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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]

African Americans are disproportionately exposed to adversity across the lifespan, which includes both stressful and traumatic events. Adversity, in turn, is associated with alterations in pain responsiveness. Racial differences in pain responsiveness among healthy adults are well established. However, the extent to which adversity type and timing are associated with alterations in pain responsiveness among healthy African-American adults is not well understood. The present study included 160 healthy African-American adults (98 women), ages 18 to 45. Outcome measures included pain tolerance and temporal summation of pain to evoked thermal pain. Composite scores were created for early-life adversity (childhood trauma, family adversity) and recent adversity (perceived stress, chronic stress burden). A measure of lifetime racial discrimination was also included. Higher levels of recent adversity were associated with higher temporal summation of pain, controlling for gender, age, and education. Neither early-life adversity nor lifetime racial discrimination were associated with temporal summation of pain. The present findings suggest that heightened temporal summation of pain among healthy African-American adults is associated with exposure to recent adversity events. Improved understanding of how recent adversity contributes to heightened temporal summation of pain in African Americans could help to mitigate racial disparities in pain experiences by identifying at-risk individuals who could benefit from early interventions. [ABSTRACT FROM AUTHOR]

Background: Population voltage imaging is used for studying brain physiology and brain circuits. Using a genetically encoded voltage indicator (GEVI), "VSFP" or "ASAP2s", or a voltage-sensitive dye, Di-4-Anepps, we conducted population voltage imaging in brain slices. The resulting optical signals, optical local field potentials (LFPs), were used to evaluate the performances of the 3 voltage indicators. Methods: In brain slices prepared from VSFP-transgenic or ASAP2s-transgenic mice, we performed multi-site optical imaging of evoked cortical depolarizations - compound excitatory postsynaptic potentials (cEPSPs). Optical signal amplitudes (ΔF/F) and cEPSP decay rates (OFF rates) were compared using analysis of variance (ANOVA) followed by unpaired Student's t test (31-104 data points per voltage indicator). Results: The ASAP2s signal amplitude (ΔF/F) was on average 3 times greater than Di-4-Anepps, and 7 times greater than VSFP. The optical cEPSP decay (OFF rate) was the slowest in Di-4-Anepps and fastest in ASAP2s. When ASAP2s expression was weak, we observed slow, label-free (autofluorescence, metabolic) optical signals mixed into the ASAP2s traces. Fast hyperpolarizations, that typically follow depolarizing cortical transients (afterhyperpolarizations), were prominent in ASAP2s but not present in the VSFP and Di-4-Anepps experiments. Conclusions: Experimental applications for ASAP2s may potentially include systems neuroscience studies that require voltage indicators with large signal amplitude (ΔF/F), fast decay times (fast response time is needed for monitoring high frequency brain oscillations), and/or detection of brain patches in transiently hyperpolarized states (afterhyperpolarization). [ABSTRACT FROM AUTHOR]

