Showing papers on "Summation published in 2023"

Spatiotemporal summation of perimetric stimuli in healthy observers

Abstract: Spatial summation of perimetric stimuli has been used to derive conclusions about the spatial extent of retinal-cortical convergence, mostly from the size of the critical area of summation (Ricco’s area, RA) and critical number of Retinal Ganglion Cells (RGCs). However, spatial summation is known to change dynamically with stimulus duration. Conversely, temporal summation and critical duration also vary with stimulus size. Such an important and often neglected spatio-temporal interaction has important implications for modelling perimetric sensitivity in healthy observers and for formulating hypotheses for changes measured in disease. In this work, we performed experiments on visually heathy observers confirming the interaction of stimulus size and duration in determining summation responses in photopic conditions. We then propose a simplified computational model that captures these aspects of perimetric sensitivity by modelling the total retinal input, the combined effect of stimulus size, duration and retinal cones-to-RGC ratio. We additionally show that, in the macula, the enlargement of RA with eccentricity might not correspond to a constant critical number of RGCs, as often reported, but to a constant critical total retinal input. We finally compare our results with previous literature and show possible implications for modelling disease, especially glaucoma.

Central sensitization in CRPS patients with widespread pain: A cross-sectional study.

Abstract: OBJECTIVE Widespread pain hypersensitivity and enhanced temporal summation of pain (TSP) are commonly reported in patients with complex regional pain syndrome (CRPS) and discussed as proxies for central sensitization. This study aimed to directly relate such signs of neuronal hyperexcitability to the pain phenotype of CRPS patients. METHODS Twenty-one CRPS patients and 20 healthy controls (HC) were recruited. The pain phenotype including spatial pain extent (assessed in % body surface) and intensity were assessed and related to widespread pain hypersensitivity, TSP, and psychological factors. Quantitative sensory testing (QST) was performed in the affected, the contralateral and a remote (control) area. RESULTS CRPS patients showed decreased pressure pain thresholds in all tested areas (affected: t(34)=4.98, p < 0.001, contralateral: t(35)=3.19, p = 0.005, control: t(31)=2.65, p = 0.012). Additionally, patients showed increased TSP in the affected area (F(3,111)=4.57, p = 0.009) compared to HC. TSP was even more enhanced in patients with a high compared to a low spatial pain extent (F(3,51)=5.67, p = 0.008), suggesting pronounced spinal sensitization in patients with extended pain patterns. Furthermore, the spatial pain extent positively correlated with the Bath Body Perception Disturbance Scale (ρ = 0.491; p = 0.048). CONCLUSION Overall, we provide evidence that the pain phenotype in CRPS, i.e., spatial pain extent, might be related to sensitization mechanism within the central nociceptive system. This study points towards central neuronal excitability as a potential therapeutic target in patients with more widespread CRPS.

Sex differences in pain and quantitative sensory testing in patients with rheumatoid arthritis.

Abstract: OBJECTIVE Women with rheumatoid arthritis (RA) have higher pain and worse functional outcomes compared to men, even when treated with similar medications. The objective of this study was to identify sex differences in pain intensity, pain interference and quantitative sensory tests (QST), which are independent of inflammation, in patients with RA. METHODS This study is a post hoc analysis of participants in the Central Pain in Rheumatoid Arthritis (CPIRA) cohort. Pain intensity was assessed using a 0-10 numeric rating scale. Pain interference was measured using a Patient-Reported Outcomes Measurement Information System (PROMIS) computerized adaptive test. QST included pressure pain detection thresholds, temporal summation, and conditioned pain modulation. Women and men were compared using multiple linear regression, adjusted for age, education, race, research site, depression, obesity, RA disease duration, swollen joint count (SJC), and C-reactive protein (CRP). RESULTS Mean pain intensity was 5.32 ± 2.29 among women with RA, compared to 4.60 ± 2.23 among men with RA (adjusted difference 0.83, 95% CI 0.14, 1.53). Women with RA had lower pressure pain detection thresholds at the trapezius (adjusted difference -1.22, 95% CI -1.73, -0.72), wrist (adjusted difference -0.57, 95% CI -1.07, -0.06), and knee (adjusted difference -1.10, 95% CI -2.00, -0.21). No statistically significant differences in pain interference, temporal summation, and conditioned pain modulation were observed. CONCLUSIONS Women reported higher pain intensity and lower pressure pain detection thresholds (higher pain sensitivity) than men. However, pain interference, temporal summation, and conditioned pain modulation did not differ between men and women.

