Skin Stimuli Research Articles

Slow depolarizing electrical stimuli reveal differential time courses of nociceptor recovery after prolonged topical capsaicin in human skin

AbstractBackgroundWe examined de‐functionalization and temporal functional recovery of C‐nociceptor evoked pain after topical 8% capsaicin applied for 4 consecutive days.MethodsCapsaicin and placebo patches were applied to human forearm skin (n = 14). Cold, warmth and heat pain thresholds, pain NRS to electrical and thermal (48°C, 5 s) stimuli and axon reflex flare were recorded weekly for 49 days. Mechanical and heat sensitive (‘polymodal’) nociceptors were activated by single electrical half‐period sinusoidal pulses (0.5 s, 1 Hz). Mechanical and heat insensitive (‘silent’) nociceptors were activated by 4 Hz sinusoidal stimuli.ResultsCapsaicin abolished heat pain. Sensation to electrical sinusoidal stimulation was reduced but never abolished during the treatment. Pain to electrical 1 Hz ‘polymodal’ nociceptor stimulation took longer to recover than pain ratings to 4 Hz 2.5 s sinusoidal stimulation activating ‘polymodal’ and ‘silent’ nociceptors (35 vs. 21 days). Heat pain was indifferent to placebo from day 21–49. Axon reflex flare was abolished during capsaicin and only recovered to ~50% even after 49 days.ConclusionsCapsaicin abolishes heat transduction at terminal nociceptive endings, whereas small‐diameter axons sensitive to sinusoidal electrical stimulation can still be activated. 1 Hz depolarizing stimuli evoke burst discharges, as demonstrated before, and recover slower after capsaicin than single pulses induced by 4 Hz. The difference in recovery suggests differential time course of functional regeneration for C‐nociceptor sub‐types after capsaicin. All sensations recovered completely within 7 weeks in healthy subjects. Our findings contrast analgesia lasting for months in spontaneous neuropathic pain patients treated with 8% capsaicin.SignificanceSinusoidal electrical stimulation can still activate small diameter axons desensitized to heat after 4 consecutive days of topical 8% capsaicin application and reveals differential temporal functional regeneration of C‐nociceptor sub‐types. Electrical sinusoidal stimulation may detect such axons that no longer respond to heat stimuli in neuropathic skin.

Surprising multifunctionality of a Tritonia swim CPG neuron: C2 drives the early phase of postswim crawling despite being silent during the behavior.

In response to a suitably aversive skin stimulus, the marine mollusk Tritonia diomedea launches an escape swim followed by several minutes of high-speed crawling. The two escape behaviors are highly dissimilar: whereas the swim is a muscular behavior involving alternating ventral and dorsal whole body flexions, the crawl is a nonrhythmic gliding behavior mediated by the beating of foot cilia. The serotonergic dorsal swim interneurons (DSIs) are members of the swim central pattern generator (CPG) and also strongly drive crawling. Although the swim network is very well understood, the Tritonia crawling network to date comprises only three neurons: the DSIs and pedal neurons 5 and 21 (Pd5 and Pd21). Since Tritonia's swim network has been suggested to have arisen from a preexisting crawling network, we examined the possible role that another swim CPG neuron, C2, may play in crawling. Because of its complete silence in the postswim crawling period, C2 had not previously been considered to play a role in driving crawling. However, semi-intact preparation experiments demonstrated that a brief C2 spike train surprisingly and strongly drives the foot cilia for ∼30 s, something that cannot be explained by its synaptic connections to Pd5 and Pd21. Voltage-sensitive dye (VSD) imaging in the pedal ganglion identified many candidate crawling motor neurons that fire at an elevated rate after the swim and also revealed several pedal neurons that are strongly excited by C2. It is intriguing that unlike the DSIs, which fire tonically after the swim to drive crawling, C2 does so despite its postswim silence.NEW & NOTEWORTHY Tritonia swim central pattern generator (CPG) neuron C2 surprisingly and strongly drives the early phase of postswim crawling despite being silent during this period. In decades of research, C2 had not been suspected of driving crawling because of its complete silence after the swim. Voltage-sensitive dye imaging revealed that the Tritonia crawling motor network may be much larger than previously known and also revealed that many candidate crawling neurons are excited by C2.

Relief of post-stroke spasticity with acute vibrotactile stimulation: controlled crossover study of muscle and skin stimulus methods.