Introduction: In chronic pain conditions such as fibromyalgia (FM), pain amplification within the central nervous system, or "central sensitization," may contribute to the development and maintenance of chronic pain. Chronic pain treatments include opioid therapy, and opioid therapy may maladaptively increase central sensitization, particularly in patients who take opioids long-term. However, it has remained unknown how central sensitization is impacted in patients who use opioids long-term. Methods: To investigate how long-term opioid therapy affects central sensitization, we used the validated measure of temporal summation. The temporal summation measurement consists of applying a series of noxious stimuli to a patient's skin and then calculating changes in the patient's pain rating to each stimulus. Using this measurement, we evaluated temporal summation in study participants with fibromyalgia who take opioids long-term (i.e., greater than 90 days duration; n = 24, opioid-FM). We compared opioid-FM responses to 2 control groups: participants with fibromyalgia who do not take opioids (n = 33, non-opioid FM), and healthy controls (n = 31). For the temporal summation measurement, we applied a series of 10 noxious heat stimuli (sensitivity-adjusted temperatures) to the ventral forearm (2s duration of each stimulus, applied once every 3s). Additionally, we collected responses to standard pain and cognitive-affective questionnaires to assess pain severity and other factors. Results and discussion: Group differences in sensitivity-adjusted stimulus temperatures were observed, with only the non-opioid FM group requiring significantly lower stimulus temperatures (The opioid-FM group also required lower temperatures, but not significantly different from the control group). However, all 3 groups exhibited similar magnitudes of temporal summation. Across combined FM groups, temporal summation negatively correlated with pain severity (r = -0.31, p = 0.021). Within the opioid-FM group, higher pain sensitivity to heat (i.e., lower sensitivity-adjusted temperatures) showed a trend relationship with higher opioid dosage (r = -0.45, p = 0.036), potentially reflective of opioid-related hyperalgesia. Our findings also indicated that heightened pain severity may skew sensitivity-adjusted temporal summation, thereby limiting its utility for measuring central sensitization. Overall, in participants taking opioids, temporal summation may be influenced by hypersensitivity to heat pain, which appeared to vary with opioid dosage. [ABSTRACT FROM AUTHOR]

As humans age, the capacity of the central nervous system to endogenously modulate pain significantly deteriorates, thereby increasing the risk for the development of chronic pain. Older adults are the least physically active cohort of all age groups. We hypothesize that a sedentary lifestyle and decreased physical activity may contribute to the decline of endogenous pain modulation associated with aging. [ABSTRACT FROM AUTHOR]

Reading involves many different abilities that are necessary or sufficient conditions for fluent and flawless reading. The absence of one necessary or of all sufficient conditions is a cause of dyslexia. The present study investigates whether too short fixation times and an impaired ability to recognize a string of letters simultaneously are causes of dyslexia. The frequency and types of reading mistakes were investigated in a tachistoscopic pseudoword experiment with 100 children with dyslexia to test the impact of too short fixation times and the attempts of children with dyslexia to recognize more letters simultaneously than they can when reading pseudowords. The experiment demonstrates that all types of reading mistakes disappear when the fixation time increases and/or the number of letters that the children try to recognize simultaneously is reduced. The results cannot be interpreted as being due to altered visual crowding, impaired attention, or impaired phonological awareness, but can be regarded as an effect of impaired temporal summation and a dysfunction in the ventral stream of the visual system. [ABSTRACT FROM AUTHOR]

IntroductionIn chronic pain conditions such as fibromyalgia (FM), pain amplification within the central nervous system, or “central sensitization,” may contribute to the development and maintenance of chronic pain. Chronic pain treatments include opioid therapy, and opioid therapy may maladaptively increase central sensitization, particularly in patients who take opioids long-term. However, it has remained unknown how central sensitization is impacted in patients who use opioids long-term.MethodsTo investigate how long-term opioid therapy affects central sensitization, we used the validated measure of temporal summation. The temporal summation measurement consists of applying a series of noxious stimuli to a patient’s skin and then calculating changes in the patient’s pain rating to each stimulus. Using this measurement, we evaluated temporal summation in study participants with fibromyalgia who take opioids long-term (i.e., greater than 90 days duration; n = 24, opioid-FM). We compared opioid-FM responses to 2 control groups: participants with fibromyalgia who do not take opioids (n = 33, non-opioid FM), and healthy controls (n = 31). For the temporal summation measurement, we applied a series of 10 noxious heat stimuli (sensitivity-adjusted temperatures) to the ventral forearm (2s duration of each stimulus, applied once every 3 s). Additionally, we collected responses to standard pain and cognitive-affective questionnaires to assess pain severity and other factors.Results and discussionGroup differences in sensitivity-adjusted stimulus temperatures were observed, with only the non-opioid FM group requiring significantly lower stimulus temperatures (The opioid-FM group also required lower temperatures, but not significantly different from the control group). However, all 3 groups exhibited similar magnitudes of temporal summation. Across combined FM groups, temporal summation negatively correlated with pain severity (r = −0.31, p = 0.021). Within the opioid-FM group, higher pain sensitivity to heat (i.e., lower sensitivity-adjusted temperatures) showed a trend relationship with higher opioid dosage (r = −0.45, p = 0.036), potentially reflective of opioid-related hyperalgesia. Our findings also indicated that heightened pain severity may skew sensitivity-adjusted temporal summation, thereby limiting its utility for measuring central sensitization. Overall, in participants taking opioids, temporal summation may be influenced by hypersensitivity to heat pain, which appeared to vary with opioid dosage.

