Heat Pain Research Articles

Nociceptive Processing of Elite Athletes Varies between Sport-Specific Loads: An EEG-Based Study Approach.

For the downstream nociceptive processing of elite athletes, recent studies indicate that athletes probably tolerate more pain as compared with a normally active population. Phenotyping the nociceptive processing of athletes in different types of endurance sports can provide insight into training-specific effects, which may help in understanding the long-term effects of specific exercise. Twenty-six elite endurance athletes from the disciplines of rowing, triathlon, and running and 26 age- and sex-matched, recreationally active control subjects who participated in the subjective pain perception and processing of standardized noxious stimuli were investigated by EEG. This included standardized heat pain thresholds (HPT) and contact heat-evoked potentials from heat stimulation, measured with EEG as well as pinprick-evoked potentials from mechanical stimulation. After noxious stimulation, athletes showed a higher activation of the event-related spectral perturbation (ERSP) patterns in the N2P2 EEG response at the Cz Electrode compared with the controls. After noxious contact heat stimulation, triathletes had a higher ERSP activation compared with the controls, whereas the rowers had a higher ERSP activation after noxious mechanical stimulation. Also, HPT in triathletes were increased despite their increased central activation after thermal stimulation. We found a correlation between increased HPT and training hours and years, although athletes did not differ within these variables. Although we were able to identify differences between athletes of different endurance sports, the reasons and implications of these differences remain unclear. The study of sport-specific somatosensory profiles may help to understand the mechanisms of exercise-related long-term effects on pain processing and perception. Furthermore, sport-specific somatosensory effects may support the personalization of exercise interventions and identify risk factors for chronic pain in elite athletes.

Low-Intensity Focused Ultrasound to the Human Dorsal Anterior Cingulate Attenuates Acute Pain Perception and Autonomic Responses.

The dorsal anterior cingulate cortex (dACC) is a critical brain area for pain and autonomic processing, making it a promising noninvasive therapeutic target. We leverage the high spatial resolution and deep focal lengths of low-intensity focused ultrasound (LIFU) to noninvasively modulate the dACC for effects on behavioral and cardiac autonomic responses using transient heat pain stimuli. A N = 16 healthy human volunteers (6 M/10 F) received transient contact heat pain during either LIFU to the dACC or Sham stimulation. Continuous electroencephalogram (EEG), electrocardiogram (ECG), and electrodermal response (EDR) were recorded. Outcome measures included pain ratings, heart rate variability, EDR response, blood pressure, and the amplitude of the contact heat-evoked potential (CHEP).LIFU reduced pain ratings by 1.09 ± 0.20 points relative to Sham. LIFU increased heart rate variability indexed by the standard deviation of normal sinus beats (SDNN), low-frequency (LF) power, and the low-frequency/high-frequency (LF/HF) ratio. There were no effects on the blood pressure or EDR. LIFU resulted in a 38.1% reduction in the P2 CHEP amplitude. Results demonstrate LIFU to the dACC reduces pain and alters autonomic responses to acute heat pain stimuli. This has implications for the causal understanding of human pain and autonomic processing in the dACC and potential future therapeutic options for pain relief and modulation of homeostatic signals.

Comparative analysis of rs-fMRI markers in heat and mechanical pain sensitivity.

This study investigates the comparative analysis of resting-state functional magnetic imaging (rs-fMRI) markers in heat and mechanical pain sensitivity among healthy adults. Using quantitative sensory testing (QST) in the orofacial area and rs-fMRI, we explored the relationship between pain sensitivities and resting-state functional connectivity (rsFC) across whole brain areas. Brain regions were spatially divided using group independent component analysis (gICA), and additional masked gICA was performed for brainstem regions. Our findings revealed that a significant number of rsFCs were correlated with either heat or mechanical pain sensitivity, with a substantial portion originating from the Sensorimotor Network (SMN). Furthermore, multivariable regression models incorporating rsFC features demonstrated predictive capabilities for pain sensitivities, with the inclusion of brainstem gICA components significantly enhancing model accuracy. Finally, a composite critical rsFC value was introduced to simplify and describe overall abnormal communication in the brain network, which could also be used in univariable regression models to predict heat and mechanical pain sensitivity.

