Changes In Sensory Thresholds Research Articles

Quantifying sensory thresholds along the migraine cycle: An exploratory longitudinal study.

To date, a number of studies on migraine have cross-sectionally evaluated sensory sensitivity with aversion thresholds/scores along the migraine cycle, reporting a decreased tolerance to sensory stimuli in different sensory modalities. Our hypothesis was that patients with migraine would exhibit heightened sensitivity to sound, light, touch and smell on days where they reported greater headache intensity. This is an exploratory, longitudinal study, carried out over the course of 27 days. Aversion thresholds or scores to sound, light, touch and smell were quantified in six patients with migraine (11.33 ± 6.53 headache days/month). Patients reported an increased sensitivity to light (padj = 0.0297), touch (padj = 0.0077), and smell (padj = 0.0201) on days with higher headache intensity. However, a greater sensitivity to sound on days with higher headache intensity was only reported when anxiety levels were high (padj = 1.4e-06). Interestingly, variable levels of tolerance to bothersome light over time can also influence the correlation between light sensitivity and headache intensity (padj = 1.4e-06). Based on the present findings, future longitudinal studies evaluating sensory threshold changes along the migraine cycle in patients with migraine should account for the increased tolerance to bothersome light over time as well as the effect of anxiety on auditory sensitivity.

What is the analgesic range of acupuncture stimulus for treating acute pain?

Since the analgesic effect of acupuncture stimulation is derived from different mechanisms depending on the type of pain, it is important to know which acupuncture points to stimulate. In this study, to confirm the effect of acupuncture stimulation on acute pain from a neurological point of view, somatosensory evoked potential and sensory threshold changes were evaluated to identify the nerve range that is affected by acupuncture stimulation on LI4 (Hapgok acupuncture point, of the radial nerve) during acute pain. The subjects were 40 healthy men and women aged 19-35 years. The study was designed as a randomly controlled, crossover trial with acupuncture stimulation at LI4 as the intervention. The washout period for acupuncture stimulation was 2 weeks, and the subjects were divided into two groups, i.e., an acupuncture stimulation group and a nonstimulation group, with 10 men and 10 women in each group. Somatosensory evoked potential measurement was carried out for 5 min by alternately applying 2 HZ-pulse electrical stimulation to the thumb and the little finger of the hand acupunctured with a 64-channel electroencephalogram. The verbal rating scale was used before and after each acupuncture stimulation session. The results of the study confirmed that the somatosensory evoked potential amplitude value of the thumb was significantly decreased and that the intensity of sensory stimulation corresponding to a verbal rating scale score of 6 was significantly increased only in the thumb after acupuncture stimulation. Therefore, the results show that acupuncture treatment for acute pain is more effective when direct acupuncture stimulation is applied to the painful area.

Repetitive sensorimotor mu-alpha phase-targeted afferent stimulation produces no phase-dependent plasticity related changes in somatosensory evoked potentials or sensory thresholds.

Phase-dependent plasticity has been proposed as a neurobiological mechanism by which oscillatory phase-amplitude cross-frequency coupling mediates memory process in the brain. Mimicking this mechanism, real-time EEG oscillatory phase-triggered transcranial magnetic stimulation (TMS) has successfully induced LTP-like changes in corticospinal excitability in the human motor cortex. Here we asked whether EEG phase-triggered afferent stimulation alone, if repetitively applied to the peaks, troughs, or random phases of the sensorimotor mu-alpha rhythm, would be sufficient to modulate the strength of thalamocortical synapses as assessed by changes in somatosensory evoked potential (SEP) N20 and P25 amplitudes and sensory thresholds (ST). Specifically, we applied 100 Hz triplets of peripheral electrical stimulation (PES) to the thumb, middle, and little finger of the right hand in pseudorandomized trials, with the afferent input from each finger repetitively and consistently arriving either during the cortical mu-alpha trough or peak or at random phases. No significant changes in SEP amplitudes or ST were observed across the phase-dependent PES intervention. We discuss potential limitations of the study and argue that suboptimal stimulation parameter choices rather than a general lack of phase-dependent plasticity in thalamocortical synapses are responsible for this null finding. Future studies should further explore the possibility of phase-dependent sensory stimulation.