Knee osteoarthritis (OA) is a painful condition characterized by joint and bone changes. A growing number of studies suggest that these changes only partially explain the pain experienced by individuals with OA. The purpose of the current study was to evaluate if corticospinal and bulbospinal projection measurements were interrelated in patients with knee OA, and to explore the relationship between these neurophysiological measures and temporal summation (excitatory mechanisms of pain) on one hand, and clinical symptoms on the other. Twenty-eight (28) patients with knee OA were recruited. Corticospinal projections were measured using transcranial magnetic stimulation, while bulbospinal projections were evaluated with a conditioned pain modulation (CPM) protocol using a counter-irritation paradigm. Validated questionnaires were used to document clinical and psychological manifestations. All participants suffered from moderate to severe pain. There was a positive association between corticospinal excitability and the effectiveness of the CPM (rs = 0.67, p = 0.01, n = 13). There was also a positive relationship between pain intensity and corticospinal excitability (rs = 0.45, p = 0.03, n = 23), and between pain intensity and temporal summation (rs = 0.58, p = 0.01, n = 18). The results of this study highlight some of the central nervous system changes that could be involved in knee OA and underline the importance of interindividual variability to better understand and explain the semiology and pathophysiology of knee OA. [ABSTRACT FROM AUTHOR]

Purpose: We have previously demonstrated the upper limit of complete spatial summation (Ricco's area) to increase in non‐pathological axial myopia compared to non‐myopic controls. This study sought to investigate whether temporal summation is also altered in axial myopia to determine if this aspect of visual function, like in glaucoma, is influenced by reductions in retinal ganglion cell (RGC) density. Methods: Achromatic contrast thresholds were measured for a GIII‐equivalent stimulus (0.43° diameter) of six different stimulus durations (1–24 frames, 1.1–187.8 ms) in 24 participants with axial myopia (mean spherical refractive error: −4.65D, range: −1.00D to −11.25D, mean age: 34.1, range: 21–57 years) and 21 age‐similar non‐myopic controls (mean spherical refractive error: +0.87D, range: −0.25D to +2.00D, mean age: 31.0, range: 18–55 years). Measurements were performed at 10° eccentricity along the 90°, 180°, 270° and 360° meridians on an achromatic 10 cd/m2 background. The upper limit of complete temporal summation (critical duration, CD) was estimated from the data with iterative two‐phase regression analysis. Results: There was no significant difference (p = 0.90, Mann–Whitney U‐test) in median CD between myopes (median: 44.3 ms; IQR: 26.5, 51.2) and non‐myopes (median: 41.6 ms; IQR: 27.3, 48.5). Despite RGC numbers underlying the stimulus being significantly lower in the myopic group (p < 0.001), no relationship was observed between the CD estimate and co‐localised RGC number (Pearson's r = −0.13, p = 0.43) or ocular length (Pearson's r = −0.08, p = 0.61). Conclusions: Unlike spatial summation, temporal summation is unchanged in myopia. This contrasts with glaucoma where both temporal and spatial summation are altered. As such, perimetric methods optimised to test for anomalies of temporal summation may provide a means to differentiate between conditions causing only a reduced RGC density (e.g., myopia), and pathological processes causing both a reduced RGC density and RGC dysfunction (e.g., glaucoma). [ABSTRACT FROM AUTHOR]