Prior work suggests that vibratory stimulation can reduce spasticity and hypertonia. It is unknown which of three predominant approaches (stimulation of the spastic muscle, antagonist muscle, or cutaneous regions) most reduces these symptoms. Determine which vibrotactile stimulation approach is most effective at reducing spastic hypertonia among post-stroke patients. Sham-controlled crossover study with random assignment of condition order in fourteen patients with post-stroke hand spasticity. All patients were studied in four conditions over four visits: three stimulation conditions and a sham control. The primary outcome measure was the Modified Ashworth Scale, and the secondary outcome measure was the Modified Tardieu Scale measured manually and using 3D motion capture. For each condition, measures of spastic hypertonia were taken at four time points: baseline, during stimulation, after stimulation was removed, and after a gripping exercise. A clinically meaningful difference in spastic hypertonia was found during and after cutaneous stimulation of the hand. Modified Ashworth and Modified Tardieu scores were reduced by a median of 1.1 (SD = 0.84, p = 0.001) and 0.75 (SD = 0.65, p = 0.003), respectively, during cutaneous stimulation, and by 1.25 (SD = 0.94, p = 0.001) and 0.71 (SD = 0.67, p = 0.003), respectively, at 15 min after cutaneous stimulation. Symptom reductions with spastic muscle stimulation and antagonist muscle stimulation were non-zero but not significant. There was no change with sham stimulation. Cutaneous vibrotactile stimulation of the hand provides significant reductions in spastic hypertonia, compared to muscle stimulation. www.ClinicalTrials.gov, identifier: NCT03814889.

Flexible integrated sensor with asymmetric structure for simultaneously 3D tactile and thermal sensing

The human body detects tactile stimuli through a combination of pressure force and temperature signals via various cutaneous receptors. The development of a multifunctional artificial tactile perception system has potential benefits for future robotic technologies, human-machine interfaces, artificial intelligence, and health monitoring devices. However, constructing systems beyond simple pressure sensing capabilities remains challenging. Here, we propose an artificial flexible and ultra-thin (50 μ m) skin system to simultaneously capture 3D tactile and thermal signals, which mimics the human tactile recognition process using customized sensor pairs and compact peripheral signal-converting circuits. The 3D tactile sensors have a flower-like asymmetric structure with 5-ports and 4 capacitive elements in pairs. Differential and average signals would reveal the curl and amplitude values of the fore field with a resolution of 0.18/mm. The resistive thermal sensors are fabricated with serpentine lines and possess stable heat-sensing performance (165 mV/°C) under shape deformation conditions. Real-time monitoring of the skin stimuli is displayed on the user interface and stored on mobile clients. This work offers broad capabilities relevant to practical applications ranging from assistant prosthetics to artificial electronic skins.

Online Pressure Map Reconstruction in a Multitouch Soft Optical Waveguide Skin

In this article, we present a reconstruction method for mapping a wide range of pressure stimuli in a multitouch soft optical waveguide skin (MSOWS). Distributed sensing information is typically obtained from wired soft sensing units. This approach hardly adapts to different shapes and has limited durability against stresses and shocks. In our MSOWS, the spatial tactile transduction relies on a continuum sensitive area of graded-stiffness polydimethylsiloxane, with a virtual grid free from electronics and connections. The sensing range of each cell is up to 234 kPa, and the spatial resolution is 5 mm. We use a time-delay neural network to reduce the hysteresis of the soft material to less than 1%. In addition, a fault-tolerant mechanism makes the entire system robust to component failure. These results may open the way to a new generation of distributed soft skins that are versatile due to material design and processing.

Perceived Intensities of Normal and Shear Skin Stimuli Using a Wearable Haptic Bracelet

Our aim is to provide effective interaction with virtual objects, despite the lack of co-location of virtual and real-world contacts, while taking advantage of relatively large skin area and ease of mounting on the forearm. We performed two human participant studies to determine the effects of haptic feedback in the normal and shear directions during virtual manipulation using haptic devices worn near the wrist. In the first study, participants performed significantly better while discriminating stiffness values of virtual objects when the feedback consisted of normal displacements compared to shear displacements. Participants also commented that they could detect normal cues much easier than shear, which motivated us to perform a second study to find the point of subjective equality (PSE) between normal and shear stimuli. Our results show that shear stimuli require a larger actuator displacement but less force than normal stimuli to achieve perceptual equality for our haptic bracelets. We found that normal and shear stimuli cannot be equalized through skin displacement nor the interaction forces across all users. Rather, a calibration method is needed to find the point of equality for each user where normal and shear stimuli create the same intensity on the user's skin.