Logistic Regression Based Model for Pain Intensity Level Detection from Biomedical Signal

Hospitals today make the effort to assess acute pain with self-report assessments such as the quantitative pain the level of intensity Index and visual input index. However, because these techniques rely on patient input, they are imprecise. Thus, an objective, statistical approach to ongoing pain monitoring is necessary. In computer vision research, identifying pain intensity is a difficult challenge to solve. However, current subjective pain evaluation is unreliable because it heavily relies on the patient's response. In order to improve the standardization of pain evaluation, automated pain identification using physiological data might provide essential objective information. In the present study, we provide an objective pain recognition approach based on physiological signals that can extract novel features from electromyography (EMG), electrodermal activity (EDA), and electrocardiogram (ECG) data that have not previously been utilized for pain recognition. Utilizing the Bio-Vid Heat Pain Database (Part A) for evaluation and clinical validation, the proposed machine learning logistic regression-based method performs significantly better than previous techniques recorded in the literature for both the electrodermal activity (EDA) and fusion approaches, with average performances of 82.36% and 83.20% for the binary classification experiment that discriminates within the baseline and the pain tolerance level (T0 vs. T4). Our result shows that it outperforms most of the previously proposed methods in related works.

Characterization of the neuropathic pain component contributing to myalgia in patients with myotonic dystrophy type 1 and 2.

Chronic muscle pain is common in myotonic dystrophies (DM). Little is known about its pathophysiology. We aimed to investigate the characteristics of the neuropathic pain component contributing contributes to the pathogenesis of chronic pain in DM. Twenty-one DM1 and 32 DM2 patients completed pain questionnaires (Brief pain inventory-BPI, PAIN-DETECT, pain disability index-PDI) and underwent neurological examination, nerve conduction studies (NCS), quantitative sensory testing (QST, dorsum of the right hand and right thigh) and skin biopsy to determine the intraepidermal nerve fiber density (IENFD, distal and proximal site of lower extremity). NCS and QST results at the thigh were compared to 27 healthy controls and IENFD and QST at the dorsum of the hand to published reference values. The sensory profile of DM2 patients was characterized by a loss in thermal and mechanical detection, while DM1 patients showed reduced mechanical and heat pain thresholds and higher mechanical pain sensitivity. Both DM groups showed pressure hyperalgesia. IENFD was reduced in 63% of DM1 patients and 50% of DM2. The slightly higher pain interference and disability found in DM2 was rather due to age difference than disease. Similar pain mechanisms likely occur in both DM1 and DM2, even though a tendency toward more pain sensitivity was observed in DM1 and more sensory loss in DM2. Both QST and reduced IENFD highlight the presence of peripheral nerve damage in DM. This must be considered for the best pain management strategies.

Reliability and minimal detectable change of dynamic temporal summation and conditioned pain modulation using a single experimental paradigm.

Quantitative sensory tests (QST) are frequently used to explore alterations in somatosensory systems. Static and dynamic QST like pain threshold and temporal summation (TS) and conditioned pain modulation (CPM) are commonly used to evaluate excitatory and inhibitory mechanisms involved in pain processing. The aim of the present study was to document the reliability and the minimal detectable change (MDC) of these dynamic QST measurements using a standardized experimental paradigm. Forty-six (46) pain-free participants took part in 2 identical sessions to collect TS and CPM outcomes. Mechanical (pressure pain threshold [PPT]) and thermal (constant 2-minute heat pain stimulation [HPS]) nociceptive stimuli were applied as test stimuli, before and after a cold-water bath (conditioning stimulus). TS was interpreted as the change in pain perception scores during HPS. CPM were determined by calculating the difference in pain perception between pre- and post- water bath for both PPT and HPS. Relative and absolute reliability were analyzed with intra-class correlation coefficient (ICC2, k), standard error of the measurements (SEMeas) and MDC. Results revealed a good to excellent relative reliability for static QST (ICC ≥ 0.73). For TS, a poor to moderate relative reliability depending on the calculation methods (ICC = 0.25 ≤ ICC ≤ 0.59), and a poor relative reliability for CPM (ICC = 0.16 ≤ ICC ≤ 0.37), both when measured with mechanical stimulation (PPT) and thermal stimulation (HPS). Absolute reliability varied from 0.73 to 7.74 for static QST, 11 to 22 points for TS and corresponded to 11.42 points and 1.56 points for thermal and mechanical-induced CPM, respectively. MDC analyses revealed that a change of 1.58 to 21.46 point for static QST, 31 to 52 points for TS and 4 to 31 points for CPM is necessary to be interpreted as a real change. Our approach seems well-suited to clinical use. Although our method shows equivalent relative and absolute reliability compared to other protocols, we found that the reliability of endogenous pain modulation mechanisms is vulnerable, probably due to its dynamic nature.

