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Background: There is conflicting evidence on how central processing impairments affect patients with temporomandibular disorders (TMD). Moreover, there is sparse research on the assessment of endogenous pain modulation in this population through conditioned pain modulation (CPM) testing. Objective(s): The main objective of this observational study was to evaluate the possible differences between myofascial TDM patients and healthy pain-free controls on psychophysical variables suggestive of central processing impairments (including temporal summation (TSP), pressure pain threshold (PPT) and conditioned pain modulation (CPM)). Methods: This is a cross-sectional observational study including a sample of patients with TMD and pain-free controls recruited from private and university clinics in Spain. Outcome measures included local and distal PPTs, temporal summation, conditioned pain modulation and psychological factors of depression, anxiety, kinesiophobia, fear avoidance beliefs and pain catastrophizing. Results: Fifty-nine patients with TMD of myofascial origin (32 years [IR: 25–43]) and 30 healthy, pain-free controls (29.5 years [IR: 25–41]) participated in the study and completed the evaluations. Patients with TMD showed significantly reduced CPM (p = 0.001; t = 3.31) and both local and distal PPTs (p < 0.05) when compared with controls, after adjusting for the influence of age and sex. TSP did not show any difference between the groups (p = 0.839; Z = 0.20). All psychological factors were higher in patients with TMD (p < 0.005), except for anxiety (p = 0.134). Conclusion: Patients with myofascial TMD included in this study exhibited signs of altered central processing, linked to impaired descending pain modulation, distal hyperalgesia and psychological factors like depression, kinesiophobia, fear avoidance beliefs and pain catastrophizing but not anxiety. [ABSTRACT FROM AUTHOR]

Background: Patients with migraine are vulnerable to insufficient sleep, but the impact of sleep restriction is largely unknown. In addition, the importance of sleep may be different in patients with migraine who mostly have attack onsets during sleep, so called sleep-related migraine, compared to patients with non-sleep-related migraine. In this study we investigate the effect of sleep restriction on endogenous pain modulation in patients with migraine and healthy controls. We also compared the effect of sleep restriction in sleep-related and in non-sleep-related migraine. Methods: Measurements were conducted in 39 patients with migraine between attacks and 31 controls, once after habitual sleep and once after two consecutive nights of partial sleep restriction. There were 29 and 10 patients with non-sleep-related and sleep-related migraine respectively. Test stimulus was 2-min tonic noxious heat to the left volar forearm. Temporal summation was calculated as the regression coefficient for rated pain in the late part of this 2-min stimulation. Conditioning stimulus was right hand-immersion in 7 °C water. Conditioned pain modulation was defined as the difference in rated pain with and without the conditioning stimulus and was calculated for temporal summation and mean rated pain for the test stimulus. The effect of sleep restriction on temporal summation and conditioned pain modulation was compared in migraine subjects and controls using two-level models with recordings nested in subjects. Results: Conditioned pain modulation for temporal summation of heat pain tended to be reduced after sleep restriction in patients with migraine compared to controls (p = 0.060) and, in an exploratory analysis, was reduced more after sleep restriction in sleep-related than in non-sleep-related migraine (p = 0.017). No other differences between groups after sleep restriction were found for temporal summation or conditioned pain modulation. Conclusion: Patients with migraine may have a subtly altered endogenous pain modulation system. Sleep restriction may have an increased pronociceptive effect on this system, suggesting a mechanism for vulnerability to insufficient sleep in migraine. This effect seems to be larger in sleep-related migraine than in non-sleep-related migraine. [ABSTRACT FROM AUTHOR]

Researchers have been focusing on perceptual characteristics of autism spectrum disorder (ASD) in terms of sensory hyperreactivity. Previously, we demonstrated that temporal resolution, which is the accuracy to differentiate the order of two successive vibrotactile stimuli, is associated with the severity of sensory hyperreactivity. We currently examined whether an increase in the perceptual intensity of a tactile stimulus, despite its short duration, is derived from high temporal resolution and high frequency of sensory temporal summation. Twenty ASD and 22 typically developing (TD) participants conducted two psychophysical experimental tasks to evaluate detectable duration of vibrotactile stimulus with same amplitude and to evaluate temporal resolution. The sensory hyperreactivity was estimated using self-reported questionnaire. There was no relationship between the temporal resolution and the duration of detectable stimuli in both groups. However, the ASD group showed severe sensory hyperreactivity in daily life than TD group, and the ASD participants with severe sensory hyperreactivity tended to have high temporal resolution, not high sensitivity of detectable duration. Contrary to the hypothesis, there might be different processing between temporal resolution and sensitivity for stimulus detection. We suggested that the atypical temporal processing would affect to sensory reactivity in ASD. [ABSTRACT FROM AUTHOR]