Feasibility of quantitative sensory testing in juvenile idiopathic arthritis

ObjectiveJuvenile Idiopathic Arthritis (JIA) is a childhood-rheumatic disease with pain as a major early complaint, and in 10–17% pain remains a major symptom. Very few data exist on sensory threshold changes at the knee in JIA, a location in which inflammation often manifests. We determined whether JIA is associated with sensory threshold changes at the knee by using Quantitative Sensory Testing (QST) and established reference values at the knee of children.MethodsSixteen patients with JIA aged 9–18 years with one affected knee and a patient-reported pain by Visual Analog Scale (VAS) > 10 on a 0–100 scale, and 16 healthy controls completed the study and were included for the analysis. QST was assessed in compliance with the German Research Network on Neuropathic Pain (DFNS) standard. Disease severity was determined using Juvenile Disease Activity Score (JADAS. Perceived pain was assessed with a visual analogue scale(0–100). Feasibility of QST was tested in patients aged 6–9.ResultsUnder the age of 9, QST testing showed not to be feasible in 3 out of 5 JIA patients. Patients with JIA aged 9 and older reported an average VAS pain score of 54.3. QST identified a significant reduction in pressure pain threshold (PPT) and increase in cold detection threshold (CDT) compared to healthy controls. PPT is reduced in both the affected and the unaffected knee, CDT is reduced in the unaffected knee, not the affected knee.ConclusionIn a Dutch cohort of Patients with JIA, QST is only feasible from 9 years and up. Also, sensory threshold changes at the knee are restricted to pressure pain and cold detection thresholds in Patients with JIA.PerspectiveThis article shows that in a Dutch population, the extensive QST protocol is only feasible in the age group from 9 years and older, and a reduced set of QST tests containing at least pressure pain thresholds and cold detection thresholds could prove to be better suited to the pediatric setting with arthritis.

Stress sensitivity and cutaneous sensory thresholds before and after neuropathic injury in various inbred and outbred rat strains

Chronic pain is associated with altered affective state, stress, anxiety and depression. Conversely, stress, anxiety and depression can all modulate pain perception. The relative link between these behavioural constructs in different inbred and outbred rat strains, known to be variously hypo/hyperresponsive to stress has not been determined. Hindpaw sensory thresholds to repeated mechanical (von Frey filament and electronic Randall Selitto) and thermal (Hargreaves, cold plate and hot plate) stimulation were routinely assessed over three weeks in non-injured male rats of the following strains; WKY, LEW, F344, Hsd:SD and Crl:SD. Thereafter, threshold responses to Spared Nerve Injury (SNI) were assessed using von Frey, pin prick and Hargreaves testing in the same strains over a three month period. Finally, anxiolytic efficacy of the benzodiazepine drug diazepam was assessed using the Elevated Plus Maze (EPM), as a surrogate index of functional plasticity of circuits involved in affective processing. Repeated nociceptive testing was associated with distinct strain-dependent changes in sensory thresholds in naïve rats; stress-hyporesponsive LEW rats presented with a mechanical/thermal hyperalgesia phenotype, whereas stress-hyperresponsive WKY rats presented with an unexpected heat/cold hypoalgesia phenotype. After SNI, LEW rats showed minimal signs of neuropathic sensitivity. Diazepam was anxiolytic in all tested strains with the exception of LEW rats reflecting distinct inherent affective processing only in this strain. The contribution of stress reactivity to nociceptive sensory profiles appears to vary in the absence or presence of neuropathic injury. Intriguingly, the functional responsiveness of affective state prior to injury may be a predisposing factor to developing chronic pain.

Migraine understood as a sensory threshold disease.

