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OBJECTIVES: Widespread pressure hyperalgesia, facilitated temporal summation of pain (TSP), and impaired conditioned pain modulation (CPM) have been found in knee osteoarthritis (KOA) patients compared with controls and these parameters have further been suggested to be altered in the elderly. This study investigated the influence of age on pressure hyperalgesia, TSP, and CPM in patients with KOA and controls.METHODS: One-hundred-thirty-three severe KOA patients and 50 age and sex-matched asymptomatic controls were assessed by cuff algometry and handheld pressure algometry. Pain sensitivity was assessed around the head of the gastrocnemius muscle to identify mild pain detection (MPDT) and tolerance (PTT) threshold. TSP was assessed by visual analogue scale (VAS) scores of the pain evoked by 10 repetitive cuff stimulations. CPM was assessed as the difference in PTT before and during cuff-induced tonic arm pain. Pressure pain thresholds (PPTs) were assessed by handheld algometry at the tibialis anterior muscle. Two subgroups were analyzed in the age range below and above 65 years. Pearson correlations between age and pain parameters were applied.RESULTS: Patients demonstrated reduced MPDT, PTT and PPT (PDISCUSSION: Pressure hyperalgesia was affected by age whereas dynamic pain mechanisms such as TSP and CPM were unaffected suggesting that these parameters are robust for a larger age range and reliable for long-term follow up studies.

Temporal summation of second pain (TSSP) is a psychophysical indication of a central pain encoding mechanism, potentially enhanced in pathological pain conditions. Low-frequency repetitive stimulation of unmyelinated (C) nociceptors results in a progressive increase of pain intensity when thermal stimulation intensity remains constant. However, when using different methods of nociceptive delivery to the skin, regularity as well as rate of pain enhancement with repetition varies between experiments. Specifically, repetitive ramping up and down from a neutral to a painful temperature has produced weak and inconsistent pain summation. In contrast, repetitive contact of the skin with a preheated probe has generated substantial pain summation. In the present study, TSSP by the intermittent contact with a preheated thermode and constant contact, ramp and hold methods were compared during 10 iterations of stimulation of glabrous skin of the hand or hairy forearm skin, with an onset to onset interval of 3.3 seconds and stimulus interval of .8 seconds. Significantly greater TSSP was observed for intermittent contact stimulation at both sites (P .001). Differential activation of myelinated and unmyelinated nociceptors by ramping and tapping may account for different rates of temporal summation of heat pain.This article presents direct evidence suggesting the constant contact, ramp and hold stimulus may underestimate the level of TSSP. This evidence suggests the re-evaluation of stimulation techniques used for temporal summation tests, especially within clinical models.

Introduction The mechanism of action of non-invasive vagal nerve stimulation in the treatment of migraine is elusive. We studied its effect in a human model of pain, the nociceptive withdrawal reflex. Methods We enrolled 10 healthy subjects who underwent active non-invasive vagal nerve stimulation and sham treatment in a randomized, cross-over, sham-controlled study. Non-invasive vagal nerve stimulation was delivered with gammaCore®. The assessment of the nociceptive withdrawal reflex was performed at baseline (T0) and at 5 (T5) and 30 (T30) minutes after stimulation. Results Non-invasive vagal nerve stimulation significantly increased the reflex threshold to single stimulus at both T5 and T30 and the temporal summation threshold at T30. Sham treatment did not modify any parameters. Discussion These findings are consistent with a modulation of central descending pathways for pain control. An altered spinal and supraspinal control of pain has been described in primary headache, so this effect may partially explain the therapeutic effect of non-invasive vagal nerve stimulation.