Exploration of Somatosensory Function of Patients with Acute Non-specific Neck Pain, Through Quantitative Sensory Testing and Self-reported Symptoms

Abstract: Adaptations in somatosensory function characterize several chronic pain conditions, including non-specific neck pain (NNP). Early signs of central sensitization (CS) contribute to pain chronification and poor treatment responses after e.g. whiplash injury and low back pain. Despite this well-established association, the prevalence of CS in patients with acute NNP, and accordingly the potential impact of this association, is still unclear. Therefore, this study aims to investigate whether changes in somatosensory function occur during the acute phase of NNP.This cross-sectional study compared 35 patients with acute NNP, with 27 pain-free individuals. All participants completed standardized questionnaires and an extensive multimodal Quantitative Sensory Testing protocol. A secondary comparison was made with 60 patients with chronic WAD, a population wherein CS is well-established.Compared to pain-free individuals, pressure pain thresholds (PPTs) at remote areas and thermal detection and pain thresholds were unaltered. However, patients with acute NNP showed lower cervical PPTs and conditioned pain modulation, and higher temporal summation, Central Sensitization Index (CSI) scores, and pain intensity. Compared to the group with chronic WAD, PPTs did not differ at any location, yet CSI scores were lower.Changes in somatosensory function occur already in acute NNP. Local mechanical hyperalgesia demonstrated peripheral sensitization, while enhanced pain facilitation, impaired conditioned pain modulation, and self-reported symptoms of CS suggest adaptations in pain processing already early in the stage of NNP.

The periaqueductal grey in chronic low back pain: dysregulated metabolites and function

Abstract: Mechanisms underlying chronic pain are insufficiently understood. Preclinical evidence suggests a potential contribution of excitatory glutamatergic and inhibitory GABAergic imbalances in pain-relevant brain areas, such as a lower excitatory/inhibitory tone in the brainstem periaqueductal grey (PAG). This cross-sectional magnetic resonance spectroscopy (MRS) study investigated whether a lower excitatory/inhibitory tone is also observed in the PAG of patients with non-specific chronic low back pain (CLBP) and whether this would relate to altered psychophysical measures of descending pain modulation and experimental pressure pain sensitivity. Specifically, the ratio between pooled glutamate and glutamine and GABA levels (Glx/GABA), Glx and GABA in the PAG were compared between CLBP patients and pain-free controls. Further, associations of Glx/GABA with conditioned pain modulation (CPM) effects and pressure pain thresholds (PPTs) were assessed. MRS was acquired on a 3T Philipps MR system using a point-resolved spectroscopy sequence optimized with very selective saturation pulses (OVERPRESS) and voxel-based flip angle calibration in a 1.1 mL volume of interest. Data from 41 CLBP patients (median [interquartile range]: 54 years [41 - 65], 22 females) and 29 age- and sex-matched controls (47 years [34 - 67], 17 females) fulfilled MRS quality criteria. CPM and PPTs were assessed at the lower back as most painful area and the non-dominant hand as pain-free control area. The CPM paradigm consisted of PPTs applied before, during (parallel CPM effect) and after a cold water bath and an ambient temperature water bath as control paradigm to identify 'true' CPM effects. In the PAG of CLBP patients, a lower Glx/GABA ratio, i.e. a lower excitatory/inhibitory tone, was observed (P = 0.002, partial {eta}2 = 0.14) driven by decreased Glx (P = 0.012, partial {eta}2 = 0.11) and increased GABA (P = 0.038, d = 0.46). CLBP patients showed disrupted associations between Glx/GABA and PPTs compared to controls in both areas (lower back: P = 0.004, partial {eta}2 = 0.12; hand: P = 0.002, partial {eta}2 = 0.16). In controls, lower Glx/GABA was associated with lower PPTs (lower back: r = 0.48, P = 0.009, hand: r = 0.53, P = 0.003), but this link was missing in CLBP patients (r's > -0.23, P's > 0.150). Additionally, CLBP patients with more severe clinical pain showed smaller CPM effects at the hand (rho = 0.54, P = 0.003). These findings suggest a dysfunction of the PAG in patients with CLBP and might indicate altered descending inhibition of deep tissue afferents.