Conditioned pain modulation (CPM) and temporal summation (TS) tests can measure the ability to inhibit pain in fibromyalgia syndrome (FMS) patients and its level of pain sensitization, respectively. However, their clinical validity is still unclear. We studied the association between changes in the CPM and TS tests and the clinical improvement of FMS patients who received therapeutic intervention. We systematically searched for FMS randomized clinical trials with data on therapeutic interventions comparing clinical improvement (pain intensity and symptom severity reduction), CPM, and TS changes relative to control interventions. To study the relationship between TS/CPM and clinical measures, we performed a meta-regression analysis to calculate odds ratios. We included nine studies (484 participants). We found no significant changes in TS or CPM by studying all the interventions together. Our findings show that this lack of difference is likely because pharmacological and non-pharmacological interventions resulted in contrary effects. Non-pharmacological interventions, such as non-invasive neuromodulation, showed the largest effects normalizing CPM/TS. Meta-regression was significantly associated with pain reduction and symptom severity improvement with normalization of TS and CPM. We demonstrate an association between clinical improvement and TS/CPM normalization in FMS patients. Thus, the TS and CPM tests could be surrogate biomarkers in FMS management. Recovering defective endogenous pain modulation mechanisms by targeted non-pharmacological interventions may help establish long-term clinical recovery in FMS patients. [ABSTRACT FROM AUTHOR]

Abstract Background Patients with migraine are vulnerable to insufficient sleep, but the impact of sleep restriction is largely unknown. In addition, the importance of sleep may be different in patients with migraine who mostly have attack onsets during sleep, so called sleep-related migraine, compared to patients with non-sleep-related migraine. In this study we investigate the effect of sleep restriction on endogenous pain modulation in patients with migraine and healthy controls. We also compared the effect of sleep restriction in sleep-related and in non-sleep-related migraine. Methods Measurements were conducted in 39 patients with migraine between attacks and 31 controls, once after habitual sleep and once after two consecutive nights of partial sleep restriction. There were 29 and 10 patients with non-sleep-related and sleep-related migraine respectively. Test stimulus was 2-min tonic noxious heat to the left volar forearm. Temporal summation was calculated as the regression coefficient for rated pain in the late part of this 2-min stimulation. Conditioning stimulus was right hand-immersion in 7 °C water. Conditioned pain modulation was defined as the difference in rated pain with and without the conditioning stimulus and was calculated for temporal summation and mean rated pain for the test stimulus. The effect of sleep restriction on temporal summation and conditioned pain modulation was compared in migraine subjects and controls using two-level models with recordings nested in subjects. Results Conditioned pain modulation for temporal summation of heat pain tended to be reduced after sleep restriction in patients with migraine compared to controls (p = 0.060) and, in an exploratory analysis, was reduced more after sleep restriction in sleep-related than in non-sleep-related migraine (p = 0.017). No other differences between groups after sleep restriction were found for temporal summation or conditioned pain modulation. Conclusion Patients with migraine may have a subtly altered endogenous pain modulation system. Sleep restriction may have an increased pronociceptive effect on this system, suggesting a mechanism for vulnerability to insufficient sleep in migraine. This effect seems to be larger in sleep-related migraine than in non-sleep-related migraine.

Summary Acute sleep deprivation in experimental studies has been shown to induce pain hypersensitivity in females. However, the impact of natural sleep deficiency and fluctuations across the week on pain perception remains unclear. A sleep‐monitoring headband and self‐reports were utilized to assess objective and subjective sleep in longer (> 6 hr) and short sleepers (< 6 hr). Pain sensitivity measures including heat, cold, pressure pain thresholds, pain inhibition (conditioned pain modulation) and facilitation (tonic pain summation) were assessed on Mondays and Fridays. Forty‐one healthy young (23.9 ± 0.74 years) women participated. Short sleepers slept on average 2 hr less than longer sleepers (297.9 ± 8.2 min versus 418.5 ± 10.9 min) and experienced impaired pain inhibitory response (mean = −21.14 ± 7.9°C versus mean = 15.39 ± 9.5°C; p = 0.005). However, no effect was observed in pain thresholds and pain summation (p > 0.05). Furthermore, pain modulatory responses differed between Mondays and Fridays. Chronic sleep deficiency (< 6 hr) compromises pain responses, notably on Mondays. Maintaining a consistent sleep pattern with sufficient sleep (> 6 hr) throughout the week may protect against pain sensitization and the development of chronic pain in females. Further research is needed, especially in patients with chronic pain. [ABSTRACT FROM AUTHOR]