Analysis of Dipolar Sources in the Solution of the Electroencephalographic Inverse Problem

In this work, we propose a solution to the problem of identification of sources in the brain from measurements of the electrical potential, recorded on the scalp EEG (electroencephalogram), where boundary problems are used to model the skull, brain region, and scalp, solving the inverse problem from the EEG measurements, the so-called Electroencephalographic Inverse Problem (EIP), which is ill-posed in the Hadamard sense since the problem has numerical instability. We focus on the identification of volumetric dipolar sources of the EEG by constructing and modeling a simplification to reduce the multilayer conductive medium (two layers or regions Ω1 and Ω2) to a problem of a single layer of a homogeneous medium with a null Neumann condition on the boundary. For this simplification purpose, we consider the Cauchy problem to be solved at each time. We compare the results we obtained solving the multiple layers problem with those obtained by our simplification proposal. In both cases, we solve the direct and inverse problems for two different sources, as synthetic results for dipolar sources resembling epileptic foci, and a similar case with an external stimulus (intense light, skin stimuli, sleep problems, etc). For the inverse problem, we use the Tikhonov regularization method to handle its numerical instability. Additionally, we build an algorithm to solve both models (multiple layers problem and our simplification) in time, showing optimization of the problem when considering 128 divisions in the time interval [0,1] s, solving the inverse problem at each time (interval division) and comparing the recovered source with the initial one in the algorithm. We observed a significant decrease in the computation times when simplifying the numerical calculations, resulting in a decrease up to 50% in the execution times, between the EIP multilayer model and our simplification proposal, to a single layer homogeneous problem of a homogeneous medium, which translates into a numerical efficiency in this type of problem.

Evaluating the role of Approach-Avoidance Training on action-tendencies in individuals with skin-picking disorder: A preliminary randomized experiment.

Background and aimsPathological skin-picking (PSP) or excoriation disorder is a destructive behavior that affects 1-2% of the general population. The purpose of this pilot study was to evaluate the effect of a computerized behavior modification task on action-tendencies (i.e., approach or avoidance) in adults with PSP. We aimed to modify these action-tendencies by having participants with PSP complete the Approach-Avoidance Training (AAT) task, using a joystick to simulate an approach (=pull) or avoidance (=push) response.MethodForty-five participants diagnosed with PSP were randomized to one of three training conditions: (1) Avoidance Training (AvT; n = 15), (2) Approach Training (ApT; n = 15), or (3) Placebo Training (PT; n = 15). We hypothesized that after training, those in the AvT would have the greatest reduction in behavioral approach (i.e., their overall reaction time [RT] to approach pictures of irregular skin stimuli).ResultsResults of the pre-training assessment task revealed a positive correlation between behavioral approach to irregular skin stimuli and skin-picking severity as assessed by the Skin Picking Scale-Revised (SPS-R). After training, a lower behavioral approach and urges to pick were found in the AvT and PT groups, while those in the ApT reported higher behavioral approach and urges to pick. At two-week follow-up, no significant changes on the SPS-R were reported between groups.DiscussionOur preliminary data suggest that the AAT is a promising avenue of research to develop as a cognitive intervention to address an excessive behavioral approach tendency that characterizes skin-picking problems.

The effect of light massage on blood pressure and mean arterial pressure in tuberculosis patients

Tuberculosis is still a significant problem in the health sector, including the side effects of its treatment. Side effects include indigestion, nausea, joint pain, dizziness, reddish urine, itching, redness of the skin, liver disorders, joint pain, and vascular disorders such as paresthesia and even hypertension. Light massage is a massage therapy in the form of gentle movements on the soft tissues of the body, including rubbing and rubbing movements. This skin stimulus will provide a sense of comfort, relax tension in muscles and improve blood circulation. This study aimed to determine the effect of light massage therapy on blood pressure and mean atrial pressure (MAP) in tuberculosis patients. This study used a experimental design, pre-post control group design. The sample size of this study was 60 respondents. The sampling technique used was simple random. The results showed that most respondents were female (56.7%) with active phase treatment 76.7% in the intervention group and 73.4% in the control group. There was a significant difference in systolic blood pressure and MAP (p <0.05), and there was no significant difference in diastolic blood pressure between the intervention and control groups (p> 0.05). Light massage can reduce systolic blood pressure and MAP. Further research is needed to increase the duration and frequency of light massage interventions