'Non-inflammatory' pain, pain that is not associated with measures of inflammation, is common in patients with inflammatory arthritis including RA. One important cause of non-inflammatory pain is concomitant fibromyalgia. Systematic review has shown that fibromyalgia is common in inflammatory arthritis including RA affecting 1 in 5 patients and is associated with higher disease activity scores due to inflated tender joint count and patient global assessment. Consequently, many patients with RA and concomitant fibromyalgia may fail to reach treatment target and switch to alternate disease modifying drugs frequently. European Alliance of Association for Rheumatology has highlighted that concomitant fibromyalgia is an important consideration in assessing difficult-to-treat RA. The incidence and prevalence of fibromyalgia are higher in RA than the general population, raising the possibility that fibromyalgia may be 'secondary' to RA rather than a concomitant disease. The precise mechanisms whereby patients with RA develop fibromyalgia are unknown. In this review, we discussed fibromyalgia in RA, its clinical impact and epidemiology as well as data suggesting fibromyalgia might be 'secondary'. Lastly, we reviewed potential pathogenic mechanisms which included inflammatory cytokines sensitizing nociceptive neurones, temporal summation, also known as windup, from chronic pain and impaired coping from poor quality sleep and mental well-being. Deciphering the exact mechanisms may lead to treatment strategies that prevent development of secondary fibromyalgia and will address a common factor associated with difficult-to-treat RA. [ABSTRACT FROM AUTHOR]

Abstract Background Deficient endogenous pain modulation has been implicated in the development and exacerbation of chronic orofacial pain. To date, relatively little is known regarding the function of the endogenous pain modulation in patients with burning mouth syndrome (BMS). This case–control study investigated endogenous pain modulation in women with BMS. Methods Conditioned pain modulation (CPM) was assessed upon temporal summation (TSP) of thermal pain. Forty female subjects, 20 BMS patients and 20 age-matched control subjects, were included in a 2 session-protocol. Mechanical and thermal pain thresholds were measured on the forearm and hand. TSP was obtained using repetitive laser-evoked thermal stimuli applied on the non-dominant hand, at an intensity yielding to moderate pain. During TSP, CPM was produced by immersing the contralateral foot in a water bath at painful cold (8 °C) temperature. In control conditions, the foot was immersed in a water bath at not painful (30 °C) temperature. Results BMS was not associated with any impairment in thermal as well as mechanical extracephalic pain thresholds. TSP and CPM efficacy were similar in BMS patients and control subjects. However, BMS patients exhibited enhanced extracephalic heat hyperalgesia. Conclusion This study reveals that there is no impairment of endogenous pain inhibition mechanisms in BMS patients, but rather an increase in pain facilitation.

Objective: To assess the effects of 5 different durations of electro-dry needling (EDN) on asymptomatic individuals’ pain response after repeated noxious thermal stimuli. Design: Randomized, non-controlled intervention trial. Setting: University laboratory. Participants: Asymptomatic participants (N=50) were recruited for the study and randomized into 5 groups. There were 33 women with an average age of 26.8 (±4.8) years. To participate in the study, individuals had to be between the ages of 18 and 40, free of any musculoskeletal injury which prevented participation of daily activities, and not pregnant or trying to become pregnant. Interventions: Participants were randomly assigned to receive 5 different durations of EDN: 10, 15, 20, 25, and 30 minutes. To perform the EDN, 2 monofilament needles were inserted lateral to the lumbar spinous processes of L3 and L5 on the right. Needles were left in situ with electrical stimulation at a frequency of 2 Hz and an amplitude which resulted in a 3 to 6 out of 10 intensity pain rating by the participant. Main Outcome Measures: The change in the magnitude of pain in response to repetitive heat-pulses before and after the EDN procedure. Results: There was a significant reduction in the magnitude of pain in response across the groups after EDN (F(1,42)=94.12, P

