, treatment options are minimal and often controversial. Consequently, many patients with GI disorders use complementary and alternative therapies such as neuromodulation to treat visceral pain. Neuromodulation intervenes in the central, peripheral, or autonomic nervous system by alternating or modulating nerve activity using electrical, electromagnetic, chemical, or optogenetic methodologies. Here, we review a few emerging noninvasive neuromodulation approaches with promising potential for alleviating pain associated with functional dyspepsia, gastroparesis, irritable bowel syndrome, inflammatory bowel disease, and non-cardiac chest pain. Moreover, we address critical aspects, including the efficacy, safety, and feasibility of these noninvasive neuromodulation methods, elucidate their mechanisms of action, and outline future research directions. In conclusion, the emerging field of noninvasive neuromodulation appears as a viable alternative therapeutic avenue for effectively managing visceral pain in GI disorders. [ABSTRACT FROM AUTHOR]

Background: Temporomandibular disorders (TMD) are characterized by pain and impaired masticatory functions. The Integrated Pain Adaptation Model (IPAM) predicts that alterations in motor activity may be associated with increased pain in some individuals. The IPAM highlights the diversity of patients' responses to orofacial pain and suggests that such diversity is related to the sensorimotor network of the brain. It remains unclear whether the pattern of brain activation reflects the diversity of patients' responses underlying the association between mastication and orofacial pain. Objective: This meta‐analysis aims to compare the spatial pattern of brain activation, as the primary outcome of neuroimaging studies, between studies of mastication (i.e. Study 1: mastication of healthy adults) and studies of orofacial pain (i.e. Study 2: muscle pain in healthy adults and Study 3: noxious stimulation of the masticatory system in TMD patients). Methods: Neuroimaging meta‐analyses were conducted for two groups of studies: (a) mastication of healthy adults (Study 1, 10 studies) and (b) orofacial pain (7 studies), including muscle pain in healthy adults (Study 2) and noxious stimulation of the masticatory system in TMD patients (Study 3). Consistent loci of brain activation were synthesized using Activation Likelihood Estimation (ALE) with an initial cluster‐forming threshold (p <.05) and a threshold of cluster size (p <.05, familywise error‐corrected). Results: The orofacial pain studies have shown consistent activation in pain‐related regions, including the anterior cingulate cortex and the anterior insula (AIns). A conjunctional analysis of mastication and orofacial pain studies showed joint activation at the left AIns, the left primary motor cortex and the right primary somatosensory cortex. Conclusion: The meta‐analytical evidence suggests that the AIns, as a key region in pain, interoception and salience processing, contributes to the pain‐mastication association. These findings reveal an additional neural mechanism of the diversity of patients' responses underlying the association between mastication and orofacial pain. [ABSTRACT FROM AUTHOR]

Objective: Subjective cognitive dysfunction (SCD) affects 55–75% of individuals with fibromyalgia (FM), but those reporting cognitive difficulties often lack corresponding objective deficits. Symptoms of depression and anxiety are prevalent in FM and may account for part of this discrepancy. This study was undertaken to investigate whether momentary (within‐day, across 7 days) changes in mood moderate the relationship between within‐the‐moment SCD and mental processing speed performance. Methods: A total of 50 individuals with FM (mean age 44.8 years, mean education 15.7 years, 88% female, 86% White) completed momentary assessments of subjective cognitive functioning, depressive and anxious symptoms, and a test of processing speed. Assessments were completed 5 times per day for 8 consecutive days on a study‐specific smartphone application. Results: Momentary ratings of SCD were positively associated with mean reaction time (P < 0.001) and variability of processing speed (P = 0.02). Depressive symptoms moderated the relationship between SCD and processing speed, with lower correspondence when depressive symptoms were higher (P = 0.03). A similar moderating effect was demonstrated for both depression (P = 0.02) and anxiety (P = 0.03) on the association between SCD and variability in processing speed performance. Conclusion: Individuals with FM may have more accurate self‐perception of momentary changes in mental processing speed during periods of less pronounced mood symptoms based on their corresponding objective processing speed performance. However, during moments of heightened depression and anxiety, we found increasingly less correspondence between SCD and objective performance, suggesting that psychological symptoms may play an important role in self‐perception of cognitive dysfunction in FM as it relates to mental processing speed. [ABSTRACT FROM AUTHOR]

