Peripheral arterial stiffness during electrocutaneous stimulation is positively correlated with pain-related brain activity and subjective pain intensity: an fMRI study

Brain activity associated with pain perception has been revealed by numerous PET and fMRI studies over the past few decades. These findings helped to establish the concept of the pain matrix, which is the distributed brain networks that demonstrate pain-specific cortical activities. We previously found that peripheral arterial stiffness $${\beta }_{\text{art}}$$ β art responds to pain intensity, which is estimated from electrocardiography, continuous sphygmomanometer, and photo-plethysmography. However, it remains unclear whether and to what extent $${\beta }_{\text{art}}$$ β art aligns with pain matrix brain activity. In this fMRI study, 22 participants received different intensities of pain stimuli. We identified brain regions in which the blood oxygen level-dependent signal covaried with $${\beta }_{\text{art}}$$ β art using parametric modulation analysis. Among the identified brain regions, the lateral and medial prefrontal cortex and ventral and dorsal anterior cingulate cortex were consistent with the pain matrix. We found moderate correlations between the average activities in these regions and $${\beta }_{\text{art}}$$ β art (r = 0.47, p < 0.001). $${\beta }_{\text{art}}$$ β art was also significantly correlated with self-reported pain intensity (r = 0.44, p < 0.001) and applied pain intensity (r = 0.43, p < 0.001). Our results indicate that $${\beta }_{\text{art}}$$ β art is positively correlated with pain-related brain activity and subjective pain intensity. This study may thus represent a basis for adopting peripheral arterial stiffness as an objective pain evaluation metric.

Cross‐modal relationships of neural gating with the subjective perception of respiratory and somatosensory sensations

Neural gating is a phenomenon whereby the response to a stimulus recorded in the electroencephalogram (EEG) is attenuated when preceded by an identical stimulus. Such attenuation of paired auditory clicks (P50 suppression) has repeatedly been shown to be affected in multiple mental disorders, most notably schizophrenia. Neural gating has also been studied using respiratory and somatosensory sensations, however the attenuation of such bodily-relevant stimuli has not yet been systematically related to the subjective perception of bodily sensations. This research direction is potentially relevant to explaining disease trajectories in multiple psychosomatic conditions characterized by chronic breathlessness and/or pain. In the present study, we recorded high-density EEG from 85 healthy young adults while they experienced brief paired respiratory occlusions and brief paired electrocutaneous stimulation of the wrist. The event-related potential N1 at centro-lateral sites was measured in response to the second relative to the first stimulus to quantify neural gating in both sensory domains. Participants experienced resistive loaded breaths and electrocutaneous stimuli of various intensities, rated their perceived intensity and unpleasantness, and performed magnitude estimation. Both respiratory and somatosensory neural gating measures were related intra-modally and cross-modally to the subjective intensity and unpleasantness of sensations, as well as the ability to discriminate sensations of differing intensities. We report significant relationships of the somatosensory neural gating to the perceived intensity and unpleasantness of respiratory and somatosensory sensations, indicating that the stronger neural gating relates to a stronger subjective experience of intensity and unpleasantness. We discuss these unexpected findings through the lens of individual differences, as well as different theoretical accounts on the origins of cortical attenuation of repetitive stimuli.

Sensation thresholds in electrocutaneous stimulation

Acoustic or visual warning signals for workers in hazardous situations might fail under loud and/or lowvisibility work situations. A warning system should be developed that uses electrocutaneous stimulation through textile electrodes. Previous work investigated suitable stimulation parameters using TENS electrodes. The aim of this study was to compare TENS and textile cuff electrodes in terms of sensation thresholds, qualitative and spatial sensation. A study on 30 healthy volunteers (f=13, m=17) of mean age of 26.7 years was conducted applying bi-phasic rectangular current pulses to electrodes attached to the upper right arm. The study revealed that perception, attention and intolerance thresholds, qualitative and spatial perception are comparable indicating that future studies with the textile cuff electrodes can be generally based on the previous results with TENS electrodes.

Capsaicin-Induced Changes in Electrical Pain Perception Threshold Can Be Used to Assess the Magnitude of Secondary Hyperalgesia in Humans

Objectives Areas of secondary hyperalgesia can be assessed using quantitative sensory testing (QST). Delivering noxious electrocutaneous stimulation could provide added benefit by allowing multiple measurements of the magnitude of hyperalgesia. We aimed to characterize the use of electrical pain perception (EPP) thresholds alongside QST as a means by which to measure changes in pain thresholds within an area of secondary mechanical hyperalgesia. Methods EPP and heat pain thresholds (HPTs) were measured at five distinct points at baseline and following 1% capsaicin cream application, one within a central zone and four within a secondary zone. Areas of secondary mechanical hyperalgesia were mapped using QST. In a further 14 participants, capsaicin-induced reduction in EPP thresholds was mapped using a radial lines approach across 24 points. Results There was a reduction in EPP threshold measured at the four points within the secondary zone, which was within the mapped area of mechanical secondary hyperalgesia. The magnitude of secondary hyperalgesia could be split into a mild (∼4% reduction) and severe (∼21% reduction) area within an individual subject. There was no reduction in HPT within the secondary zone, but there was a reduction in both HPT and EPP threshold within the primary zone. EPP mapping revealed differences in the magnitude and spread of hyperalgesia across all subjects. Conclusions Measuring capsaicin-induced reduction in EPP thresholds can be used to map hyperalgesic areas in humans. This semi-automated approach allows rapid assessment of the magnitude of hyperalgesia, both within an individual subject and across a study population.