Temporal summation is an important feature of the visual system which combines visual signals that arrive at different times. Previous research estimated complete summation to last for 100ms for stimuli judged "just detectable." We measured the full range of temporal summation for much weaker stimuli using a new paradigm and a novel light source, developed in the field of quantum optics for generating small numbers of photons with precise timing characteristics and reduced variance in photon number. Dark-adapted participants judged whether a light was presented to the left or right of their fixation in each trial. In Experiment 1, stimuli contained a stream of photons delivered at a constant rate while the duration was systematically varied. Accuracy should increase with duration as long as the later photons can be integrated with the proceeding ones into a single signal. The temporal integration window was estimated as the point that performance no longer improved, and was found to be 650ms on average. In Experiment 2, the duration of the visual stimuli was kept short (100ms or

The purpose of this study was to compare the immediate change in temporal summation of heat pain (TSP) between spinal manipulation (SMT) and spinal mobilization (MOB) in healthy volunteers. Ninety-two volunteers (24 male; 23.8 ± 5.3 years) were randomized to receive SMT, MOB, or no treatment (REST) for 1 session. Primary outcomes were changes in TSP, measured at the hand and foot, immediately after the session. A planned subgroup analysis investigated effects across empirically derived TSP clusters. For the primary outcome there were no differences in the immediate change in TSP measured at the foot between SMT and MOB, however, both treatments were superior to the REST condition. In the subgroup analysis the response to a standard TSP protocol was best characterized by 3 clusters: 52% no change (n = 48, 52%); facilitatory response (n = 24, 26%), and inhibitory response (n = 20, 22%). There was a significant Time × Treatment group × Cluster interaction for TSP measured at the foot. The inhibitory cluster showed the greatest attenuation of TSP after SMT and MOB compared with REST. These data suggest lumbar manual therapies of different velocities produce a similar localized attenuation of TSP, compared with no treatment. Attenuation of localized pain facilitatory processes by manual therapies was greatest in pain-free individuals who show an inhibitory TSP response. Perspective The attenuation of pain facilitatory measures may serve an important underlying role in the therapeutic response to manual therapies. Identifying patients in pain who still have an inhibitory capacity (ie, an inhibitory response subgroup) may be useful clinically in identifying the elusive “manual therapy” responder.

Background Knee pain associated with osteoarthritis is a significant contributor to decreased physical function. Recent evidence supports the inter-individual heterogeneity associated with knee pain presentation, but whether there is similar heterogeneity in physical performance among these individuals has not been previously examined. The aim of the present study was to characterize the variability in physical performance profiles and the pain evoked by their performance (i.e., movement-evoked pain). Methods In a secondary analysis of the community-based study Understanding Pain and Limitations in Osteoarthritic Disease (UPLOAD), individuals (n = 270) completed functional, pain, psychological, and somatosensory assessments. Hierarchical cluster analysis was used to derive physical function profiles that were subsequently compared across several clinical, psychological and experimental pain measures. Results Our results support the hypothesis that among persons with knee OA pain, three different physical performance profiles exist with varying degrees of movement-evoked pain. Even as all three groups experienced moderate to severe levels of spontaneous knee pain, those individuals with the most severe movement-evoked pain and lowest physical functional performance also had the least favorable psychological characteristics along with increased mechanical pain sensitivity and temporal summation. Conclusions Our findings support the need for the assessment and consideration of movement-evoked pain during physical performance tasks as these have the potential to increase the value of functional and pain assessments clinically. The identification of the mechanisms driving pain burden within homogeneous groups of individuals will ultimately allow for targeted implementation of treatments consistent with a biopsychosocial model of pain.

Chronicity and recurrence in musculoskeletal shoulder pain are highly prevalent and can possibly be attributed to the concept of central sensitization. Available studies suggest a role for central sensitization in explaining chronic shoulder pain, but so far a comprehensive quantitative sensory testing (QST) protocol has not been used. The aim of this study was to gain knowledge on sensory processing and central pain modulatory mechanisms in patients suffering from chronic shoulder pain using such a QST protocol. Fifty study participants, including chronic shoulder pain patients and healthy controls, underwent a standardized, comprehensive psychophysical testing procedure. A static adapted QST protocol (including pressure algometry, vibration and mechanical detection) was applied. Thereafter, all subjects underwent dynamic measures of temporal summation and conditioned pain modulation. Questionnaires assessing psychosocial factors were completed by each subject. No significant differences (P >= .05) were found between patients and controls based on pressure algometry, vibration detection, mechanical detection, temporal summation, and conditioned pain modulation. Moderate positive correlations (r = .5) were found between pressure pain thresholds (PPTs) and the amount of sports participation. Weak-to-moderate negative correlations (r = −.3 à −.5) were found between PPTs and psychosocial factors such as pain catastrophizing. Based on these findings, we can conclude that central sensitization is no characteristic feature in chronic musculo-skeletal shoulder pain but can be present in individual cases.