The foveated architecture of the human retina and the eye’s mobility enables prime spatial vision, yet the interplay between photoreceptor cell topography and the constant motion of the eye during fixation remains unexplored. With in vivo foveal cone-resolved imaging and simultaneous microscopic photo stimulation, we examined visual acuity in both eyes of 16 participants while precisely recording the stimulus path on the retina. We find that resolution thresholds were correlated with the individual retina’s sampling capacity, and exceeded what static sampling limits would predict by 18%, on average. The length and direction of fixational drift motion, previously thought to be primarily random, played a key role in achieving this sub-cone diameter resolution. The oculomotor system finely adjusts drift behavior towards retinal areas with higher cone densities within only a few hundred milliseconds to enhance retinal sampling.

Parker A Kell,1 Claudia N Vore,1 Burkhart J Hahn,1,2 Michael F Payne,1,3 Jamie L Rhudy1 1Department of Psychology, The University of Tulsa, Tulsa, OK, USA; 2Department of Psychology, Oklahoma State University, Stillwater, OK, USA; 3Department of Pediatrics, Division of Child & Adolescent Psychiatry, Cincinnati Children’s Hospital Medical Center, Cincinnati, OH, USACorrespondence: Jamie L Rhudy, University of Oklahoma Health Sciences Center, TSET Health Promotion Research Center, Department of Health Promotion Sciences, 4502 E. 41st Street, Tulsa, OK, 74104, USA, Tel +1 918-660-3050, Email jamie-rhudy@ouhsc.eduPurpose: Temporal summation (TS) of pain occurs when pain increases over repeated presentations of identical noxious stimuli. TS paradigms can model central sensitization, a state of hyperexcitability in nociceptive pathways that promotes chronic pain onset and maintenance. Many experimenters use painful heat stimuli to measure TS (TS-heat); yet, TS-heat research faces unresolved challenges, including difficulty evoking summation in up to 30– 50% of participants. Moreover, substantial variability exists between laboratories regarding the methods for evoking and calculating TS-heat.Patients and Methods: To address these limitations, this study sought to identify optimal parameters for evoking TS-heat in healthy participants with a commercially available constant contact heat stimulator, the Medoc TSA-II. Working within constraints of the TSA-II, stimulus trains with varying parameters (eg, stimulus frequency, baseline temp, peak temp, peak duration, testing site) were tested in a sample of 32 healthy, chronic pain-free participants to determine which combination best evoked TS-heat. To determine whether TS scoring method altered results, TS-heat was scored using three common methods.Results: Across all methods, only two trains successfully evoked group-level TS-heat. These trains shared the following parameters: site (palmar hand), baseline and peak temperatures (44°C and 50°C, respectively), and peak duration (0.5 s). Both produced summation that peaked at moderate pain (~50 out of 100 rating).Conclusion: Future TS-heat investigations using constant contact thermodes and fixed protocols may benefit from adopting stimulus parameters that include testing on the palmar hand, using 44°C baseline and 50°C peak temperatures, at ≥ 0.33 Hz stimulus frequency, and peak pulse durations of at least 0.5 seconds.Keywords: temporal summation, heat pain, second pain, wind-up, Medoc TSA-II

Conditioned pain modulation (CPM) and temporal summation (TS) tests can measure the ability to inhibit pain in fibromyalgia syndrome (FMS) patients and its level of pain sensitization, respectively. However, their clinical validity is still unclear. We studied the association between changes in the CPM and TS tests and the clinical improvement of FMS patients who received therapeutic intervention. We systematically searched for FMS randomized clinical trials with data on therapeutic interventions comparing clinical improvement (pain intensity and symptom severity reduction), CPM, and TS changes relative to control interventions. To study the relationship between TS/CPM and clinical measures, we performed a meta-regression analysis to calculate odds ratios. We included nine studies (484 participants). We found no significant changes in TS or CPM by studying all the interventions together. Our findings show that this lack of difference is likely because pharmacological and non-pharmacological interventions resulted in contrary effects. Non-pharmacological interventions, such as non-invasive neuromodulation, showed the largest effects normalizing CPM/TS. Meta-regression was significantly associated with pain reduction and symptom severity improvement with normalization of TS and CPM. We demonstrate an association between clinical improvement and TS/CPM normalization in FMS patients. Thus, the TS and CPM tests could be surrogate biomarkers in FMS management. Recovering defective endogenous pain modulation mechanisms by targeted non-pharmacological interventions may help establish long-term clinical recovery in FMS patients.