Pos0365 sex differences concerning experienced pain in patients with axial spondyloarthritis

Abstract: Research shows that there are significant sex differences in experienced pain. Contributing factors are neuroanatomical, hormonal, neuroimmunological, psychological, social, cultural, and comorbidities. Women have more and different expression of nociceptors, and a stronger proinflammatory response to tissue damage than men. Women also use different coping styles regarding to pain and tend to engage more in pain catastrophizing. Therefore, women may experiencing more severe pain than men. Also in axial spondyloarthritis (axSpA), higher pain scores are observed in women compared to men with axSpA.[1] Sex differences in experienced pain within axSpA is not well studied. It is unclear if differences are related to the involvement of altered pain processing of the central nervous system (CNS) including central sensitization (CS) and/or psycho-social aspects.To explore sex differences in pain perception, coping with pain, pain catastrophizing and altered pain processing of the CNS in patients with axSpA.A cross-sectional study of consecutive outpatients from the Groningen Leeuwarden axSpA (GLAS) cohort, fulfilling the ASAS classification criteria. Participants filled out the Central Sensitization Inventory (CSI), Pain Catastrophizing Scale (PCS) Coping with Rheumatic Stressors (CORS), and underwent Quantitative Sensory Testing (QST) according to a standardized protocol, including Pain Threshold Testing (PTT) at 11 sites, Temporal Summation (TS) at 3 sites and Conditioned Pain Modulation (CPM). Widespread low PPTs, high TS (both pain facilitation) and positive CPM (impaired pain inhibition) are indicators of CS. Independent Samples T Test and Mann-Whitney U Test were used for normally- and non-normally distributed data resp.. Bonferroni correction was applied for multiple significance testing and P-value was determined at 0.004.201 patients were included, 128 men and 73 women with no significant differences in the patient characteristics; median age (50.8 vs 51.6 years), median symptom duration (22.0 vs 21.0 years) and median CRP (1.8 vs 2.5). Significant differences between men and women were observed for the classification radiographic axSpA (71.9% vs 50.7%), HLA-B27 status (84.1% vs 67.1%), mean BMI (27.2 ± 4.9 vs 29.0 ± 6.9), mean ASDASCRP(2.1 ± 0.8 vs 2.5 ± 0.9) and mean BASDAI (3.4 ± 2.1 vs 4.7 ± 2.1). Women scored significantly higher on the CSI and used the coping styles comforting cognitions, decreased activities and diverted attention more often (CORS). Concerning the involvement of altered pain processing of the CNS, women had significantly lower PPTs. TS and CPM were comparable in men and women (Table 1).In patients with axSpA, significant sex differences in pain coping styles, CSI score and PPTs were observed. Therefore, sex differences should be taken into account in the management of pain in daily clinical practice and in pain research in these patients.[1]Rusman et al. Rheumatology 2020Table 1.Characteristics and assessments stratified for sex (n=201)Men (n=128)Women (n=73)CSI-A (0-100)30.6 ± 13.841.5 ± 13.6*PCS (0-52)11.0 [5.0-20.0]14.0 [5.0-19.5]CORS pain Comforting cognitions27.8 ± 4.929.9 ± 4.1* Decreasing activities18.8 ± 4.521.0 ± 4.3*Diverting attention20.1 ± 4.722.3 ± 3.9*PPT (N)Thenar, left/right37.4 ±17.5/40.6 ± 19.126.1 ± 12.1/29.0 ±14.2*M. trapezius, left/right40.1 ± 22.8/39.4 ± 20.926.8 ± 13.5/26.8 ± 14.5*M. rectus femoris, left/right58.0 ± 25.1/55.9 ± 26.835.2 ± 17.9/32.1 ± 16.3*M. abductor hallucis, left/right37.0 ± 18.4/38.6 ± 19.827.5 ± 13.2/28.7 ± 15.1* Non-painful area38.6 ± 22.125.0 ± 13.8* Painful area32.2 [22.4-51.6]19.8 [13.0-28.7]*TS (VAS)Non-dominant forearm0.6 [0.1-1.2]0.7 [0.2-2.1]Non-painful area0.8 [0.2-1.5]1.1 [0.2-2.2]Painful area0.8 [0.2-1.6]1.3 [0.3-2.7]CPM (N) Non-dominant m. rectus femoris2.8 ± 13.50.2 ± 8.3*Statistically significant at p<0.004 (Bonferroni correction).NIL.Yvonne van der Kraan: None declared, Davy Paap: None declared, Hans Timmerman: None declared, Freke Wink: None declared, Suzanne Arends: None declared, Michiel Reneman: None declared, Anneke Spoorenberg Grant/research support from: ReumaNederland Grant.