Pain is the hallmark of sickle cell anemia (SCA), presenting as recurrent acute events or chronic pain. Central sensitization, or enhanced excitability of the central nervous system, alters pain processing and contributes to the maintenance of chronic pain. Individuals with SCA demonstrate enhanced sensitivity to painful stimuli however central mechanisms of pain have not been fully explored. We hypothesized that adults with SCA would show evidence of central sensitization as observed in other diseases of chronic pain. Methods We conducted a prospective study of static and dynamic quantitative sensory tests in 30 adults with SCA and 30 matched controls. Results Static thermal testing using cold stimuli showed lower pain thresholds (p = 0.04) and tolerance (p = 0.04) in sickle cell subjects, but not for heat. However, SCA subjects reported higher pain ratings with random heat pulses (p < 0.0001) and change in scores with temporal summation at the heat pain threshold (p = 0.002). Similarly, with the use of pressure pain stimuli, sickle cell subjects reported higher pain ratings (p = 0.04), but not higher pressure pain tolerance/thresholds or allodynia to light tactile stimuli. Temporal summation pain score changes using 2 pinprick probes (256 and 512 mN) were significantly greater (p = 0.004 and p = 0.008) with sickle cell, and delayed recovery was associated with lower fetal hemoglobin (p = 0.002 and 0.003). Conclusions Exaggerated temporal summation responses provide evidence of central sensitization in SCA. Implications The association with fetal hemoglobin suggests this known SCA modifier may have a therapeutic role in modulating central sensitization.

Sickle cell disease (SCD) is associated with episodes of severe vaso-occlusive pain beginning in infancy with a subset of patients with SCD transitioning to chronic pain. Response to experimental pain using quantitative sensory testing in these patients suggests altered pain processing. The objectives of this study were to characterize sensitivity to multiple modalities of experimental pain stimuli and to interrogate the relationship of psychological covariates, clinical pain burden, and pain-related outcomes to experimental pain sensitivity in children with SCD compared with healthy individuals of similar age and sex. Cross-sectional assessments of psychological characteristics were performed, and quantitative sensory testing methods were used to measure experimental pain sensitivity in children age 8 to 21 years. Anxiety, depressive symptoms, catastrophizing, and somatization were found to be associated with increased sensitivity to experimental pain stimuli. Increased frequency of painful episodes in SCD was associated with decreased sensitivity to heat pain and decreased mechanical temporal summation. These data suggest that careful consideration be given to psychological factors, age, sex, and clinical burden of pain when studying response to experimental pain in SCD. Perspective In this study of patients with SCD, a condition associated with recurrent acute or chronic pain, psychological factors such as depression, anxiety, and catastrophizing are associated with increased sensitivity to experimental pain stimuli. Further study is need to delineate the role of these factors in chronic SCD pain.

Introduction This study explored whether nociceptive (NS ) and autonomic nervous system (ANS) dysregulation and psychological distress (PD) where predictive of pain six months after primary total knee replacement for osteoarthritis. Methods: ANS regulation (heart rate variability), NS regulation (temporal summation and the conditioned pain modulation effect), PR (pain catastrophizing), and self-reported pain, stiffness and function, were e valuated preoperatively in 56 patients. Pain severity (WOMAC-pain subscale) in the operated knee measured 6 months after surgery was used as the primary outcome in an ANCOVA model to identify independent predictors of pain. Results The data of 47 patients (85.5%) could be analyzed. Postoperative pain severity six months after surgery was significantly associated with reduced heart rate variability () and tended to be related to a lower conditioned pain modulation effect, but only in females. Conclusion The findings of present study suggest the dysregulation of the ANS and NS may be predictive of chronic pain six months after primary total knee replacement and may be sex specific.