Migraine encompasses a broader spectrum of sensory symptoms than just headache. These "other" symptoms, eg, sensory phobias, cognitive and mood changes, allodynia, and many others indicate an altered sensitivity to sensory input which can be measured, in principle, by quantifying sensory threshold changes longitudinally over time. Photophobia, for example, can be quantified by investigating the discomfort thresholds towards the luminance of light. The aim of this review is to look into how thresholds change in patients with migraine. We performed a PubMed search up to June 2018 targeting all peer-reviewed articles evaluating the changes in threshold, sensory phobia, or sensitivity in patients with migraine. Migraineurs, in general, exhibit lower sensory thresholds compared with healthy controls. These threshold changes seem to follow the different phases during a migraine cycle. In general, thresholds reach a nadir when the headache starts (the ictal phase), rise after the headache ends, and then gradually descend towards the next attack. The sensory modality of measurement-mechanical, thermal, or nociceptive-and the location of measurement-trigeminal vs somatic dermatome-also influence the sensory threshold. Functional imaging studies provide evidence that the hypothalamo-thalamo-brainstem network may be the driving force behind the periodic threshold changes. In summary, there is evidence in the literature that migraine could be understood as a periodic sensory dysregulation originating from the brain. Nevertheless, the interstudy discrepancy is still high due to different study designs and a lack of focus on distinct migraine phases. Further well-designed and harmonized studies with an emphasis on the cyclic changes still need to be conducted.

Chronic Central Pain Among Community-Dwelling Survivors of Moderate-to-Severe Traumatic Brain Injury: A Quantitative Sensory Testing Study.

Central pain associated with changes in sensory thresholds is one of the most enduring consequences of major trauma. Yet it remains sparsely studied among community-dwelling survivors of moderate-to-severe traumatic brain injury (TBI). To describe and compare thermal and mechanical sensory thresholds in home-based patients with and without central pain after moderate-to-severe TBI with a cohort of healthy controls. Cross-sectional. Thresholds for cold/heat detection, thermal pain, touch, and distorted sensation were gathered using quantitative sensory testing (QST). QST was performed on the painful and contralateral pain-free body regions in TBI participants with pain (TBI-P) and on both forearms in TBI participants without pain (TBI-NP) and healthy controls (HC). Central pain was characterized using the Brief Pain Inventory-Short Form. We tested 16 TBI-P patients, 17 TBI-NP patients, and 16 HC. Mean time since injury for TBI patients was 24 ± 15 months. TBI-P and TBI-NP patients showed significant loss in innocuous mechanical sensitivity compared to HC (F = 18.929; Bonferroni-adjusted p ≤ .001). Right-left differences in cold pain sensations were significantly larger in TBI-P than in TBI-NP and HC participants (F = 14.352; Bonferroni-adjusted p ≤ .001). Elevated heat sensitivity thresholds were also observed in TBI-P participants but remained within normal range. Damage to cutaneous mechanoreceptors is a necessary, but not sufficient, condition for the development of chronic central pain following TBI. Damage or incomplete recovery of cutaneous thermoreceptors may be a contributing factor to chronic pain after TBI.

Changes in Sensory Thresholds of the Pulp and Periodontal Ligaments after Standardized Tooth Clenching

Changes in Sensory Thresholds of the Pulp and Periodontal Ligaments after Standardized Tooth Clenching

Robert Lowell, Setting the River on Fire: A Study of Genius, Mania, and Character

Robert Lowell, Setting the River on Fire: A Study of Genius, Mania, and Character

Impact of sympathetic activation on pain threshold in human subjects

This study examined the effect of the sympathetic activation with the head-up tilt test (HUT) on electrocutaneous pain in 56 young normotensive volunteers. Systolic arterial blood pressure (SAP), diastolic arterial blood pressure (DAP), heart rate (HR), sensory and pain thresholds to electrocutaneous stimulation were measured 30s before (in supine position), during (at 10s, 90s, 3min and 5min) and 10min after HUT (in supine position). No relationship was found between resting BP and pain perception. HUT significantly increased DAP and HR, but did not change SAP. During HUT, both sensory and pain electrocutaneous thresholds were significantly increased, indicating reduced nociception. While changes in HR and changes in sensory threshold were correlated, no other correlation could be found between hemodynamic changes (DAP or HR) and changes in sensory and pain threshold. These results suggest that the mechanisms underlying the sympathetic adaptation to HUT and HUT-induced analgesia are different.

Effects of acupuncture on sensory perception: a systematic review and meta-analysis.