Electrocutaneous stimulation to the face inhibits motor evoked potentials in the hand: face-hand interactions revealed by afferent inhibition

Reorganization of the sensorimotor cortex following amputation and other interventions has revealed large-scale plastic changes between the hand and face representations. To investigate whether hand-face interactions are also present in the normal state of the system we measured sensorimotor interactions between these two areas using an afferent inhibition transcranial magnetic stimulation (TMS) protocol in which the TMS motor evoked potential (MEP) is inhibited when it is preceded by an afferent stimulus. We hypothesized that if hand-face interactions exist in the normal state of the system then stimulation of the face would inhibit hand MEPs. In two separate experiments we delivered an electrocutaneous stimulus to either the right upper lip (Experiment 1) or right cheek (Experiment 2) and recorded muscular activity from the right first dorsal interosseous (FDI). Both lip and cheek stimulation inhibited FDI MEPs. To investigate the specificity of this effect we conducted two additional experiments in which cutaneous stimulation was applied to either the right forearm (Experiment 3) or right arm (Experiment 4). Neither forearm nor arm stimulation inhibited FDI MEPs. These data provide the first evidence for face-to-hand afferent inhibition and we suggest that the mechanisms underlying these sensorimotor interactions could contribute to face/hand interactions observed following sensorimotor reorganisation.

Reorganization of Higher-Order Somatosensory Cortex After Sensory Loss from Hand in Squirrel Monkeys

Unilateral dorsal column lesions (DCL) at the cervical spinal cord deprive the hand regions of somatosensory cortex of tactile activation. However, considerable cortical reactivation occurs over weeks to months of recovery. While most studies focused on the reactivation of primary somatosensory area 3b, here, for the first time, we address how the higher-order somatosensory cortex reactivates in the same monkeys after DCL that vary across cases in completeness, post-lesion recovery times, and types of treatments. We recorded neural responses to tactile stimulation in areas 3a, 3b, 1, secondary somatosensory cortex (S2), parietal ventral (PV), and occasionally areas 2/5. Our analysis emphasized comparisons of the responsiveness, somatotopy, and receptive field size between areas 3b, 1, and S2/PV across DCL conditions and recovery times. The results indicate that the extents of the reactivation in higher-order somatosensory areas 1 and S2/PV closely reflect the reactivation in primary somatosensory cortex. Responses in higher-order areas S2 and PV can be stronger than those in area 3b, thus suggesting converging or alternative sources of inputs. The results also provide evidence that both primary and higher-order fields are effectively activated after long recovery times as well as after behavioral and electrocutaneous stimulation interventions.

Dynamics of nociceptive sensitivity in rats after melatonin treatment under normal conditions and during long-term stress exposure

Цель - изучение динамики ноцицептивной чувствительности крыс в разные временные периоды после внутрибрюшинного введения мелатонина (10 мг/кг) в условиях нормы и при однократной длительной стрессорной нагрузке на модели 24-ч иммобилизации. Результаты. Установлено, что введение мелатонина приводит к усилению перцептуального компонента ноцицепции животных, выраженность которого возрастает на протяжении 8 сут. наблюдений. На 3-и - 5-е сут. у этих особей выявлено возрастание порога вокализации в ответ на электрокожное раздражение, что иллюстрирует ослабление эмоционального компонента болевой чувствительности. Стрессорное воздействие сопровождалось снижением латентного периода реакции отведения хвоста при светотермальном раздражении, что наблюдалось сразу, а также через 1, 2 и 3 сут. после окончания стрессорного воздействия. В этих условиях увеличение порога вокализации крыс при электрокожной стимуляции обнаружено сразу после стрессорной нагрузки. Указанные изменения характеризуют усиление перцептуального компонента ноцицепции - формирование гипералгезии, но подавление эмоционального восприятия болевого раздражения на ранних стадиях постстрессорного периода. Показано, что экзогенный мелатонин не предупреждает развитие гипералгезии после 24-ч иммобилизации, однако подавляет эмоциональный компонент ноцицептивной чувствительности животных в отдаленный период после длительного стрессорного воздействия (4-е и 7-е сут.). Заключение. Применение мелатонина в целях коррекции измененной болевой чувствительности, при отрицательных эмоциогенных нагрузках, необходимо проводить с учетом временной стадии постстрессорного периода, а также принимая во внимание необходимость воздействия на перцептуальный или эмоциональный компонент ноцицепции. The dynamics of nociceptive sensitivity in rats was studied in various periods after intraperitoneal injection of melatonin (10 mg/kg) under normal conditions and during long-term stress exposure on the model of 24-h immobilization. Administration of melatonin was shown to enhance the perceptual component of nociception, whose degree progressively increased over 8 days of observations. The vocalization threshold of these specimens in response to electrocutaneous stimulation was elevated on days 3-5, which illustrates suppression of the emotional component of nociceptive sensitivity. Stress exposure in animals was accompanied by a decrease in the tail-flick latency during light-heat stimulation. It was observed immediately and 1, 2, and 3 days after termination of the stress procedure. An increase in the vocalization threshold of rats was found immediately after stress. These changes illustrate an enhancement of the perceptual component of nociception (hyperalgesia), but suppression of the emotional evaluation of pain stimulation at the early stage of the post-stress period. Exogenous melatonin did not prevent the development of hyperalgesia after 24-h restraint stress. However, melatonin inhibited the emotional component of nociceptive sensitivity in animals during the late period after long-term stress exposure (days 4 and 7). We conclude that the use of melatonin for correction of changes in nociceptive sensitivity due to negative emotiogenic factors should be performed taking into account the stage of the post-stress period and necessity to affect the perceptual or emotional component of nociception.