Cluster Headache (CH) is a primary headache that causes severe pain. Some evidence suggests that central mechanisms might be involved. The objective of this study was (1) to compare hyperalgesia signs, temporal summation and conditioned pain modulation among episodic (ECH) and chronic CH (CCH) patients and controls, (2) to compare these factors between sides in the patient groups and (3) to compare the psychophysical variables between the groups. This cross-sectional study included 71 subjects divided into three groups (ECH, CCH and controls). Pressure pain thresholds, temporal summation, conditioned pain modulation and other psychosocial variables were measured. The ANOVA showed differences for all physical outcome measures (p < 0.05). Bonferroni post hoc analyses showed differences when comparing the patient groups with the healthy subjects (p < 0.05), with large effect sizes (d > 0.8). No differences between the patient groups were found for almost all the variables (p > 0.05). Significant differences for all the variables were detected when comparing the symptomatic and non-symptomatic sides in both the ECH and CCH groups (p < 0.05). The ECH and CCH groups showed mechanical hyperalgesia, increased temporal summation and impaired inhibitory mechanisms compared to the controls. Side-to-side differences were also detected within the patient groups. Patients with CCH had poorer sleep quality and quality of life than the controls. [ABSTRACT FROM AUTHOR]

Cluster Headache (CH) is a primary headache that causes severe pain. Some evidence suggests that central mechanisms might be involved. The objective of this study was (1) to compare hyperalgesia signs, temporal summation and conditioned pain modulation among episodic (ECH) and chronic CH (CCH) patients and controls, (2) to compare these factors between sides in the patient groups and (3) to compare the psychophysical variables between the groups. This cross-sectional study included 71 subjects divided into three groups (ECH, CCH and controls). Pressure pain thresholds, temporal summation, conditioned pain modulation and other psychosocial variables were measured. The ANOVA showed differences for all physical outcome measures (p < 0.05). Bonferroni post hoc analyses showed differences when comparing the patient groups with the healthy subjects (p < 0.05), with large effect sizes (d > 0.8). No differences between the patient groups were found for almost all the variables (p > 0.05). Significant differences for all the variables were detected when comparing the symptomatic and non-symptomatic sides in both the ECH and CCH groups (p < 0.05). The ECH and CCH groups showed mechanical hyperalgesia, increased temporal summation and impaired inhibitory mechanisms compared to the controls. Side-to-side differences were also detected within the patient groups. Patients with CCH had poorer sleep quality and quality of life than the controls.

The foveated architecture of the human retina and the eye's mobility enables prime spatial vision, yet the interplay between photoreceptor cell topography and the constant motion of the eye during fixation remains unexplored. With in vivo foveal cone-resolved imaging and simultaneous microscopic photo stimulation, we examined visual acuity in both eyes of 16 participants while precisely recording the stimulus path on the retina. We find that resolution thresholds were correlated with the individual retina's sampling capacity, and exceeded what static sampling limits would predict by 18%, on average. The length and direction of fixational drift motion, previously thought to be primarily random, played a key role in achieving this sub-cone diameter resolution. The oculomotor system finely adjusts drift behavior towards retinal areas with higher cone densities within only a few hundred milliseconds to enhance retinal sampling., Competing Interests: JW, VL, WH No competing interests declared, (© 2024, Witten et al.)