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 Background Postoperative axial pain (PAP), characterized by pain and/or stiffness around the posterior neck, periscapular areas and/or shoulder region, is a vexing complication affecting 5–60% of patients undergoing posterior cervical decompression. Given its relatively high frequency and negative impact on patients’ physical and mental status, efforts preoperatively to confirm patients at risk of developing PAP to offer more efficient pain management to minimize this complication have a high priority. The aim of this study is to investigate the role of preoperative dynamic quantitative sensory testing (QST) in predicting the PAP after posterior cervical decompression. Methods This longitudinal observational study included 122 patients with degenerative cervical myelopathy undergoing laminoplasty or laminectomy. Preoperatively, all patients underwent the assessment of pressure pain thresholds (PPTs) at local and remote pain-free areas and both temporal summation (TS) and conditioned pain modulation (CPM) at remote pain free-areas. These patients underwent further pain-related, psychosocial and clinical function assessments before and/or after operation. Results In the present study, 21 patients (21/122, 17.2%) developed PAP, and the 6-month postoperative follow-up demonstrated that 8 of these 21 patients developed chronic PAP (CPAP). All preoperative covariates with significant differences between the PAP and non-PAP groups were subjected to multivariate logistic regression, and the presence of preoperative axial pain, surgical plan including C2 decompression, total international physical activity questionnaire score (cutoff value [CV]: 2205.5, sensitivity: 82.4%; specificity: 61.1%) and TS value (CV: 2.5, sensitivity: 42.9%; specificity: 83.2%) were independently associated with PAP (P

Background: Population voltage imaging is used for studying brain physiology and brain circuits. Using a genetically encoded voltage indicator (GEVI), “VSFP” or “ASAP2s”, or a voltage-sensitive dye, Di-4-Anepps, we conducted population voltage imaging in brain slices. The resulting optical signals, optical local field potentials (LFPs), were used to evaluate the performances of the 3 voltage indicators. Methods: In brain slices prepared from VSFP-transgenic or ASAP2s-transgenic mice, we performed multi-site optical imaging of evoked cortical depolarizations - compound excitatory postsynaptic potentials (cEPSPs). Optical signal amplitudes (ΔF/F) and cEPSP decay rates (OFF rates) were compared using analysis of variance (ANOVA) followed by unpaired Student’s t test (31–104 data points per voltage indicator). Results: The ASAP2s signal amplitude (ΔF/F) was on average 3 times greater than Di-4-Anepps, and 7 times greater than VSFP. The optical cEPSP decay (OFF rate) was the slowest in Di-4-Anepps and fastest in ASAP2s. When ASAP2s expression was weak, we observed slow, label-free (autofluorescence, metabolic) optical signals mixed into the ASAP2s traces. Fast hyperpolarizations, that typically follow depolarizing cortical transients (afterhyperpolarizations), were prominent in ASAP2s but not present in the VSFP and Di-4-Anepps experiments. Conclusions: Experimental applications for ASAP2s may potentially include systems neuroscience studies that require voltage indicators with large signal amplitude (ΔF/F), fast decay times (fast response time is needed for monitoring high frequency brain oscillations), and/or detection of brain patches in transiently hyperpolarized states (afterhyperpolarization).

Background: Deficient endogenous pain modulation has been implicated in the development and exacerbation of chronic orofacial pain. To date, relatively little is known regarding the function of the endogenous pain modulation in patients with burning mouth syndrome (BMS). This case–control study investigated endogenous pain modulation in women with BMS. Methods: Conditioned pain modulation (CPM) was assessed upon temporal summation (TSP) of thermal pain. Forty female subjects, 20 BMS patients and 20 age-matched control subjects, were included in a 2 session-protocol. Mechanical and thermal pain thresholds were measured on the forearm and hand. TSP was obtained using repetitive laser-evoked thermal stimuli applied on the non-dominant hand, at an intensity yielding to moderate pain. During TSP, CPM was produced by immersing the contralateral foot in a water bath at painful cold (8 °C) temperature. In control conditions, the foot was immersed in a water bath at not painful (30 °C) temperature. Results: BMS was not associated with any impairment in thermal as well as mechanical extracephalic pain thresholds. TSP and CPM efficacy were similar in BMS patients and control subjects. However, BMS patients exhibited enhanced extracephalic heat hyperalgesia. Conclusion: This study reveals that there is no impairment of endogenous pain inhibition mechanisms in BMS patients, but rather an increase in pain facilitation. [ABSTRACT FROM AUTHOR]