PVC-SLP: Perceptual Vibrotactile-Signal Compression Based-on Sparse Linear Prediction

Developing a signal compression technique that is able to achieve a low bit rate while maintaining high perceptual signal quality is a classical signal processing problem vigorously studied for audio, speech, image, and video type of signals. Yet, until recently, there has been limited effort directed toward the compression of vibrotactile signals, which represent a crucial element of rich touch (haptic) information. A vibrotactile signal; produced when stroking a textured surface with a tool-tip or bare-finger; like other signals contains a great deal of redundant and imperceptible information that can be exploited for efficient compression. This paper presents PVC-SLP, a vibrotactile perceptual coding approach. PVC-SLP employs a model of tactile sensitivity; called ASF (Acceleration Sensitivity Function); for perceptual coding. The ASF is inspired by the four channels model that mediate the perception of vibrotactile stimuli in the glabrous skin. The compression algorithm introduces sparsity constraints in a linear prediction scheme both on the residual and the predictor coefficients. The perceptual quantization of the residual is developed through the use of ASF. The quantization parameters of the residual and the predictor coefficients were jointly optimized; by means of both squared error and perceptual quality measures; to find the sweet spot of the rate-distortion curve. PVC-SLP coding performance is evaluated using two publicly available databases that collectively comprise 1281 vibrotactile signals covering 193 material classes. Furthermore, we compare PVC-SLP with a recent vibrotactile compression method and show that PVC-SLP perceptually outperforms existing method by a sizable margin. Most recently, PVC-SLP has been selected to become part of the haptic codec standard currently under preparation by IEEE P1918.1.1, aka Haptic Codecs for the Tactile Internet.

THE EFFECT OF LIGHT MASSAGE ON PERIFERAL BLOOD CIRCULATION IN TUBERCULOSIS PATIENTS

ABSTRACT
 
 Tuberculosis is still a major problem in the health sector, including side effects from treatment Side effects from tuberculosis treatment that are often experienced include indigestion, nausea, joint pain, dizziness, redness, itching, redness of the skin, liver disorders, joint pain and paresthesia or tingling. Tingling caused by blood circulation is not smooth. Light massage is a massage therapy in the form of gentle movements on the soft tissues of the body including wiping and rubbing movements, this skin stimulus will provide a sense of comfort, relaxes tension in the muscles and increases blood circulation. The purpose of this study was to determine the effect of Light Massage therapy on peripheral blood circulation in tuberculosis patients. This study uses a true experiment pre and post control group design. The number of samples of this study were 30 respondents in the intervention group and 30 respondents in the control group. The study was conducted in the working area of ​​the Sokaraja Community Health Center. The sampling technique used is simple random sampling. The mean respondent was female (56.7%), with an intensive treatment phase (76.7%), mean Ankle Brachial Index (ABI) score in the intervention group 1.03 and the control group 1.06. There were no differences in ABI scores between the intervention and control groups. Administration of light massages interventions for 3 times has not been able to reduce the ankle brachial index score in tuberculosis patients. Further research needs to be done on ABI scores in patients with advanced treatment phases.

Nerve growth factor sensitizes nociceptors to C-fibre selective supra-threshold electrical stimuli in human skin.