Background This study investigated the effects of medication overuse and withdrawal on modulation of pain processing in women with migraine. Temporal summation of laser-evoked thermal pain was used to measure the effects of conditioned pain modulation. Methods 36 female participants (12 healthy volunteers, 12 with episodic migraine and 12 with medication overuse headache) were included in a two session protocol. Medication overuse headache subjects were also tested three weeks after medication overuse headache withdrawal. Mechanical and laser-evoked thermal pain thresholds were measured on the back of the non-dominant hand where, later, temporal summation of laser-evoked thermal pain to repetitive thermal stimuli was elicited for 30 min, at an intensity producing moderate pain. Between the 10th and 20th minutes, the contralateral foot was immersed into a water bath at a not painful (30℃) or painfully cold (8℃; conditioned pain modulation) temperature. Results Episodic migraine, medication overuse headache and medication overuse headache withdrawal were associated with an increase in extracephalic temporal summation of laser-evoked thermal pain as compared to healthy volunteer subjects, while there was no alteration of laser-evoked thermal and mechanical extracephalic pain thresholds in these subjects. Conditioned pain modulation was highly efficient in temporal summation of laser-evoked thermal pain in healthy volunteer subjects, with a solid post-effect (reduction of pain). Conditioned pain modulation was still present, but reduced, in episodic migraine. By contrast, conditioned pain modulation was normal in medication overuse headache and strongly reduced in medication overuse headache withdrawal. Furthermore, in medication overuse headache withdrawal, the post-effect was no longer a decrease, but a facilitation of pain. Conclusions These data show that a decrease in conditioned pain modulation does not underlie medication overuse headache in women. On the contrary, medication overuse reinstated conditioned pain modulation in female migraine patients. They also identify different phenotypes of pain modulation in migraine patients. Registration number N° 2008-A00471-54.

The superior colliculus (SC) receives direct input from the retina and integrates it with information about sound, touch, and state of the animal that is relayed from other parts of the brain to initiate specific behavioral outcomes. The superficial SC layers (sSC) contain cells that respond to visual stimuli, whereas the deep SC layers (dSC) contain cells that also respond to auditory and somatosensory stimuli. Here, we used a large-scale silicon probe recording system to examine the visual response properties of SC cells of head-fixed and alert male mice. We found cells with diverse response properties including: (1) orientation/direction-selective (OS/DS) cells with a firing rate that is suppressed by drifting sinusoidal gratings (negative OS/DS cells); (2) suppressed-by-contrast cells; (3) cells with complex-like spatial summation nonlinearity; and (4) cells with Y-like spatial summation nonlinearity. We also found specific response properties that are enriched in different depths of the SC. The sSC is enriched with cells with small RFs, high evoked firing rates (FRs), and sustained temporal responses, whereas the dSC is enriched with the negative OS/DS cells and with cells with large RFs, low evoked FRs, and transient temporal responses. Locomotion modulates the activity of the SC cells both additively and multiplicatively and changes the preferred spatial frequency of some SC cells. These results provide the first description of the negative OS/DS cells and demonstrate that the SC segregates cells with different response properties and that the behavioral state of a mouse affects SC activity.SIGNIFICANCE STATEMENT The superior colliculus (SC) receives visual input from the retina in its superficial layers (sSC) and induces eye/head-orientating movements and innate defensive responses in its deeper layers (dSC). Despite their importance, very little is known about the visual response properties of dSC neurons. Using high-density electrode recordings and novel model-based analysis, we found several novel visual response properties of the SC cells, including encoding of a cell's preferred orientation or direction by suppression of the firing rate. The sSC and the dSC are enriched with cells with different visual response properties. Locomotion modulates the cells in the SC. These findings contribute to our understanding of how the SC processes visual inputs, a critical step in comprehending visually guided behaviors.