BackgroundThe effect of acupuncture on sensory perception has never been systematically reviewed; although, studies on acupuncture mechanisms are frequently based on the idea that changes in sensory thresholds reflect its effect on the nervous system.MethodsPubmed, EMBASE and Scopus were screened for studies investigating the effect of acupuncture on thermal or mechanical detection or pain thresholds in humans published in English or German. A meta-analysis of high quality studies was performed.ResultsOut of 3007 identified articles 85 were included. Sixty five studies showed that acupuncture affects at least one sensory threshold. Most studies assessed the pressure pain threshold of which 80% reported an increase after acupuncture. Significant short- and long-term effects on the pressure pain threshold in pain patients were revealed by two meta-analyses including four and two high quality studies, respectively. In over 60% of studies, acupuncture reduced sensitivity to noxious thermal stimuli, but measuring methods might influence results. Few but consistent data indicate that acupuncture reduces pin-prick like pain but not mechanical detection. Results on thermal detection are heterogeneous. Sensory threshold changes were equally frequent reported after manual acupuncture as after electroacupuncture. Among 48 sham-controlled studies, 25 showed stronger effects on sensory thresholds through verum than through sham acupuncture, but in 9 studies significant threshold changes were also observed after sham acupuncture. Overall, there is a lack of high quality acupuncture studies applying comprehensive assessments of sensory perception.ConclusionsOur findings indicate that acupuncture affects sensory perception. Results are most compelling for the pressure pain threshold, especially in pain conditions associated with tenderness. Sham acupuncture can also cause such effects. Future studies should incorporate comprehensive, standardized assessments of sensory profiles in order to fully characterize its effect on sensory perception and to explore the predictive value of sensory profiles for the effectiveness of acupuncture.

Somatosensory Abnormalities for Painful and Innocuous Stimuli at the Back and at a Site Distinct from the Region of Pain in Chronic Back Pain Patients

Chronic low back pain (CLBP) was shown to be associated with pathophysiological changes at several levels of the sensorimotor system. Changes in sensory thresholds have been reported but complete profiles of Quantitative Sensory Testing (QST) were only rarely obtained in CLBP patients. The aim of the present study was to investigate comprehensive QST profiles in CLBP at the painful site (back) and at a site distinct from their painful region (hand) and to compare these data with similar data in healthy controls. We found increased detection thresholds in CLBP patients compared to healthy controls for all innocuous stimuli at the back and extraterritorial to the painful region at the hand. Additionally, CLBP patients showed decreased pain thresholds at both sites. Importantly, there was no interaction between the investigated site and group, i.e. thresholds were changed both at the affected body site and for the site distinct from the painful region (hand). Our results demonstrate severe, widespread changes in somatosensory sensitivity in CLBP patients. These widespread changes point to alterations at higher levels of the neuraxis or/and to a vulnerability to nociceptive plasticity in CLBP patients.

Estimating Efficacy and Drug ED50's Using von Frey Thresholds: Impact of Weber's Law and Log Transformation

The use of von Frey filaments, originally developed by Maximilian von Frey, has become the cornerstone for assaying mechanical sensitivity in animal models and is widely used for human assessment. While there are certain limitations associated with their use that make comparisons between studies not straightforward at times, such as stimulus duration and testing frequency, von Frey filaments provide a good measurement of mechanosensation. Here we describe the application of von Frey filaments to testing in animal models, specifically with respect to determining changes in sensory thresholds in a pain state using the Dixon up-down method. In a literature survey, we found that up to 75% of reports using this method analyze the data with parametric statistical analysis and of those that used nonparametric analysis, none took into account that mechanical sensation is perceived on a logarithmic scale (Weber's Law) when calculating efficacy. Here we outline a more rigorous analysis for calculating efficacy and ED50's from von Frey data that incorporates Weber's Law. We show that this analysis makes statistical and biological sense and provide a specific example of how this change affects data analysis that brings results from animal models more in line with clinical observations. PerspectiveThis focus article argues that analyzing von Frey paw withdrawal threshold data obtained by using the Dixon up-down method without considering Weber's Law is inappropriate. An analysis method that incorporates how mechanical sensation is perceived and how its application brings results from animal models more in line with clinical data is presented.