As cardiac vagal control is a hallmark of good health and self-regulatory capacity, researchers are seeking ways to increase vagally mediated heart rate variability (vmHRV) in an accessible and non-invasive way. Findings with transcutaneous auricular vagus nerve stimulation (taVNS) have been disappointing in this respect, as its effects on vmHRV are inconsistent at best. It has been speculated that combining taVNS with other established ways to increase vmHRV may produce synergistic effects. To test this idea, the present study combined taVNS with slow breathing in a cross-over design. A total of 22 participants took part in two sessions of breathing at 6 breaths/min: once combined with taVNS, and once combined with sham stimulation. Electrical stimulation (100 Hz, 400 µs) was applied during expiration, either to the tragus and cavum conchae (taVNS) or to the earlobe (sham). ECG was recorded during baseline, 20-minutes of stimulation, and the recovery period. Frequentist and Bayesian analyses showed no effect of taVNS (in comparison to sham stimulation) on the root mean square of successive differences between normal heartbeats, mean inter-beat interval, or spectral power of heart rate variability at a breathing frequency of 0.1 Hz. These findings suggest that expiratory-gated taVNS combined with the stimulation parameters examined here does not produce acute effects on vmHRV during slow breathing. [ABSTRACT FROM AUTHOR]

Copyright of Zeitschrift für Rheumatologie is the property of Springer Nature and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)

Key message: Reconstruction of needle dynamics reveals prolonged drought legacy effects on crown condition that represent early warnings of drought-induced dieback in Scots pine. Understanding the mechanisms of drought-induced forest dieback and tree mortality is a priority for predicting forest responses to climate change. However, long-term information on drought impacts on crown dynamics and how it relates to tree water and carbon economy is still lacking. Comparing declining and non-declining Scots pines at the same site, we quantified primary and secondary growth and intrinsic water-use efficiency (WUEi). Further, we reconstructed the needle production and the annual total number of needles using the Needle Trace Method. Here, we reconstructed the apical needles through the assessment of 2460 longitudinal sections. We fitted partial least squares regression models to assess climate influence on primary and secondary growth and needle dynamics, and then linear mixed models using climate covariates and discerning between health status in the 1975–2016 period. Finally, we analyzed drought legacy effects applying a Bayesian hierarchical framework. We detected the highest differences between health tree classes in the annual total number of needles during the warm-dry 1980s. Declining trees responded more negatively to climate than non-declining conspecifics and showed a higher variability of drought legacy effects. We found significant drought legacy effects in the annual total number of needles up to 3 years after a drought. The warm, dry 1980s, that preceded the dieback, showed the highest δ13C values since the 1970s. Declining trees showed higher WUEi than non-declining trees from the 2000s onwards. Our study sheds light on the major role of needle dynamics in dieback episodes and illustrates how past drops in needle production may be interpreted as early warnings of drought-induced dieback in Scots pine. [ABSTRACT FROM AUTHOR]

Copyright of Health Sciences Journal / Revista Ciências em Saúde is the property of Hospital de Clinicas de Itajuba - Associacao de Integracao Social de Itajuba and its content may not be copied or emailed to multiple sites or posted to a listserv without the copyright holder's express written permission. However, users may print, download, or email articles for individual use. This abstract may be abridged. No warranty is given about the accuracy of the copy. Users should refer to the original published version of the material for the full abstract. (Copyright applies to all Abstracts.)

The ability to adaptively guide behaviour requires the integration of external information with internal motivational factors. Decision-making capabilities can be impaired by acute stress and is often exacerbated by chronic pain. Chronic neuropathic pain patients often present with cognitive dysfunction, including impaired decision-making. The mechanisms underlying these changes are not well understood but may include altered monoaminergic transmission in the brain. In this study we investigated the relationships between dopamine, serotonin, and their metabolites in key brain regions that regulate motivated behaviour and decision-making. The neurochemical profiles of the medial prefrontal cortex, orbital prefrontal cortex, and nucleus accumbens were analysed using HPLC in rats that received a chronic constriction injury (CCI) of the right sciatic nerve and an acute stress (15-min restraint), prior to an outcome devaluation task. CCI alone significantly decreased dopamine but not serotonin concentrations in the medial prefrontal cortex. By contrast, restraint stress acutely increased dopamine in the medial prefrontal cortex, and the nucleus accumbens; and increased serotonin in the medial prefrontal cortex 2 h later. The sustained dopaminergic and serotonergic responses to acute stress highlight the importance of an animal's ability to mount an effective coping response. In addition, these data suggest that the impact of nerve injury and acute stress on outcome-devaluation occurs independently of dopaminergic and serotonergic transmission in the medial prefrontal cortex, orbital prefrontal cortex and nucleus accumbens of rats. [ABSTRACT FROM AUTHOR]