Intradermal injection of 1µg nerve growth factor (NGF) causes sustained nociceptor sensitization. Slowly depolarizing electrical current preferentially activates C-nociceptors. We explored the differential contribution of A-delta and C-nociceptors in NGF-sensitized skin using slowly depolarizing transcutaneous electrical current stimuli, CO2 laser heat, mechanical impact, and A-fibre compression block. In 14 healthy volunteers, pain rating was recorded on a numeric scale at days 1-14 after NGF treatment. Ratings during A-fibre conduction block were investigated at days 3 and 7 post-NGF. Pain ratings to electrical, CO2 heat and mechanical impact stimuli were enhanced (>30%, p<.0005, ANOVA) at NGF-injection sites. Axon reflex erythema evoked by electrical stimulation was also larger at NGF-injection sites (p<.02, ANOVA). Diminution of pain during continuous (1min) sinusoidal current stimulation at 4Hz was less pronounced after NGF (p<.05, ANOVA). Pain ratings to electrical sinusoidal and mechanical impact stimuli during A-fibre conduction block were significantly elevated at the NGF sites compared to NaCl-treated skin (p<.05, ANOVA). NGF-induced sensitization of human skin to electrical and mechanical stimuli is primarily driven by C-nociceptors with little contribution from A-delta fibres. Less-pronounced accommodation during ongoing sinusoidal stimulation suggests that NGF could facilitate axonal spike generation and conduction in primary afferent nociceptors in humans. Further studies using this sinusoidal electrical stimulation profile to investigate patients with chronic inflammatory pain may allow localized assessment of skin C-nociceptors and their putative excitability changes under pathologic conditions. The application of novel slowly depolarizing electrical stimuli demonstrated a predominant C-nociceptor sensitization in NGF-treated skin. Increased pain ratings, larger axon reflex erythema and less accommodation of C-fibres to ongoing sinusoidal stimulation all indicated an enhanced nociceptor discharge after NGF. A-fibre conduction block had little effect on electrical and mechanical hyperalgesia skin in NGF-treated compared to NaCl-treated skin. This electrical stimulus profile may be applicable for patients with chronic inflammatory pain, allowing localized assessment of skin C-nociceptors and their putative excitability changes under pathologic conditions.

Pain Perception, Brain Connectivity, and Neurochemistry in Healthy, Capsaicin-Sensitive Subjects.

Most of the occupational exposure limits (OELs) are based on local irritants. However, exposure to much lower concentrations of irritant substances can also lead to health complaints from workers. Exposure to irritants is often accompanied by strong unpleasant odors, and strong odors might have distracting effects and hence pose a safety risk. The findings obtained in human exposure studies with chemically sensitive, stressed, or anxious persons suggest that their ability to direct attention away from the odorous exposure and to focus on a cognitive task is reduced. In addition, after repeated odor exposure, these persons show signs of sensitization, i.e., difficulties in ignoring or getting used to the exposure. The question arises as to whether certain health conditions are accompanied by a change in sensitivity to odors and irritants, so that these persons are potentially more distracted by odors and irritants and therefore more challenged in working memory tasks than nonsusceptible persons. In our study, susceptible persons with sensory airway hyperreactivity (“capsaicin-sensitive”) respond more strongly to mechanical skin stimuli than controls and show altered network connectivity. Capsaicin-sensitive subjects have a lower pain threshold and thus are more sensitive to mechanical skin stimuli. The intrinsic functional connectivity of their saliency network is higher, and the lower the GABAergic tone of the thalamus, the higher their pain sensitivity to mechanical stimuli. It seems that the increased communication between resting-state networks promotes a stronger perception of the sensory input signal. The results can be used to inform about actual risks (i.e., attention diversion and increased risk of accidents) and “pseudo” risks such as odor perception without a negative impact on one's well-being. This way, uncertainties that still prevail in the health assessment of odorous and sensory irritating chemicals could be reduced.

Tactile rendering based on skin stress optimization

We present a method to render virtual touch, such that the stimulus produced by a tactile device on a user's skin matches the stimulus computed in a virtual environment simulation. To achieve this, we solve the inverse mapping from skin stimulus to device configuration thanks to a novel optimization algorithm. Within this algorithm, we use a device-skin simulation model to estimate rendered stimuli, we account for trajectory-dependent effects efficiently by decoupling the computation of the friction state from the optimization of device configuration, and we accelerate computations using a neural-network approximation of the device-skin model. Altogether, we enable real-time tactile rendering of rich interactions including smooth rolling, but also contact with edges, or frictional stick-slip motion. We validate our algorithm both qualitatively through user experiments, and quantitatively on a BioTac biomimetic finger sensor.

Efektifitas Teknik Distraksi Musik Klasik Mozart Untuk Mengurangi Nyeri Pada Pasien Post Operasi Fraktur