Individuals with greater borderline personality features may be vulnerable to chronic pain. Because pain is an unpleasant sensory and emotional experience, affect dysregulation as the core personality feature may be linked to pain hypersensitivity. Studies have found that greater borderline features are associated with increased intensity in clinical and experimental pain, and that depression mediates this increase. The current study further examined the association between borderline features and heat pain sensitivity, the contribution of affect dysregulation and the other borderline personality factors (identity problems, negative relationships, self-harming/impulsivity) to the association, and depression as a mediator. Additionally, we examined whether blunted sympathetic responses mediate the association between borderline features and temporal summation of second pain (TSSP). Thermal pain threshold, thermal TSSP and aftersensations pain were assessed in 79 healthy individuals with varying degrees of borderline features. TSSP is a proxy measure for central sensitization and refers to the gradual increase in pain to repeated nociceptive stimuli. A regression analysis showed that greater borderline features predicted greater TSSP (β = .22, p = .050, R2 = .05). Borderline features were unrelated to pain threshold and TSSP decay. A stepwise regression showed greater TSSP in individuals with greater borderline features was accounted for by the negative relationships factor rather than the affect dysregulation factor. The results of mediational analyses showed depression and blunted sympathetic skin conductance responses mediated the positive association between TSSP and borderline features.

Dopamine (DA), an important neurotransmitter and neuromodulator, plays important roles in neuronal physiological functions by activating G-protein-coupled DA D1 and/or D2 receptors. Previous studies have demonstrated that D1 receptors are functionally expressed in retinal neurons and glial cells, including ganglion cells. In this study, we explored the effects of D1 receptor activation on retinal ganglion cell (RGC) temporal summation and excitability in rat retinal slices using electrophysiological techniques. Bath application of the selective D1 receptor agonist SKF81297 increased the ratio of excitatory postsynaptic potentials (EPSPs) (EPSP5/EPSP1) within an EPSP train evoked by a train stimulation (five current pulses at 40Hz), which was blocked by co-application of SCH23390, a specific D1 receptor antagonist. Ba2+, an inwardly rectifying K+ channel (Kir) blocker, significantly suppressed the SKF81297-induced effect, whereas ZD7288, a specific hyperpolarization-activated cation current (Ih) blocker, showed a moderate inhibitory effect. The cAMP/protein kinase A (PKA) signaling pathway, but not phosphoinositide-specific phospholipase C (PI-PLC), mediated the SKF81297-induced modulation of EPSP temporal summation. Further experiments showed that SKF81297 suppressed Ba2+-sensitive Kir currents in RGCs. Additionally, SKF81297 increased the spontaneous firing frequency of RGCs, and caused depolarization of the cells with or without the presence of synaptic receptor blockers. In contrast, SKF81297 did not significantly change the frequency of miniature excitatory postsynaptic currents (mEPSCs) recorded in RGCs. Our results indicate that D1 receptor activation enhances the temporal summation of RGCs mainly by suppressing Kir currents through the cAMP/PKA signaling pathway, thus increasing the excitability of rat RGCs.

In this paper, ion-gel gated transistors based on solution-processed indium-gallium-zinc-oxide (In-Ga-Zn-O) semiconductors were fabricated. These transistors consisted of a spatial distribution configuration of multi-in-plane gates. Spike pluses applied on multi-in-plane gates are analogy to massive synaptic inputs from various dendritic positions. The basic neuromorphic functions, such as potentiation or depression behaviors, synaptic plasticity and frequency-dependent filtering, were demonstrated in these devices by applied a spiking on an in-plane gate. The output signal of neuromorphic devices is greatly relevant to the gate position-correlated input signal and the spatially-correlated information processing could advance the capacity of neuromorphic performance. Orientation selectivity was a broadly investigated phenomenon. More importantly, by using the spatial summation functions of dendritic integration, the orientation identification was successfully realized in our transistor with multi-in-plane gates. The spatially-correlated neuromorphic devices are exceedingly promising for the neural information processing and sensing.