Although current evidence supports the use of dry needling for improving some clinical outcomes in people with neck pain, no previous research explored the effects of dry needling on the central processing of pain and autonomic nervous system in this population. Therefore, this clinical trial aimed to compare the effects of real and sham dry needling on autonomic nervous system function, pain processing as well as clinical and psychological variables in patients with chronic nonspecific neck pain. A double-blinded randomized clinical trial including 60 patients with neck pain was conducted. Patients were randomized to the real needling (n = 30) or sham needling (n = 30) group. Skin conductance (SC), pressure pain thresholds (PPTs), temporal summation (TS), conditioned pain modulation (CPM) as well as pain intensity, related-disability, catastrophism, and kinesiophobia levels were assessed by an assessor blinded to the allocation intervention. The results did not find significant group * time interactions for most outcomes, except for the global percentage of change of SC values (mean: F = 35.90, p < 0.001, η p 2 = 0.459; minimum: F = 33.99, p = 0.839, η p 2 = 0.371; maximum: F = 24.71, p < 0.001, η p 2 = 0.037) and PPTs at C5-C6 joint in the same side of needling (F = 9.982; p = 0.003; = 0.147), in favor of the dry needling group. Although the proportion of subjects experiencing moderate to large self-perceived improvement after the intervention was significantly higher (X2 = 8.297; p = 0.004) within the dry needling group (n = 18, 60%) than in the sham needling group (n = 7, 23.3%), both groups experienced similar improvements in clinical and psychological variables. Our results suggested that dry needling applied to patients with chronic nonspecific neck pain produced an immediate decrease in mechanical hyperalgesia at local sites and produced an increase in skin conductance as compared with sham needling. No changes in central pain processing were observed. A single session of sham or real dry needling was similarly effective for decreasing related disability, pain intensity, catastrophism, and kinesiophobia levels. Further studies are needed to better understand the clinical implications of autonomic nervous system activation on central sensitization and pain processing in the long-term after the application of dry needling. [ABSTRACT FROM AUTHOR]

Background: Native Americans (NAs) are more likely to experience chronic pain than non-Hispanic Whites (NHWs); however, the proximate causes predisposing NAs to chronic pain remain elusive. Likely due to centuries of adversity, discrimination, and marginalization, NAs report greater psychological stress than NHWs, which may place them at risk for sleep problems, a well-established risk factor for chronic pain onset.Purpose: This study examined the effects of psychological stress and sleep problems on subjective and physiological measures of pain processing in NAs and NHWs.Methods: Structural equation modeling was used to determine whether ethnicity (NA or NHW) was associated with psychological stress or sleep problems and whether these variables were related to conditioned pain modulation of pain perception (CPM-pain) and the nociceptive flexion reflex (CPM-NFR), temporal summation of pain (TS-pain) and NFR (TS-NFR), and pain tolerance in a sample of 302 (153 NAs) pain-free participants.Results: NAs experienced more psychological stress (Estimate = 0.027, p = .009) and sleep problems (Estimate = 1.375, p = .015) than NHWs. When controlling for age, sex, physical activity, BMI, and general health, NA ethnicity was no longer related to greater sleep problems. Psychological stress was also related to sleep problems (Estimate = 30.173, p = <.001) and psychological stress promoted sleep problems in NAs (indirect effect = 0.802, p = .014). In turn, sleep problems were associated with greater TS-pain (Estimate = 0.714, p = .004), but not other pain measures.Conclusions: Sleep problems may contribute to chronic pain risk by facilitating pain perception without affecting facilitation of spinal neurons or endogenous inhibition of nociceptive processes. Since psychological stress promoted pain facilitation via enhanced sleep problems, efforts to reduce psychological stress and sleep problems among NAs may improve health outcomes. [ABSTRACT FROM AUTHOR]