This study evaluated the antihyperalgesic and anti-inflammatory effects of percutaneous vagus nerve electrical stimulation (pVNS) by comparing the effects of alternating and random frequencies in an animal model of persistent inflammatory hyperalgesia. The model was induced by Freund's complete adjuvant (CFA) intraplantar (i.pl.) injection. Mice were treated with different protocols of time (10, 20, or 30 min), ear laterality (right, left or both), and frequency (alternating or random). Mechanical hyperalgesia was evaluated, and some groups received i.pl. WRW4 (FPR2/ALX antagonist) to determine the involvement. Edema, paw surface temperature, and spontaneous locomotor activity were evaluated. Interleukin-1β, IL-6, IL-10, and IL4 levels were verified by enzyme-linked immunosorbent assay. AnxA1, FPR2/ALX, neutrophil, M1 and M2 phenotype macrophage, and apoptotic cells markers were identified using western blotting. The antihyperalgesic effect pVNS with alternating and random frequency effect is depending on the type of frequency, time, and ear treated. The pVNS random frequency in the left ear for 10 min had a longer lasting antihyperalgesic effect, superior to classical stimulation using alternating frequency and the FPR2/ALX receptor was involved in this effect. There was a reduction in the levels of pro-inflammatory cytokines and an increase in the immunocontent of AnxA1 and CD86 in mice paw. pVNS with a random frequency in the left ear for 10 min showed to be optimal for inducing an antihyperalgesic effect. Thus, the random frequency was more effective than the alternating frequency. Therefore, pVNS may be an important adjunctive treatment for persistent inflammatory pain. [ABSTRACT FROM AUTHOR]

Purpose of Review: Neuromodulation for the management of atrial fibrillation (AF) has been a topic of increased interest in recent years; however, there are still challenges regarding which patients would benefit most from these treatments and how we can optimize neuromodulatory procedures to have the greatest effect. We aimed to summarize the current knowledge on optimization of neuromodulatory therapies for AF and discuss the challenges and future directions for research in this area. Recent Findings: In recent years, the switch from invasive to non-invasive neuromodulatory approaches has made it possible to conduct clinical studies using at-home self-administrated devices to evaluate long-term effects. In this regard, transcutaneous auricular vagus nerve stimulation (ta-VNS) has received more attention, to the extent that clinical studies have determined its beneficial effects on reducing AF burden and atrial alternans in paroxysmal AF patients within 6 months. P-wave alternans, reflecting beat to beat variation in P wave amplitude, has been recently introduced as a predictive biomarker for acute and chronic responses to ta-VNS that can be useful in optimizing patient selection and stimulation parameters. Summary: Optimizing patient selection and stimulation parameters is critical for maximizing the patient-specific, on-target favorable effects of neuromodulatory treatments while minimizing their off-target effects. Identifying biomarkers that can predict acute and chronic responses to neuromodulatory treatment is critical in achieving optimal neuromodulation. [ABSTRACT FROM AUTHOR]

Objectives: Mindfulness-based interventions (MBIs) have emerged as promising prophylactic episodic migraine treatments. The present study investigated biopsychosocial predictors and outcomes associated with formal, daily-life meditation practice in migraine patients undergoing MBI, and whether augmented mindfulness mechanistically underlies change. Methods: Secondary analyses of clinical trial data comparing a 12-week enhanced mindfulness-based stress reduction course (MBSR + ; n = 50) to stress management for headache (SMH; n = 48) were conducted. Results: Pre-treatment mesocorticolimbic system functioning (i.e., greater resting state ventromedial prefrontal cortex-right nucleus accumbens [vmPFC-rNAC] functional connectivity) predicted greater meditation practice duration over MBSR + (r = 0.58, p = 0.001), as well as the change in headache frequency from pre- to post-treatment (B = − 12.60, p = 0.02) such that MBSR + participants with greater vmPFC-rNAC connectivity showed greater reductions in headache frequency. MBSR + participants who meditated more showed greater increases in mindfulness (B = 0.52, p = 0.02) and reductions in the helplessness facet of pain catastrophizing (B = − 0.13, p = 0.01), but not headache frequency, severity, or impact. Augmented mindfulness mediated reductions in headache impact resulting from MBSR + , but not headache frequency. Conclusions: Mesocorticolimbic system function is implicated in motivated behavior, and thus, motivation-enhancing interventions might be delivered alongside mindfulness-based training to enhance meditation practice engagement. Formal, daily-life meditation practice duration appears to benefit pain-related cognitions, but not clinical pain, while mindfulness emerges as a mechanism of MBIs on headache impact, but not frequency. Further research is needed to investigate the day-to-day effects of formal, daily-life meditation practice on pain, and continue to characterize the specific mechanisms of MBIs on headache outcomes. Preregistration: This study is not preregistered. [ABSTRACT FROM AUTHOR]