Most fractures are caused by traffic accidents with an estimated number of fractures in the world between 1 and 2.9 million with different age classifications. Each fracture will always undergo surgery followed by administering analgesics to reduce pain during the surgery. Non-pharmacological management to deal with pain consists of various physical treatment measures including skin stimulus, electrical nerve stimulation of the skin, acupuncture. The purpose of the study was to assess the effect of giving classical music mozart in reducing fracture pain in the Dahlia Room of Arifin Achmad Hospital Pekanbaru. Quasy Experiment Research Design, non randomized control group pretest postest design. The research sample was 30 respondents, with a sampling technique accidental sampling. The study was analyzed univariately and bivariately with the Wilcoxon and Man Whitney test. Testing the reduction in the degree of fracture pain in the control and experimental groups obtained the mean value of the experiment 6.71 post experiment 2.66 control value pre 6.35 and control post 6.48 with a value of ρ value 0.000 means that there is an influence of giving classical music mozart to fracture pain. Hopefully it can be used as a reference in providing mozart classical music distraction techniques to reduce pain in postoperative fracture patients

A New Rat Model of Thalamic Pain Produced by Administration of Cobra Venom to the Unilateral Ventral Posterolateral Nucleus

Background: Thalamic pain is a neuropathic pain syndrome that occurs as a result of thalamic damage. It is difficult to develop therapeutic interventions for thalamic pain because its mechanism is unclear. To better understand the pathophysiological basis of thalamic pain, we developed and characterized a new rat model of thalamic pain using a technique of microinjecting cobra venom into the ventral posterolateral nucleus (VPL) of the thalamus. Objectives: This study will establish a new thalamic pain rat model produced by administration of cobra venom to the unilateral ventral posterolateral nucleus. Study Design: This study used an experimental design in rats. Setting: The research took place in the laboratory at the Aviation General Hospital of China Medical University and Beijing Institute of Translational Medicine. Methods: Male Sprague-Dawley rats were subjected to the administration of cobra venom or saline into the left VPL. The development of mechanical hyperalgesia and changes in pain-related behaviors and motor function were measured after intrathalamic cobra venom microinjection using the von Frey test, video recording, and cylinder test, respectively. On postoperative days 7 to 35, both electroacupuncture and pregabalin (PGB) were administered to verify that the model reproduced the findings in humans. Moreover, the organizational and structural alterations of the thalamus were examined via transmission electron microscopy (TEM). Results: The threshold for mechanical stimuli in the left facial skin was significantly decreased on day 3 after thalamic pain modeling as compared with pre-venom treatment. Furthermore, the ultrastructural alterations of neurons such as indented neuronal nuclei, damaged mitochondria and endoplasmic reticulum, and dissolved surrounding tissues were observed under TEM. Moreover, electroacupuncture treatment ameliorated mechanical hyperalgesia, pain-like behaviors, and motor dysfunction, as well as restore normal structures of neurons in the thalamic pain rat model. However, no such beneficial effects were noted when PGB was administered. Limitations: The pathophysiological features were different from the present model and the patients in clinical practice (in most cases strokes, either ischemic or hemorrhagic). Conclusion: The cobra venom model may provide a reasonable model for investigating the mechanism of thalamic pain and for testing therapies targeting recovery and pain after thalamic lesions.

Preceding Administration of Minocycline Suppresses Plastic Changes in Cortical Excitatory Propagation in the Model Rat With Partial Infraorbital Nerve Ligation.

Neuropathic pain is known to be attributable to the injured nerve, a postoperative problem induced by surgery. The infraorbital nerve (ION), a branch of the trigeminal nerve, innervates to the facial and oral regions and conveys somatosensory information to the central nervous system. The partial ligation of ION (pl-ION) is a method to mimic chronic trigeminal neuropathic pain and behavioral abnormality. To counteract induction of such abnormal pain, the effective pharmacological treatment is desired. Although recent studies have revealed the molecular mechanisms regarding chronic pain, estimation of the effectiveness of the pharmacological treatment has not been well-provided especially in the central nervous system so far. Here we examined whether pl-ION induces plastic changes in the cerebral cortex and investigated effects of minocycline on the cortical plastic changes. We performed the pl-ION to Wistar male rats (4–5 weeks old), and confirmed a mechanical nocifensive behavior in response to the mechanical stimulation with von-Frey filaments. The withdrawal threshold to mechanical stimuli of the whisker pad was decreased 1 day (1 d) after pl-ION, which continued up to 14 d after pl-ION, suggesting that pl-ION model rats presented allodynia and enhanced the response sustained at least for 14 d after pl-ION. Next, cerebrocortical activities were evaluated 3 d after pl-ION (3d-pl-ION) by the optical imaging with a voltages-sensitive dye, RH1691, to quantify the response to electrical stimulation of the whisker pad skin, mandibular molar dental pulp, and mentum skin. Electrical stimulation to the whisker pad skin induced smaller excitation in the primary sensory cortex (S1) of 3d-pl-ION in comparison to that in the sham. In contrast, cerebral cortical responses to the mandibular molar dental pulp and mentum skin stimuli increased both in S1, and the secondary somatosensory and insular oral region (S2/IOR) after pl-ION. Administration of minocycline (30 mg/kg/d) from 1 d before to 2 d after pl-ION partially recovered the pl-ION-induced changes in cortical excitation in S1 and S2/IOR in 3d-pl-ION. These results suggest that somatosensory and insular cortical excitation is changed by pl-ION, and the preceding injection of minocycline counteracts the plastic changes in the cortical activities.