Differential effects on sensory functions and measures of epidermal nerve fiber density after application of a lidocaine patch (5%) on healthy human skin

Topical application of lidocaine is an effective approach for treatment of post-herpetic neuralgia and other painful neuropathies. Lidocaine inhibits voltage-gated Na + channels and it most likely reduces excitability of cutaneous sensory neurons which can be hyperexcitable or spontaneously active in states of neuropathic pain. However, lidocaine and other local anesthetics also exert a pronounced neurotoxicity and they activate the irritant receptors TRPV1 and TRPA1. In this randomized and double-blinded study, we explored the ability of lidocaine patches (5%) to alter sensory function and epidermal nerve fiber density in skin of healthy volunteers. As assessed by quantitative sensory testing, significantly elevated thresholds for touch, pin prick pain and mechanically induced wind-up were observed in skin treated with lidocaine patches. These effects reversed to baseline values within 2 days after termination of the treatment. Pressure pain and thresholds for heat and cold-induced pain were not affected by the lidocaine patch. A moderate but significant decrease in epidermal nerve fiber density was observed in skin blister roofs obtained after 42 days of treatment with lidocaine patches. The placebo patch did not induce any changes in sensory thresholds or nerve fiber density. In conclusion, lidocaine patches seem to have differential effects on sensory modalities in healthy skin. A degeneration of epidermal nerve fibers has previously been demonstrated for patches containing the TRPV1-agonist capsaicin and our findings suggest that this effect might also be relevant for lidocaine patches. These data warrant further studies on molecular mechanisms mediating a relief of neuropathic pain by topical lidocaine.

Notch Signaling Modulates Sleep Homeostasis and Learning after Sleep Deprivation in Drosophila

The role of the transmembrane receptor Notch in the adult brain is poorly understood. Here, we provide evidence that bunched, a negative regulator of Notch, is involved in sleep homeostasis. Genetic evidence indicates that interfering with bunched activity in the mushroom bodies (MBs) abolishes sleep homeostasis. Combining bunched and Delta loss-of-function mutations rescues normal homeostasis, suggesting that Notch signaling may be involved in regulating sensitivity to sleep loss. Preventing the downregulation of Delta by overexpressing a wild-type transgene in MBs reduces sleep homeostasis and, importantly, prevents learning impairments induced by sleep deprivation. Similar resistance to sleep loss is observed with Notch(spl-1) gain-of-function mutants. Immunohistochemistry reveals that the Notch receptor is expressed in glia, whereas Delta is localized in neurons. Importantly, the expression in glia of the intracellular domain of Notch, a dominant activated form of the receptor, is sufficient to prevent learning deficits after sleep deprivation. Together, these results identify a novel neuron-glia signaling pathway dependent on Notch and regulated by bunched. These data highlight the emerging role of neuron-glia interactions in regulating both sleep and learning impairments associated with sleep loss.

Reliability of the Semmes Weinstein Monofilaments to measure coetaneous sensibility in the feet of healthy subjects

Purpose. To determine the intrarater-reliability, interrater-reliability and normal reference scores of the Semmes Weinstein Monofilament test (SWM) of the feet of healthy subjects. In addition, the stability of the SWM for prospective use was assessed by determining systematic changes in sensory thresholds.Methods. Interrater-reliability was assessed on five locations of the plantar side of both feet using monofilaments 1.65, 2.36, 2.44, 2.83, 3.22, 3.61, 3.84, 4.08, 4.31, 5.56, 6.65 in 60 healthy subjects by two or three investigators (test day 1). Intrarater-reliability and systematic changes in sensory thresholds were assessed 3 weeks later (test day 22) by one investigator.Results. Median interrater-reliability for the five test locations for both feet was poor to moderate. Median intrarater-reliability was good for the left foot and poor to moderate for the right foot. Significantly lower median sensory thresholds were found for the first SWM measurement at test day 22 compared to the first and second measurement of test day 1. Given the observed reliability of the SWM, a normal sensory score for the feet was situated between monofilament 3.22 and 4.08.Conclusions. The SWM are reliable when measured by one researcher. Systematic changes in sensory thresholds were observed; therefore, the stability of the SWM for use in prospective studies could not be verified.