Temporal summation of nociceptive inputs may be an important pathophysiological mechanism in temporomandibular disorders (TMD) pain; however, it remains unknown how natural jaw function relates to underlying pain mechanisms. This study evaluated changes in pain and movement patterns during repeated jaw movements in patients with painful temporomandibular joints (TMJ) compared with healthy controls. Twenty patients with TMD with TMJ pain, and an anterior disk displacement without reduction and 20 age- and gender-matched healthy volunteers were included. Participants performed 20 trials (4 × 5 sessions) of standardized and repeated mandibular movements, and scored the movement-associated pain intensity on 0 to 10 numeric rating scale in addition to measurements of jaw movements. Patients with TMJ pain reported higher baseline pain compared to the control group for all types of jaw movements (P = 0.001) and significant increases in numeric rating scale pain scores by repetition of jaw movements (P < 0.001), which was not observed in the control group (P > 0.05). Jaw total opening distance (P = 0.030), maximum opening velocity (P = 0.043) and average closing velocity (P = 0.044) in the TMJ pain group were significantly reduced during the repeated movements. In the control group, however, total opening distance (P = 0.499), maximum opening velocity (P = 0.064), and average closing velocity (P = 0.261) remained unchanged, whereas average opening velocity (P = 0.040) and maximum closing velocity (P = 0.039) increased. The study demonstrates that repeated jaw movements constitute a sufficient and adequate stimulation for triggering temporal summation effects associated with significant inhibition of motor function in painful TMJs. These findings have practical implications for diagnosis of TMD pain and for more mechanism-driven management protocols in the future.

Racial differences in endogenous pain facilitatory processes have been previously reported. Evidence suggests that psychological and behavioral factors, including depressive symptoms and sleep, can alter endogenous pain facilitatory processes. Whether depressive symptoms and sleep might help explain racial differences in endogenous pain facilitatory processes has yet to be determined. This observational, microlongitudinal study examined whether depressive symptoms and sleep were sequential mediators of racial differences in endogenous pain facilitatory processes. A total of 50 (26 African American and 24 non-Hispanic white) community-dwelling adults without chronic pain (mean 49.04 years; range 21–77) completed the Center for Epidemiological Studies Depression Scale prior to seven consecutive nights of sleep monitoring with actigraphy in the home environment. Participants subsequently returned to the laboratory for assessment of endogenous pain facilitation using a mechanical temporal summation protocol. Findings revealed greater depressive symptoms, poorer sleep efficiency, and greater temporal summation of mechanical pain in African Americans compared to non-Hispanic whites. In a sequential mediation model, greater depressive symptoms predicted poorer sleep efficiency (t = −2.55, p = .014), and poorer sleep efficiency predicted enhanced temporal summation of mechanical pain (t = −4.11, p

Older adults compared with younger adults are characterized by greater endogenous pain facilitation and a reduced capacity to endogenously inhibit pain, potentially placing them at a greater risk for chronic pain. Previous research suggests that higher levels of self-reported physical activity are associated with more effective pain inhibition and less pain facilitation on quantitative sensory tests in healthy adults. However, no studies have directly tested the relationship between physical activity behavior and pain modulatory function in older adults. This study examined whether objective measures of physical activity behavior cross-sectionally predicted pain inhibitory function on the conditioned pain modulation (CPM) test and pain facilitation on the temporal summation (TS) test in healthy older adults. Fifty-one older adults wore an accelerometer on the hip for 7 days and completed the CPM and TS tests. Measures of sedentary time, light physical activity (LPA), and moderate to vigorous physical activity (MVPA) were obtained from the accelerometer. Hierarchical linear regressions were conducted to determine the relationship of TS and CPM with levels of physical activity, while controlling for demographic, psychological, and test variables. The results indicated that sedentary time and LPA significantly predicted pain inhibitory function on the CPM test, with less sedentary time and greater LPA per day associated with greater pain inhibitory capacity. Additionally, MVPA predicted pain facilitation on the TS test, with greater MVPA associated with less TS of pain. These results suggest that different types of physical activity behavior may differentially impact pain inhibitory and facilitatory processes in older adults.