Association between myofascial trigger point therapy and conditioned pain modulation

IntroductionMyofascial trigger point therapy (MTrP) is a widely used therapeutic approach, although the underlying mechanisms remain unclear. Mechanisms discussed include peripheral involvement of muscles as well as central pain modulating processes such as the conditioned pain modulation (CPM). The aim of this study was to investigate whether the analgesic response of MTrP and the analgesic response of CPM correlate in asymptomatic participants in order to identify shared underlying mechanisms of MTrP and CPM. MethodBoth, CPM and MTrP protocols consisted of heat-based test stimuli (heat pain thresholds before and after the intervention) and pressure-based (conditioning) stimuli. Asymptomatic participants (n = 94) were randomly assigned to receive either mild, intense or no pressure stimuli (between-group design) to both the fingernail and the MTrP of the infraspinatus muscle (within-group design). Pressure stimuli at both locations (fingernail, MTrP) were applied with a pressure algometer for 120 s and continuously adjusted to maintain a constant pain intensity of mild or intense pain. All thermal stimuli were applied on the lower leg with a thermal stimulator. ResultsA significant correlation was shown between the analgesic effect of CPM and MTrP therapy for mild (r = 0.53, p = 0.002) and intensive stimuli (r = 0.73, p < 0.001). 17.3% of the variance of the MTrP effect were explained by CPM after mild stimulation, and 47.1% after intense stimulation. Pain-related characteristics did not explain the variance within the analgesic response using a regression analysis. ConclusionsBetween the analgesic responses following MTrP and CPM paradigms, a moderate to strong correlation was observed, suggesting shared underlying mechanisms.

Transcranial Direct Current Stimulation (tDCS) Effects on Quantitative Sensory Testing (QST) and Nociceptive Processing in Healthy Subjects: A Systematic Review and Meta-Analysis.

The aim of this study is to determine the effect that different tDCS protocols have on pain processing in healthy people, assessed using quantitative sensory tests (QST) and evoked pain intensity. We systematically searched in EMBASE, CINAHL, PubMed, PEDro, PsycInfo, and Web of Science. Articles on tDCS on a healthy population and regarding QST, such as pressure pain thresholds (PPT), heat pain thresholds (HPT), cold pain threshold (CPT), or evoked pain intensity were selected. Quality was analyzed using the Cochrane Risk of Bias Tool and PEDro scale. Twenty-six RCTs were included in the qualitative analysis and sixteen in the meta-analysis. There were no significant differences in PPTs between tDCS and sham, but differences were observed when applying tDCS over S1 in PPTs compared to sham. Significant differences in CPTs were observed between tDCS and sham over DLPFC and differences in pain intensity were observed between tDCS and sham over M1. Non-significant effects were found for the effects of tDCS on HPTs. tDCS anodic over S1 stimulation increases PPTs, while a-tDCS over DLPFC affects CPTs. The HPTs with tDCS are worse. Finally, M1 a-tDCS seems to reduce evoked pain intensity in healthy subjects.