Over 50 million Americans endure chronic pain where many do not receive adequate treatment and self-medicate to manage their pain by taking substances like opioids and cannabis. Research has shown high comorbidity between chronic pain and substance use disorders (SUD) and these disorders share many common neurobiological underpinnings, including hypodopaminergic transmission. Drugs commonly used for self-medication such as opioids and cannabis relieve emotional, bothersome components of pain as well as negative emotional affect that perpetuates misuse and increases the risk of progressing towards drug abuse. However, the causal effect between chronic pain and the development of SUDs has not been clearly established. In this review, we discuss evidence that affirms the proposition that chronic pain is a risk factor for the development of opioid and cannabis use disorders by outlining the clinical evidence and detailing neurobiological mechanisms that link pain and drug misuse. Central to the link between chronic pain and opioid and cannabis misuse is hypodopaminergic transmission and the modulation of dopamine signaling in the mesolimbic pathway by opioids and cannabis. Moreover, we discuss the role of kappa opioid receptor activation and neuroinflammation in the context of dopamine transmission, their contribution to opioid and cannabis withdrawal, along with potential new treatments., (© 2024. The Author(s), under exclusive licence to Springer-Verlag GmbH Austria, part of Springer Nature.)

Objectives: Migraine is one of the most frequent clinical manifestations of hypermobile Ehlers-Danlos syndrome (hEDS). The comorbidity between these two diseases has been only partially investigated. We aimed to observe whether neurophysiological alterations described inmigraineurs in visual evoked potentials (VEPs) were present in hEDS patients with migraine. Methods: We enrolled 22 hEDS patients with migraine (hEDS) and 22 non-hEDS patients withmigraine (MIG), with and without aura (according to ICHD-3), as well as 22 healthy controls (HC). Repetitive pattern reversal (PR)-VEPs were recorded in basal conditions in all participants. During uninterrupted stimulation, 250 cortical responses were recorded (4,000Hz sample rate) and divided into epochs of 300ms after the stimulus. Cerebral responses were divided into five blocks. The habituation was calculated as the slope interpolating the amplitudes in each block, for both the N75-P100 and P100-N145 components of PR-VEP. Results: We observed a significant habituation deficit of the P100-N145 component of PR-VEP in hEDS compared to HC (p = 0.002), unexpectedly more pronounced than in MIG. We observed only a slight habituation deficit of N75-P100 in hEDS, with a slope degree that was intermediate between MIG and HC. Discussion: hEDS patients withmigraine presented an interictal habituation deficit of both VEPs components like MIG. Pathophysiological aspects underlying the pathology could account for the peculiar pattern of habituation in hEDS patients withmigraine characterized by a pronounced habituation deficit in the P100-N145 component and a less clear-cut habituation deficit in the N75-P100 component with respect to MIG. [ABSTRACT FROM AUTHOR]