Randomized controlled pilot study: Quantitative sensory testing in patients with back pain before and after Gua Sha massage

Question Permanent nociceptive influx may lead to functional changes in the nervous system, i.e. hyperalgesia and allodynia occur. These processes are suspected to contribute substantially to the ongoing pain process. Reflex therapies, like the Gua Sha, a traditional Chinese massage technique preferentially used in the treatment of back pain, are supposed to affect the transmission and processing of sensory information on receptor and spinal level [1] . If so one could assume that the Gua Sha massage should not only decrease the pain level itself, but also change sensory thresholds in the affected areas. In order to test this, we applied the Gua Sha massage in patients with chronic back pain and evaluated sensory threshold changes. Methods Thirty patients with chronic back pain (mean age 50.3±10.1 years) were randomized to treatment group (TG) or waiting list control group (WLC). At T1 all patients rated their pain on a 0–10 VAS scale. Baseline sensory testing was then conducted, followed by Gua Sha massage for the TG. Seven days later (T2) sensory testing was repeated and the WLC received Gua Sha. Testing included determination of mechanical detection threshold (MDT), pressure pain threshold (PPT) and vibration detection threshold (VDT) as described in the Quantitative Sensory Testing procedure (QST) by Rolke et al. [2] at the site of maximal pain, 10 cm next to the pain maximum and two control areas. In accordance to the QST procedure MDT and PPT scores were logarithmized. For further analysis, differences between T1 and T2 were compared between TG and WLC. Results First results show a significant decrease in mean pain ratings for the TG compared with the WLC ( p p Conclusions GuaSha not only decreased pain intensity for 35% on average compared with 4.6% increase in the WLC. TG also showed increased MDT and PPT at 10 cm next to the pain maximum. Together with the steady thresholds in both control areas this can be interpreted as the result of functional changes in the sensitized area. It appears that Gua Sha reduced allodynia in the pain surrounding area.

The Efficacy of Six Local Anesthetic Formulations Used for Posterior Mandibular Buccal Infiltration Anesthesia

The authors conducted a randomized, double-blind clinical trial to evaluate pulpal anesthesia achieved after mandibular infiltration of five commonly marketed dental local anesthetic formulations as compared with a control formulation of lidocaine with epinephrine. The authors evaluated 2 percent lidocaine with 1:100,000 epinephrine (L100) against 4 percent articaine with 1:100,000 epinephrine (A100), 4 percent articaine with 1:200,000 epinephrine (A200), 4 percent prilocaine with 1:200,000 epinephrine (P200), 3 percent mepivacaine without vasoconstrictor (Mw/o) and 0.5 percent bupivacaine with 1:200,000 epinephrine (B200). This repeated-treatment trial involved 18 healthy participants. The investigators administered mandibular infiltration injections (six sessions per participant) of 0.9 milliliters of anesthetic into the buccal fold adjacent to the distal root of the mandibular first molar. The authors determined anesthetic efficacy across a 20-minute period by measuring changes in sensory threshold to electrical pulp test (EPT) stimulation. Twelve female and six male participants (mean age, 24.9 years; range, 18-53 years) completed the study. The maximum mean increase from baseline of EPT measurements for the six formulations were 43.5 percent for L100, 44.8 percent for B200, 51.2 percent for P200, 66.9 percent for A200, 68.3 percent for Mw/o and 77.3 percent for A100 (A100 versus L100, P = .029). Adverse reactions were minor and not formulation dependent. The authors found that mandibular infiltration with 0.9 mL of the tested dental anesthetics could induce only partial pulpal anesthesia, a level likely to be inadequate for most dental procedures. When compared with L100, only the A100 induced statistically greater pulpal anesthesia after mandibular buccal infiltration.

Motor cortex rTMS in chronic neuropathic pain: pain relief is associated with thermal sensory perception improvement

Background: Improvement in sensory detection thresholds was found to be associated with neuropathic pain relief produced by epidural motor cortex stimulation with surgically implanted electrodes. Objective: To determine the ability...

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The Neurometer is a sensory threshold testing device that has been used to diagnose sensory deficits in humans, but few studies describe its utility in detecting changes in sensory threshold after pharmacological intervention. These studies were done to assess its utility in that capacity in a pre-clinical species. Male Sprague-Dawley rats (200-250 g) were habituated to a tube-type restrainer before testing. A stimulating electrode was placed on the tail and a reference electrode placed on a depilated portion of the flank.