DIFFERENTIAL PAIN SENSATION AND GUT MICROBIOME BETWEEN YOUNG AND OLDER ADULTS

Abstract This study aimed to investigate the differences in pain sensation and gut microbiota between young and older adults. Twenty-one healthy young adults (YAs) and sixteen healthy older adults (OAs) were recruited. Quantitative sensory testing data, and stool samples were collected. The 16S rRNA V4 gene region of stool samples were sequenced and processed by using the Mothur 1.42.3 pipeline. The mean ages of YAs and OAs were 20.14 (SD = 1.39) and 63.19 (SD = 8.00), respectively. Eleven of the YAs and 12 of the OAs were female, and 8 of the YAs and 3 of the OAs reported pain. OAs had significantly higher heat pain threshold (HPT), higher pressure pain threshold (PPT), lower cold detection threshold (CDT), and lower cold pain threshold (CPT) than YAs (all p &amp;lt; 0.05). OAs had significantly different a-diversity indices including higher species of observed (Sobs), Chao index and Shannon index, and lower coverage, and significantly different beta diversity indices (Bray-Curtis, Jaccard, and Theta YC) than YAs. The significantly abundant taxa in YAs included Bacteroidaceae, Veillonellaceae, and Alcaligenaceae. Coriobacteriaceae, Streptococcaceae, Lachnospiraceae, Erysipelotrichaceae, and Verrucomicrobiaceae were significantly enriched in OAs. The Spearman correlation analysis showed that the CDT, CPT, and HPT were significantly associated with gut microbiota Sobs, Chao index, Shannon index, and coverage (all p &amp;lt; 0.05). But the directions and coefficients of correlations varied. OAs had distinguished peripheral sensation and gut microbiota profiles than YAs. The changed peripheral sensation and gut microbiota profiles among OAs may be biomarkers of aging-related pain processing.

Biopsychosocial contributors to irritability in individuals with shoulder or low back pain

ABSTRACT Objectives Irritability is a foundational clinical reasoning concept in rehabilitation to evaluate reactivity of the examination and treatment. While originally theorized to reflect tissue damage, a large body of evidence supports pain is a biopsychosocial experience impacted by pain sensitivity and psychological factors. Therefore, the purpose of this study was to examine biopsychosocial contributors to irritability. Methods 40 patients with shoulder (n = 20) and low back (n = 20) pain underwent Quantitative Sensory Testing (QST) (Pressure Pain Threshold, Heat Pain Threshold, Conditioned Pain Modulation, Temporal Summation), completed pain-related psychological questionnaires, an Exercise-Induced Hypoalgesia protocol, and standardized irritability assessment based on Clinical Practice Guidelines. Participants were then categorized as irritable or not irritable based on Maitland’s criteria and by irritability level based on Clinical Practice Guidelines. An independent samples t-test examined for differences in QST and psychological factors by irritability category. A MANOVA examined for differences in QST and psychological factors by irritability level (high, moderate, low). Results Significantly lower heat and pressure pain thresholds at multiple locations (p < 0.05), as well as less efficient conditioned pain modulation (p = 0.02), were demonstrated in individuals categorized as irritable. Heat and pressure pain thresholds were also significantly lower in patients with high irritability compared to other levels. Significantly higher depression and anger, as well as lower self-efficacy, were reported in individuals with an irritable presentation. Discussion/Conclusion Biopsychosocial factors, including widespread hyperalgesia and elevated psychological factors, may contribute to an irritable presentation.

Social support of virtual characters reduces pain perception.

Psychosocial factors, such as social support, can reduce pain. Virtual reality (VR) is a powerful tool to decrease pain, but social factors in VR-based pain analgesia have rarely been studied. Specifically, it is unclear whether social support by virtual characters can reduce pain and whether the perceived control behind virtual characters (agency) and varying degrees of social cues impact pain perception. Healthy participants (N = 97) received heat pain stimulation while undergoing four within-subject conditions in immersive VR: (1) virtual character with a low number of social cues (virtual figure) provided verbal support, (2) virtual character with a high number of social cues (virtual human) provided verbal support, (3) no social support (hearing neutral words), (4) no social support. Perceived agency of the virtual characters served as between-subjects factor. Participants in the avatar group were led to believe that another participant controlled the virtual characters. Participants in the agent group were told they interacted with a computer. However, in both conditions, virtual characters were computer-controlled. Pain ratings, psychophysiological measurements and presence ratings were recorded. Virtual social support decreased pain intensity and pain unpleasantness ratings but had no impact on electrodermal activity nor heart rate. A virtual character with a high number of social cues led to lower pain unpleasantness and higher feelings of presence. Agency had no significant impact. Virtual characters providing social support can reduce pain independent of perceived agency. A more human visual appearance can have beneficial effects on social pain modulation by virtual characters. Social influences are important factors in pain modulation. The current study demonstrated analgesic effects through verbal support provided by virtual characters and investigated modulating factors. A more human appearance of a virtual character resulted in a higher reduction of pain unpleasantness. Importantly, agency of the virtual characters had no impact. Given the increasing use of digital health interventions, the findings suggest a positive impact of virtual characters for digital pain treatments.