Purpose Goldmann size V (GV) test stimuli are less variable with a greater dynamic range and have been proposed for measuring contrast sensitivity instead of size III (GIII). Since GIII and GV operate within partial summation, we hypothesise that actual GV (aGV) thresholds could predict GIII (pGIII) thresholds, facilitating comparisons between actual GIII (aGIII) thresholds with pGIII thresholds derived from smaller GV variances. We test the suitability of GV for detecting visual field (VF) loss in patients with early glaucoma, and examine eccentricity‐dependent effects of number and depth of defects. We also hypothesise that stimuli operating within complete spatial summation (‘spatially equated stimuli’) would detect more and deeper defects. Methods Sixty normal subjects and 20 glaucoma patients underwent VF testing on the Humphrey Field Analyzer using GI‐V sized stimuli on the 30‐2 test grid in full threshold mode. Point‐wise partial summation slope values were generated from GI‐V thresholds, and we subsequently derived pGIII thresholds using aGV. Difference plots between actual GIII (aGIII) and pGIII thresholds were used to compare the amount of discordance. In glaucoma patients, the number of ‘events’ (points below the 95% lower limit of normal), defect depth and global indices were compared between stimuli. Results 90.5% of pGIII and aGIII points were within ±3 dB of each other in normal subjects. In the glaucoma cohort, there was less concordance (63.2% within ±3 dB), decreasing with increasing eccentricity. GIII found more defects compared to GV‐derived thresholds, but only at outermost test locations. Greater defect depth was found using aGIII compared to aGV and pGIII, which increased with eccentricity. Global indices revealed more severe loss when using GIII compared to GV. Spatially equated stimuli detected the greatest number of ‘events’ and largest defect depth. Conclusions Whilst GV may be used to reliably predict GIII values in normal subjects, there was less concordance in glaucoma patients. Similarities in ‘event’ detection and defect depth in the central VF were consistent with the fact that GIII and GV operate within partial summation in this region. Eccentricity‐dependent effects in ‘events’ and defect depth were congruent with changes in spatial summation across the VF and the increase in critical area with disease. The spatially equated test stimuli showed the greatest number of defective locations and larger sensitivity loss.

OBJECTIVES Pain sensitization in knee osteoarthritis (OA) is associated with greater symptom severity and poorer clinical outcomes. Measures that identify pain sensitization and are accessible to use in clinical practice have been suggested to enable more targeted treatments. This merits further investigation. This study examines the relationship between quantitative sensory testing (QST) and clinical measures of pain sensitization in people with knee OA. METHODS A secondary analysis of data from 134 participants with knee OA was performed. Clinical measures included: manual tender point count (MTPC), the Central Sensitization Inventory (CSI) to capture centrally mediated comorbidities, number of painful sites on a body chart, and neuropathic pain-like symptoms assessed using the modified PainDetect Questionnaire. Relationships between clinical measures and QST measures of pressure pain thresholds (PPTs), temporal summation, and conditioned pain modulation were investigated using correlation and multivariable regression analyses. RESULTS Fair to moderate correlations, ranging from -0.331 to -0.577 (P

Objectives Stretching is an intervention often used in various kinds of rehabilitation protocols and the effects on pain sensitivity has sparsely been investigated, especially when addressing potential effects on pain. The objective is to investigate the immediate effects of an axial and peripheral prolonged stretch on pressure pain sensitivity (PPT) and temporal summation (TS) on local and distal sites in healthy subjects. Methods Twenty-two healthy volunteers were recruited to participate in this pilot study. Two prolonged stretching protocols were performed: low back and wrist extensors stretches. PPT and pinprick TS were measured pre- and post-intervention at local and remote sites. Repeated measures analysis of variance (ANOVA) was used to examine the effects and significance of the interventions. Results The low back stretch induced an increase in PPT for both local and remote sites, and the wrist stretch produced a PPT increase only at the local site. TS did not change. Conclusions Low back stretching induced an increase in PPT at both local and remote sites whereas the wrist stretch only increased PPT locally, suggesting hypoalgesia at these sites. Further studies are needed to confirm the effect and mechanisms using randomised, controlled and parallel study design. Considering that pain sensitivity is different than clinical pain, results are difficult to extrapolate to clinical practice. Future studies testing clinical pain are needed to better understand the clinical implication of these results.