Germination at low spring temperatures may offer a competitive advantage for the growth and survival of plant species inhabiting temperate forest ecosystems. Pinus koraiensis is a dominant species in temperate forests of northeastern China. Its seeds exhibit primary morphophysiological dormancy following dispersal in autumn, limiting natural or artificial regeneration: direct seeding and planting seedlings in spring. The aim of this study was to determine the optimum cold stratification temperature that induces germination to increase towards lower temperatures. Seeds from two populations (Changbaishan and Liangshui) were cold stratified at 0, 5 and 10 °C. Germination to incubation temperatures (10/5, 20/10, 25/15 and 30/20 °C; 14/10 h day/night) were determined after 2 and 4 weeks, and 5.5 and 6.5 months of cold stratification. After 5.5 months, approximately 68–91% of seeds from both populations germinated at incubation temperatures of 25/15 °C and 30/20 °C, regardless of cold stratification temperatures. When the cold stratification temperature was reduced to 0 °C and the period increased to 6.5 months, germination at 10/5 °C significantly improved, reaching 37% and 64% for the Changbaishan and Liangshui populations, respectively. After 6.5 months of cold stratification, there was a significant linear regression between cold stratification temperatures and germination at 10/5 °C. The range in temperatures allowing for germination gradually expanded to include lower temperatures with decreasing cold stratification temperatures from 10 to 5 °C and further to 0 °C. [ABSTRACT FROM AUTHOR]

Background Some women with breast implants report systemic and cognitive symptoms known as breast implant illness (BII), which are very similar to those of fibromyalgia. Functional MRI (fMRI) has shown altered brain activity in fibromyalgia patients. Objectives The aim of this pilot study was to investigate whether brain alterations could be observed in BII patients by fMRI. Methods Women aged 18 to 76 with silicone breast implants for cosmetic reasons were recruited through a Dutch online BII support organization (MKS) and through the Maastricht University Medical Center. Study participants comprised 12 women with BII and 12 women without symptoms. Participants completed questionnaires regarding demographic characteristics, medical history, psychosocial complaints (Four-Dimensional Symptom Questionnaire), cognitive failure (Mini–Mental State Examination), and pain intensity and pain-related disability (Chronic Pain Grade Scale). Subsequently, brain images of all participants were obtained by resting-state fMRI and diffusion tensor imaging in a 3-T MRI scanner (Siemens Medical System, Erlangen, Germany). Results Eleven BII patients and 12 healthy controls were included in the analysis. Baseline characteristics were similar in the 2 groups and the mean silicone exposure was 15 years. Patients scored significantly higher than controls on both pain intensity and disability. Patients scored worse on depression, somatization, distress, and anxiety compared with asymptomatic women. Mini–Mental State Examination scores were normal. However, the analyses of both functional connectivity and structural integrity showed no significant differences between the 2 groups. Conclusions This pilot study showed no evidence of brain alterations in BII patients. However, patients scored significantly worse on psychosocial symptoms than controls. Psychological factors appear to play an important role in BII and should be further investigated. Level of Evidence: 2 [ABSTRACT FROM AUTHOR]

Background: Resting-state functional connectivity (rs-FC) may aid in understanding the link between painmodulating brain regions and the descending pain modulatory system (DPMS) in fibromyalgia (FM). This study investigated whether the differences in rs-FC of the primary somatosensory cortex in responders and non-responders to the conditioned pain modulation test (CPM-test) are related to pain, sleep quality, central sensitization, and the impact of FM on quality of life. Methods: This cross-sectional study included 33 females with FM. rs-FC was assessed by functional magnetic resonance imaging. Change in the numerical pain scale during the CPM-test assessed the DPMS function. Subjects were classified either as non-responders (i.e., DPMS dysfunction, n = 13) or responders (n = 20) to CPM-test. A generalized linear model (GLM) and a receiver operating characteristic (ROC) curve analysis were performed to check the accuracy of the rs-FC to differentiate each group. Results: Non-responders showed a decreased rs-FC between the left somatosensory cortex (S1) and the periaqueductal gray (PAG) (P < 0.001). The GLM analysis revealed that the S1-PAG rs-FC in the left-brain hemisphere was positively correlated with a central sensitization symptom and negatively correlated with sleep quality and pain scores. ROC curve analysis showed that left S1-PAG rs-FC offers a sensitivity and specificity of 85% or higher (area under the curve, 0.78, 95% confidence interval, 0.63–0.94) to discriminate who does/does not respond to the CPM-test. Conclusions: These results support using the rs-FC patterns in the left S1-PAG as a marker for predicting CPM-test response, which may aid in treatment individualization in FM patients. [ABSTRACT FROM AUTHOR]