Perceptual learning based on a temporal stimulus enhances visual function in adult amblyopic subjects

Abstract: Studies have shown that Perceptual Learning (PL) can lead to enhancement of spatial visual functions in amblyopic subjects. Here we aimed to determine whether a simple flickering stimulus can be utilized in PL to enhance temporal function performance and whether enhancement will transfer to spatial functions in amblyopic subjects. Six adult amblyopic and six normally sighted subjects underwent an evaluation of their performance of baseline psychophysics spatial functions (Visual acuity (VA), contrast sensitivity (CS), temporal functions (critical fusion frequency (CFF) test), as well as a static and flickering stereopsis test, and an electrophysiological evaluation (VEP). The subjects then underwent 5 training sessions (on average, a total of 150 min over 2.5 weeks), which included a task similar to the CFF test using the method of constant stimuli. After completing the training sessions, subjects repeated the initial performance evaluation tasks. All amblyopic subjects showed improved temporal visual performance (CFF) in the amblyopic eye (on average, 17%, p << 0.01) following temporal PL. Generalization to spatial, spatio-temporal, and binocular tasks was also found: VA increased by 0.12 logMAR (p = 0.004), CS in backward masking significantly increased (by up to 19%, p = 0.003), and flickering stereopsis increased by 85 arcsec (p = 0.048). These results were further electrophysiologically manifested by an increase in VEP amplitude (by 43%, p = 0.03), increased Signal-to-Noise ratio (SNR) (by 39%, p = 0.024) to levels not different from normally sighted subjects, along with an improvement in inter-ocular delay (by 5.8 ms, p = 0.003). In contrast, no significant effect of training was found in the normally sighted group. These results highlight the potential of PL based on a temporal stimulus to improve the temporal and spatial visual performance in amblyopes. Future work is needed to optimize this method for clinical applications.

Responders and nonresponders to topical capsaicin display distinct temporal summation of pain profiles

Abstract: In Brief Introduction: Topical application of capsaicin can produce an ongoing pain state in healthy participants. However, approximately one-third report no pain response (ie, nonresponders), and the reasons for this are poorly understood. Objectives: In this study, we investigated temporal summation of pain (TSP) profiles, pain ratings and secondary hyperalgesia responses in responders and nonresponders to 1% topical capsaicin cream. Methods: Assessments were made at baseline and then during an early (ie, 15 minutes) and late (ie, 45 minutes) time points post-capsaicin in 37 healthy participants. Results: Participants reporting a visual analogue scale (VAS) rating of >50 were defined as responders (n = 24) and those with <50 VAS rating were defined as nonresponders (n = 13). There was a facilitation of TSP during the transition from an early to the late time point post-capsaicin (P<0.001) and the development of secondary hyperalgesia (P<0.05) in the responder group. Nonresponders showed no changes in TSP or secondary hyperalgesia during the early and late time points. There was an association between baseline TSP scores and the later development of a responder or nonresponder phenotype (r = 0.36; P = 0.03). Receiver operating characteristic analysis revealed that baseline TSP works as a good response predictor at an individual level (area under the curve = 0.75). Conclusion: These data suggest that responders and nonresponders have different facilitatory pain mechanisms. The assessment of TSP may help to identify participants with stronger endogenous pain facilitation who may be more likely to respond to topical capsaicin. Responders and nonresponders to topical capsaicin have different central facilitatory pain mechanisms.