Gentle Perineal Skin Stimulation for Control of Nocturia.

One of the major causes of nocturia is overactive bladder (OAB). Somatic afferent nerve stimuli are used for treating OAB. However, clinical evidence for the efficacy of this treatment is insufficient due to the lack of appropriate control stimuli. Studies on anesthetized animals, which eliminate emotional factors and placebo effects, have demonstrated an influence of somatic stimuli on urinary bladder functions and elucidated the underlying mechanisms. In general, the effects of somatic stimuli are dependent on the modality, location, and physical characteristics of the stimulus. Recently we showed that gentle stimuli applied to the perineal skin using a soft elastomer roller inhibited micturition contractions to a greater extent than a roller with a hard surface. Studies aiming to elucidate the neural mechanisms of gentle stimulation-induced inhibition reported that 1-10 Hz discharges of low-threshold cutaneous mechanoreceptive Aβ, Aδ, and C fibers evoked during stimulation with an elastomer roller inhibited the micturition reflex by activating the spinal cord opioid system, thereby reducing both ascending and descending transmission between bladder and pontine micturition center. The present review will provide a brief summary of (1) the effect of somatic electrical stimulation on the micturition reflex, (2) the effect of gentle mechanical skin stimulation on the micturition reflex, (3) the afferent, efferent, and central mechanisms underlying the effects of gentle stimulation, and (4) a translational clinical study demonstrating the efficacy of gentle skin stimuli for treating nocturia in the elderly with OAB by using the two roller types inducing distinct effects on rat micturition contractions. Anat Rec, 302:1824-1836, 2019. © 2019 American Association for Anatomy.

A newly identified nociresponsive region in the transitional zone (TZ) in rat sensorimotor cortex

The primary somatosensory cortex (S1) comprises a number of functionally distinct regions, reflecting the diversity of somatosensory receptor submodalities innervating the body. In particular, two spatially and functionally distinct nociceptive regions have been described in primate S1 (Vierck et al., 2013; Whitsel et al., 2019). One region is located mostly in Brodmann cytoarchitectonic area 1, where a subset of neurons exhibit functional characteristics associated with myelinated Aδ nociceptors and perception of 1st/sharp, discriminative pain. The second region is located at the transition between S1 and primary motor cortex (M1) in area 3a, where neurons exhibit functional characteristics associated with unmyelinated C nociceptors and perception of 2nd/slow, burning pain. To test the hypothesis that in rats the transitional zone (TZ) – which is a dysgranular region at the transition between M1 and S1 – is the functional equivalent of the nociresponsive region of area 3a in primates, extracellular spike discharge activity was recorded from TZ neurons in rats under general isoflurane anesthesia. Thermonoxious stimuli were applied by lowering the contralateral forepaw or hindpaw into a 48–51 °C heated water bath for 5–10 s. Neurons in TZ were found to be minimally affected by non-noxious somatosensory stimuli, but highly responsive to thermonoxious skin stimuli in a slow temporal summation manner closely resembling that of nociresponsive neurons in primate area 3a. Selective inactivation of TZ by topical lidocaine application suppressed or delayed the nociceptive withdrawal reflex, suggesting that TZ exerts a tonic facilitatory influence over spinal cord neurons producing this reflex. In conclusion, TZ appears to be a rat homolog of the nociresponsive part of monkey area 3a. A possibility is considered that this region might be primarily engaged in autonomic aspects of nociception.

Development of Universal Method for Skin Stimulus Determination by Epidermal Keratinocyte Mitochondria as a Forefront of Sensory System for Homeostasis Maintenance

Development of Universal Method for Skin Stimulus Determination by Epidermal Keratinocyte Mitochondria as a Forefront of Sensory System for Homeostasis Maintenance