Fibromyalgia (FM) is a common chronic pain condition for which acupuncture treatment is increasingly utilized. However, there is no universally accepted measure to predict whether a specific patient will benefit from acupuncture. This is a single-center, single-blind, sham-controlled, randomized, noncrossover, longitudinal trial of 76 subjects with FM, assigned to either electroacupuncture (EA) or a placebo control, mock laser (ML) acupuncture. Outcome measures included clinical pain severity (Brief Pain Inventory [BPI]), degree of nociplastic pain (Fibromyalgia Survey Questionnaire), and pressure pain tolerance (PPtol). Baseline measures of temporal summation of pain and expectations for treatment relief were used as predictors. Individuals in both treatment groups experienced significant reductions in BPI (EA: P < .001, ML: P = .018) and Fibromyalgia Survey Questionnaire (EA: P = .032, ML: P = .002) after treatment; however, neither group showed a significant increase in PPtol. Lower temporal summation at baseline was correlated with greater post-treatment improvement in BPI in the EA group (rho = .389, P = .025) but not in the ML group (rho = -.272, P = .109). Lower-baseline temporal summation was correlated with greater decreases in PPtol following EA (rho = .400, P = .040), whereas the opposite was seen for ML (rho = -.562, P = .001). Treatment expectancy at baseline was not correlated with any outcome after EA or ML treatments. Our results support using a quantitative sensory testing metric, temporal summation of pain, but not expectations, to predict analgesia following acupuncture treatment for pain. PERSPECTIVE: A randomized study of acupuncture in FM found baseline temporal summation, but not expectations of pain relief, to be predictive of treatment response. CLINICAL TRIAL REGISTRATION: Registered under ClinicalTrials.gov identifier NCT02064296., (Copyright © 2024. Published by Elsevier Inc.)

Context: Patellofemoral pain (PFP) has poor long-term recovery outcomes. Central sensitization describes central nervous system changes altering pain modulation, which can complicate recovery (poorer prognosis, worse function). Signs of central sensitization include amplified pain facilitation, pain hypersensitivity, and impaired pain inhibition, which can be measured with temporal summation of pain (TSP), pressure pain thresholds (PPTs) and conditioned pain modulation (CPM), respectively. Sex differences exist for these test responses, but female-only PFP investigations of sensitization are uncommon. Understanding pain modulation in females with PFP could improve treatment protocols., Objective: To determine whether females with PFP exhibit signs of central sensitization (greater TSP, lower PPTs, reduced CPM) compared to pain-free females., Design: Cross-sectional Setting: Laboratory Patients or Other Participants: Thirty-three females [(20 PFP, 13 pain-free); Age: PFP 29.2 ± 7 years, pain-free 28 ± 7 years; Height: PFP 166.7 ± 5.9cm, pain-free 166 ± 9.5cm, Mass: PFP 66.7 ± 9.6kg, pain-free 69.3 ± 7.5kg)., Main Outcome Measures: TSP was assessed with ten punctate stimuli applied to the knee and calculated by the difference in pain intensity between beginning and end responses. PPTs were tested at four sites [3 for local hypersensitivity (knee), 1 for widespread hypersensitivity (hand)]. CPM was conducted by comparing PPTs during two conditions (baseline, ice immersion). CPM response was defined as the percent difference between conditions. Between-group differences in TSP response were analyzed with a Welch's test. Separate Welch's tests analyzed group comparisons of PPTs and CPM responses at four sites., Results: Females with PFP exhibited greater TSP response (P=0.019) and lower CPM response at patella center (P=0.010) and hand sites (P=0.007) than pain-free females. PPT group differences were not observed at any site (P>0.0125)., Conclusions: Females with PFP modulate pain differently than pain-free females. Clinicians should recognize signs of central sensitization and their potential impact on treatment options.

Central sensitization (CS) involves an amplification of neural processing within the central nervous system that can result in widespread pain patterns and hypersensitivity to stimuli. The Central Sensitization Inventory (CSI) and various quantitative sensory testing (QST) methods purport to assess clinical markers of CS. The purpose of this systematic review and meta-analysis was to summarize and quantify the associations between total CSI scores and QST measures from previous studies. A systematic search identified 39 unique studies that were deemed eligible for the systematic review and 33 studies for meta-analyses (with 3314 subjects and 154 effect sizes), including five QST modalities: conditioned pain modulation, temporal summation, pressure pain threshold, heat pain threshold, and cold pain threshold. The meta-analysis yielded statistically significant CSI-QST correlations in total subject samples for all five QST modalities. The strongest associations were identified between CSI scores and pain threshold testing, especially pressure pain threshold, in which 51% of effects sizes, from 29 studies and 3071 subjects, were determined to be in a medium to large range. • Significant correlations were found between CSI total scores and five separate QST modalities. • The strongest association was found between CSI total scores and pressure pain threshold testing. • Knee osteoarthritis had the strongest CSI and pressure pain threshold relationship. • No CSI and pressure pain threshold relationship was found in healthy control subjects. [ABSTRACT FROM AUTHOR]