A Comprehensive Study on Pain Assessment from Multimodal Sensor Data.

Pain assessment is a critical aspect of healthcare, influencing timely interventions and patient well-being. Traditional pain evaluation methods often rely on subjective patient reports, leading to inaccuracies and disparities in treatment, especially for patients who present difficulties to communicate due to cognitive impairments. Our contributions are three-fold. Firstly, we analyze the correlations of the data extracted from biomedical sensors. Then, we use state-of-the-art computer vision techniques to analyze videos focusing on the facial expressions of the patients, both per-frame and using the temporal context. We compare them and provide a baseline for pain assessment methods using two popular benchmarks: UNBC-McMaster Shoulder Pain Expression Archive Database and BioVid Heat Pain Database. We achieved an accuracy of over 96% and over 94% for the F1 Score, recall and precision metrics in pain estimation using single frames with the UNBC-McMaster dataset, employing state-of-the-art computer vision techniques such as Transformer-based architectures for vision tasks. In addition, from the conclusions drawn from the study, future lines of work in this area are discussed.

Transformer encoder with multiscale deep learning for pain classification using physiological signals.

Pain, a pervasive global health concern, affects a large segment of population worldwide. Accurate pain assessment remains a challenge due to the limitations of conventional self-report scales, which often yield inconsistent results and are susceptible to bias. Recognizing this gap, our study introduces PainAttnNet, a novel deep-learning model designed for precise pain intensity classification using physiological signals. We investigate whether PainAttnNet would outperform existing models in capturing temporal dependencies. The model integrates multiscale convolutional networks, squeeze-and-excitation residual networks, and a transformer encoder block. This integration is pivotal for extracting robust features across multiple time windows, emphasizing feature interdependencies, and enhancing temporal dependency analysis. Evaluation of PainAttnNet on the BioVid heat pain dataset confirm the model's superior performance over the existing models. The results establish PainAttnNet as a promising tool for automating and refining pain assessments. Our research not only introduces a novel computational approach but also sets the stage for more individualized and accurate pain assessment and management in the future.

Translation, cross-cultural adaptation and measurement proprieties of the German version of the Allodynia Symptom Checklist (ASC-12)

BackgroundCutaneous allodynia is highly prevalent among migraineurs and is associated with a poor prognosis. The Allodynia Symptom Checklist (ASC-12) is a comprehensive questionnaire to identify the presence and severity of allodynia. Our aim was to translate and adapt the ASC-12 to German and evaluate its measurement properties.MethodsFollowing the COSMIN guidelines, 80 migraine patients were enrolled in the study to evaluate the stages of translation (n=30) and measurement propriety assessment (n=50), respectively. After reaching a final version, the German ASC-12 was assessed for structural validity, internal consistency, test-retest reliability, construct validity and absolute agreement, using mechanical and thermal pain thresholds as reference method.ResultsThe German version of the ASC-12 presented an adequate structural validity compatible with the original version of the questionnaire. Its internal consistency ranged from 0.70 to 0.80 considering the total score and the thermic, static and dynamic mechanic subdomains. The total score presented excellent reliability (ICC: 0.85) with a standard error of measurement of 1.15 points and smallest detectable change of 3.40 points. ASC-12 total scores were correlated with headache intensity (r=0.38, p=0.004), headache disability (r=0.37, p=0.004) and cold pain thresholds (r=0.28, p=0.025). The thermic allodynia ASC-12 scores were correlated with cold (r=0.36, p=0.005) and heat (r=-0.30, p=0.010) pain thresholds, while the static mechanical allodynia ASC-12 scores correlated with mechanical pain threshold (r=0.29, p=0.019) and with mechanical pain sensitivity (r=0.24 to 0.28, p< 0.045). Despite no significant bias between methods, quantitative sensory testing (QST) results and ASC-12 scores tend to disagree.ConclusionThe German version of the ASC-12 is available for research and clinical settings and presented adequate measurement proprieties, as the original version. Despite the correlation between the ASC-12 and QST, one method cannot be replaced by the other.