Background and aims: Pain is the primary symptom of chronic pancreatitis (CP), but methods for sensory testing and pain characterization have not previously been validated for clinical use. We present a clinically feasible method for the assessment and characterization of pain mechanisms in patients with CP based on quantitative sensory testing (QST). Methods: This was a cross-sectional, multicenter study of 122 control subjects without pancreatic disease and another 60 patients with painful CP. All subjects underwent standardized QST assessments including a cold pressor test, a conditioned pain modulation paradigm, repetitive pin-prick stimuli (temporal summation) and pressure stimulation of the upper abdominal (pancreatic) and control dermatomes. The effects of age and gender on QST assessment parameters were investigated and normative reference values based on quartile regression were derived and implemented in algorithms to categorize patients according to their patterns of central pain processing (normal vs. segmental sensitization vs. widespread sensitization). Results: Absolute pressure thresholds were subject to clinically relevant gender effects (all p < 0.001), while the remainder of QST parameters were unaffected by age and gender. The algorithm with the best discriminatory capacity showed good separation between patients and controls (p < 0.001); 50% of patients had normal central pain processing, 23% had evidence of segmental sensitization and 27% had evidence of widespread sensitization. Conclusion: We show normative reference values for a clinically feasible method for assessment and characterization of pain mechanisms in patients with CP. Application of this method streamlines the evaluation of pancreatic pain and may be used to inform treatment. Clinicaltrials.gov id: NCT03434392.

The shuffled (aka anonymous) model has recently generated significant interest as a candidate distributed privacy framework with trust assumptions better than the central model but with achievable error rates smaller than the local model. In this paper, we study pure differentially private protocols in the shuffled model for summation, a very basic and widely used primitive. Specifically: - For the binary summation problem where each of n users holds a bit as an input, we give a pure ε-differentially private protocol for estimating the number of ones held by the users up to an absolute error of O_{ε}(1), and where each user sends O_{ε}(log n) one-bit messages. This is the first pure protocol in the shuffled model with error o(√n) for constant values of ε. Using our binary summation protocol as a building block, we give a pure ε-differentially private protocol that performs summation of real numbers in [0, 1] up to an absolute error of O_{ε}(1), and where each user sends O_{ε}(log³ n) messages each consisting of O(log log n) bits. - In contrast, we show that for any pure ε-differentially private protocol for binary summation in the shuffled model having absolute error n^{0.5-Ω(1)}, the per user communication has to be at least Ω_{ε}(√{log n}) bits. This implies (i) the first separation between the (bounded-communication) multi-message shuffled model and the central model, and (ii) the first separation between pure and approximate differentially private protocols in the shuffled model. Interestingly, over the course of proving our lower bound, we have to consider (a generalization of) the following question that might be of independent interest: given γ ∈ (0, 1), what is the smallest positive integer m for which there exist two random variables X⁰ and X^1 supported on {0, … , m} such that (i) the total variation distance between X⁰ and X^1 is at least 1 - γ, and (ii) the moment generating functions of X⁰ and X^1 are within a constant factor of each other everywhere? We show that the answer to this question is m = Θ(√{log(1/γ)})., LIPIcs, Vol. 163, 1st Conference on Information-Theoretic Cryptography (ITC 2020), pages 15:1-15:23

ObjectiveCentral sensitization is present in different pain conditions, including chronic whiplash-associated disorders. In the absence of a gold standard method of assessment to determine the presence of central sensitization, quantitative sensory testing is currently understood as an optimal proxy. Laboratory sensory testing is, however, not feasible in clinical practice, and the Central Sensitization Inventory was developed as an alternative. The aim of the current study was to evaluate the convergent validity of the Central Sensitization Inventory in chronic whiplash-associated patients by determining the association between the Central Sensitization Inventory and quantitative sensory testing, pain intensity, fatigue, and psychosocial factors.MethodsA total of 125 chronic whiplash-associated patients completed multiple questionnaires and were subjected to pressure pain thresholds and temporal summation.Results. The Central Sensitization Inventory showed a strong association with constructs of general psychopathology, anxiety, distress, depression, and somatization in chronic whiplash-associated disorders. Moderate correlations were found with fatigue and intrusive and avoidant phenomena after a variety of traumatic events. No significant association was found between the Central Sensitization Inventory and pressure pain thresholds and temporal summation, nor between the Central Sensitization Inventory and other pain measurements.ConclusionsOverall, we found that the Central Sensitization Inventory is better in identifying the psychosocial factors related to central sensitization in chronic whiplash-associated disorders than the central nervous system adaptations. Thus, the convergent validity of the Central Sensitization Inventory appears to be only partially present in chronic whiplash-associated disorders.