Pain is an aversive motivational state that drives an organism to escape, terminate, and avoid whatever is potentially threatening tissue health or survival, while teaching it to avoid situations associated with harm. The pain experience is distributed across a wide neural network that involves activation of the stress, autonomic, immune and opioid systems. Sustained or intense stimulation of the dynamic pain connectome results in nociplastic changes contribute to the development of persistent pain. A bidirectional relationship exists between these changes and psychosocial factors, further complicating the clinical picture. The comprehensive, wholistic approach to managing chronic pain is needed. The principles of slow medicine represent a potential theoretic framework capable of changing how the healthcare system views, manages and reimburses the management of chronic pain. The paper discusses these principles an their applicattion in the management of chronic pain. In slow medicine, the clinician is a master gardener who nurtures the patient back to optimal health rather than a mechanic who repairs damage. It seeks to replace haste, and its unintended consequences, with a calm, slow, deliberate approach to pain that benefits everyone involved in the care process. The slow medicine approach is capable of improving the management of chronic pain. [ABSTRACT FROM AUTHOR]

Pain involves both sensory and affective dimensions. The amygdala is a key player in linking nociceptive stimuli to negative emotional behaviors or affective states. Relief of pain is rewarding and activates brain reward circuits. Whether the reward circuit from the ventral tegmental area (VTA) to the central amygdala (CeA) is involved in pain relief remains unexplored. Using a model of experimental postsurgical pain, we found that pain relief elicited conditioned place preference (CPP), activated CeA-projecting dopaminergic cells in the VTA, and decreased dopaminergic D2 receptor expression in the CeA. Activation of the VTA–CeA neural pathway using optogenetic approaches relieved incisional pain. Administration of a D2 receptor agonist reversed the pain relief elicited by light-induced activation of the VTA-CeA pathway. These findings indicate that the VTA-CeA circuit is involved in pain relief in mice via dopamine receptor D2 in the CeA. [ABSTRACT FROM AUTHOR]

Background: Transcutaneous auricular vagus nerve stimulation (taVNS) stimulating the auricular branch of the vagus nerve along a well-defined neuroanatomical pathway, has promising therapeutic efficacy. Potentially, taVNS can modulate autonomic responses. Specifically, taVNS can induce more consistent parasympathetic activation and may lead to increased heart rate variability (HRV). However, the effects of taVNS on HRV remain inconclusive. Here, we investigated changes in HRV due to brief alteration periods of parasympathetic-vagal cardiac activity produced by taVNS on the cymba as opposed to control administration via the helix. Materials and Methods: We compared the effect of 10 min of active stimulation (i.e., cymba conchae) to sham stimulation (i.e., helix) on peripheral cardiovascular response, in 28 healthy young adults. HRV was estimated in the time domain and frequency domain during the overall stimulation. Results: Although active-taVNS and sham-taVNS stimulation did not differ in subjective intensity ratings, the active stimulation of the cymba led to vagally mediated HRV increases in both the time and frequency domains. Differences were significant between active-taVNS and both sham-taVNS and resting conditions in the absence of stimulation for various HRV parameters, but not for the lowfrequency index of HRV, where no differences were found between active-taVNS and sham-taVNS conditions. Conclusion: This work supports the hypothesis that taVNS reliably induces a rapid increase in HRV parameters when auricular stimulation is used to recruit fibers in the cymba compared to stimulation at another site. The results suggest that HRV can be used as a physiological indicator of autonomic tone in taVNS for research and potential therapeutic applications, in line with the established effects of invasive VNS. Knowledge of the physiological effect of taVNS short sessions in modulating cardiovagal processing is essential for enhancing its clinical use. [ABSTRACT FROM AUTHOR]

Non-invasive transcutaneous auricular vagus nerve stimulation (taVNS) as a newly developed technique involves stimulating the cutaneous receptive field formed by the auricular branch of the vagus nerve in the outer ear, with resulting activation of vagal connections to central and peripheral nervous systems. Increasing evidence indicates that maladaptive neural plasticity may underlie the pathology of several pediatric neurodevelopmental and psychiatric disorders, such as autism spectrum disorder, attention deficit hyperactivity disorder, disruptive behavioral disorder and stress-related disorder. Vagal stimulation may therefore provide a useful intervention for treating maladaptive neural plasticity. In the current review we summarize the current literature primarily on therapeutic use in adults and discuss the prospects of applying taVNS as a therapeutic intervention in specific pediatric neurodevelopmental and other psychiatric disorders. Furthermore, we also briefly discuss factors that would help optimize taVNS protocols in future clinical applications. We conclude from these initial findings that taVNS may be a promising alternative treatment for pediatric disorders which do not respond to other interventions. [ABSTRACT FROM AUTHOR]