Constraints Affecting the Welfare of Domestic Sheep Grazing in the Natural Pasture

The sheep like other animals need more and more welfare to produce meat of good quality, Sheep welfare problems primarily arise from mutilations, lameness, transportation, and disease. With proper grazing, breeding, and husbandry practices, most health issues in sheep can be resolved or avoided. Grazing involves seeking and choosing feed as well as grabbing and consuming it. The manner in which ruminants or grazing animals grip and consume forages varies. These variations are connected to the sorts of fodder that various ruminants prefer. Heat stress, cold stress, weariness, prolonged thirst, prolonged hunger, hampered movement, movement restrictions, resting issues, social stress, pain, fear, and distress are the welfare types that sheep may encounter during caged, all issues due to shortage of welfare, this results in sheep inside the body that acts as a substance that cannot be used in the metabolic processes and is difficult to get rid of the animal is able to get rid of these substances accumulated inside the body that are difficult to get rid of the presence of natural toxins can be produced through the accumulation of some chemical substances and elements that the animal gets from the food. They come as residues from deteriorated cells or some vital processes in the body.

Physical activity, sitting time, and thermal quantitative sensory testing responses in African Americans.

Prior research suggests that African Americans (AAs) have more frequent, intense, and debilitating pain and functional disability compared with non-Hispanic Whites (NHWs). Potential contributing factors to this disparity are physical activity and sedentary behavior, given that AAs are less physically active, and physical activity is associated with antinociception (whereas sedentary behavior is linked to pronociception). However, impact of these factors on pain processing has largely been unexplored in AAs, especially before chronic pain onset. This study examined relationships between physical activity, sedentary behavior (sitting time), and laboratory measures of pain and pain modulation in adult AAs. These included heat pain threshold and tolerance, temporal summation of pain (TSP, a marker of central sensitization), and conditioned pain modulation (CPM, a marker of descending pain inhibition). Multiple regressions were conducted to examine the effects of physical activity and sitting time on heat threshold and tolerance. Multilevel models were conducted to assess the relationship between physical activity, sitting time, and temporal summation of pain. Additional multilevel models were conducted to assess the relationship between physical activity, sitting time, and conditioned pain modulation. Higher level of physical activity, but not sitting time, was associated with reduced TSP slopes. Neither physical activity nor sitting time was associated with CPM slopes. No significant relationships between physical activity or sitting time and heat pain threshold or tolerance were detected. These findings suggest that physical activity is associated with reduced TSP, an effect which may be driven by reduced spinal hyperexcitability in more active individuals. Thus, structural and individual interventions designed to increase physical activity in healthy, young AAs may be able to promote antinociceptive processes (ie, reduced TSP/reduced pain facilitation) potentially protective against chronic pain.

Effect of spinal cord stimulation for thermal noxious stimulus pain threshold in Parkinson's disease

BackgroundParkinson's disease (PD)-related pain or PD pain is a frequent non-motor symptom and is treated with pharmacotherapy and non-pharmacologic therapies such as deep brain stimulation (DBS) and spinal cord stimulation (SCS). The mechanism of PD pain relief by DBS is thought to involve increased pain threshold to nociceptive stimulation, whereas the mechanism of SCS has not been elucidated. ObjectivePD pain relief by SCS may involve modulation of the pain thresholds in the spinal cord segments and supra-spinal actions. Therefore, we investigated the effect of SCS in patients who underwent SCS for intractable PD pain in the lower extremities by measuring pain thresholds to thermal nociceptive stimulation of the lower (leg) and upper (hand) parts of the stimulated spinal segment during SCS-off and SCS-on using quantitative sensory testing to determine the pain threshold. MethodsSeven PD patients with SCS in the lower thoracic spinal cord underwent measurements of cold sensory threshold, warm sensory threshold, cold pain threshold (CPT), and heat pain threshold (HPT). ResultsIn upper part of the stimulated spinal segment, CPT was significantly decreased during SCS-on compared to SCS-off (p < 0.01); whereas HPT was not significantly different. In lower part of the stimulated spinal segment, CPT was significantly increased during SCS-on compared to SCS-off (p < 0.05); and HPT was also increased (p < 0.05). ConclusionThis study shows that SCS raises the pain threshold to thermal nociception in PD patients. The primary mechanism of pain relief by SCS is thought to be segmental inhibition at the level of the stimulated spinal segments.

The Effect of Glycine and N-Acetylcysteine on Oxidative Stress in the Spinal Cord and Skeletal Muscle After Spinal Cord Injury

Oxidative stress is a frequently occurring pathophysiological feature of spinal cord injury (SCI) and can result in secondary injury to the spinal cord and skeletal muscle atrophy. Studies have reported that glycine and N-acetylcysteine (GlyNAC) have anti-aging and anti-oxidative stress properties; however, to date, no study has assessed the effect of GlyNAC in the treatment of SCI. In the present work, we established a rat model of SCI and then administered GlyNAC to the animals by gavage at a dose of 200 mg/kg for four consecutive weeks. The BBB scores of the rats were significantly elevated from the first to the eighth week after GlyNAC intervention, suggesting that GlyNAC promoted the recovery of motor function; it also promoted the significant recovery of body weight of the rats. Meanwhile, the 4-week heat pain results also suggested that GlyNAC intervention could promote the recovery of sensory function in rats to some extent. Additionally, after 4 weeks, the levels of glutathione and superoxide dismutase in spinal cord tissues were significantly elevated, whereas that of malondialdehyde was significantly decreased in GlyNAC-treated animals. The gastrocnemius wet weight ratio and total antioxidant capacity were also significantly increased. After 8 weeks, the malondialdehyde level had decreased significantly in spinal cord tissue, while reactive oxygen species accumulation in skeletal muscle had decreased. These findings suggested that GlyNAC can protect spinal cord tissue, delay skeletal muscle atrophy, and promote functional recovery in rats after SCI.

Repetitive Transcranial Magnetic Stimulation of the Human Motor Cortex Modulates Processing of Heat Pain Sensation as Assessed by the Offset Analgesia Paradigm.

Offset analgesia (OA), which is defined as a disproportionately large reduction in pain perception following a small decrease in a heat stimulus, quantifies temporal aspects of endogenous pain modulation. In this study on healthy subjects, we aimed to (i) determine the Heat Pain Threshold (HPT) and the response to constant and dynamic heat stimuli assessing sensitization, adaptation and OA phenomena at the thenar eminence; (ii) evaluate the effects of high-frequency repetitive Transcranial Magnetic Stimulation (rTMS) of the primary motor cortex (M1) on these measures. Twenty-four healthy subjects underwent quantitative sensory testing before and after active or sham 10 Hz rTMS (1200 stimuli) of the left M1, during separate sessions. We did not observe any rTMS-related changes in the HPT or visual analogue scale (VAS) values recorded during the constant trial. Of note, at baseline, we did not find OA at the thenar eminence. Only after active rTMS did we detect significantly reduced VAS values during dynamic heat stimuli, indicating a delayed and attenuated OA phenomenon. rTMS of the left M1 may activate remote brain areas that belong to the descending pain modulatory and reward systems involved in the OA phenomenon. Our findings provide insights into the mechanisms by which rTMS of M1 could exert its analgesic effects.

Gender Differences in Pain Threshold, Unpleasantness, and Descending Pain Modulatory Activation Across the Adult Life Span: A Cross Sectional Study

The neurobiological underpinnings of gender differences in pain perception, and how these differences may be modified by age, are incompletely understood, placing patients at risk of suboptimal pain management. Using functional magnetic resonance imaging, we examined brain responses in the descending pain modulatory system (DPMS, specifically, dorsolateral prefrontal cortex, anterior cingulate cortex, insula, hypothalamus, amygdala, and periaqueductal gray, during an evoked pain task. We investigated the interaction of age and gender in our sample of healthy adults (27 females, 32 males, 30–86 years) on DPMS response. In a perceptually matched thermal pain paradigm, we investigated pain unpleasantness and neural responses for 3 heat pain percepts: just noticeable pain, weak pain, and moderate pain (MP). Females reported just noticeable pain at a lower temperature, but reported less unpleasantness at weak pain and MP percepts, compared to males. There was a significant age-by-gender interaction during moderate pain in the right anterior cingulate cortex and bilateral insula, such that, males had a stronger positive relationship between DPMS response and age compared to females in these regions. Our results indicate that differences in DPMS responses may explain some gender differences in pain perception and that this effect may change across the adult lifespan. PerspectiveGender differences in pain have been well-documented but the brain mechanisms for these differences are still unclear. This article describes potential differences in brain functioning during different levels of pain that could explain differences in pain responses between men and women across the adult lifespan.