To investigate the presence of altered central pain processing in patients with failed back surgery syndrome (FBSS) using quantitative sensory testing (QST). This study included 34 patients with FBSS, 102 patients post-lumbar surgery without low back pain (LBP), and 102 healthy subjects. All subjects underwent both pressure pain threshold (PPT) and conditioned pain modulation (CPM) in both local and remote pain-free areas, as well as temporal summation (TS) in a remote pain-free area. All patient subjects were assessed using the Pain Catastrophizing Scale (PCS), Beck Anxiety Inventory (BAI), Beck Depression Index (BDI), Numeric rating pain scale (NRS) and Oswestry Disability Index (ODI). Compared with both control groups, FBSS patients showed a reduction in both PPT and CPM in both tested areas, along with increased TS in a pain-free area (P < 0.05). Furthermore, the patients with FBSS had a significantly higher prevalence of anxiety, depression and pain catastrophizing thoughts than the patient controls (P < 0.05). In the FBSS patients, there was a significant correlation between LBP at rest and both CPM and TS in the pain-free areas, and QST measurements were also associated with the ODI, PCS and BAI (P < 0.05). These findings support the existence of augmented central pain processing in patients with FBSS, which may be caused by dysfunction of endogenous pain facilitation and inhibition. This central amplification of pain may contribute to both LBP intensity and disability in FBSS patients. Therefore, treatment efforts should take into account functional alterations in the central nervous system of FBSS patients. [ABSTRACT FROM AUTHOR]

Background: Conflicting results exist between somatosensory profiles of patients with temporomandibular myalgia (TMDm). The objective of this review was to examine whether adults with TMDm show altered responses to dynamic quantitative sensory tests compared with healthy controls. Methods: We searched five electronic databases for studies, excluding those without suitable controls or where TMDm was associated with confounding non‐musculoskeletal disorders. Risk of bias was assessed with the SIGN case‐control study checklist. Findings were structured around dynamic quantitative sensory tests and their localization. Where possible, we performed meta‐analysis with a random inverse variance model to compare patients with TMDm and healthy controls. Statistical heterogeneity was estimated with Chi² test and inconsistency index, I². Results: We extracted data from 23 studies comprising 1284 adults with chronic TMDm and 2791 healthy controls. Risk of bias was assessed as high for 20 studies. Mechanical temporal summation, the most studied phenomenon (14 studies), is increased in the upper limb of patients with TMDm (SMD = 0.43; 95% CI:.11 to.75; p =.009) but not in the jaw area (p =.09) or in the cervical area (p =.29). Very little evidence for altered thermal temporal summation (five studies), conditioned pain modulation (seven studies), exercise‐induced hypoalgesia (two studies), placebo analgesia (two studies), stress‐induced hypoalgesia (one study) and offset analgesia (one study) was found. Discussion: A major limitation of this review was the risk of bias of included studies. Future studies would benefit from following methodological guidelines and consideration of confounding factors. [ABSTRACT FROM AUTHOR]

IntroductionFibromyalgia (FM) is associated with dysfunctional pain modulation mechanisms, including central sensitization. Experimental pain measurements, such as temporal summation (TS), could serve as markers of central sensitization and have been previously studied in these patients, with conflicting results. Our objective in this study was to explore the relationships between two different protocols of TS (phasic and tonic) and test the associations between these measures and other clinical variables.Materials and MethodsIn this cross-sectional analysis of a randomized clinical trial, patients were instructed to determine their pain-60 test temperature, then received one train of 15 repetitive heat stimuli and rated their pain after the 1st and 15th stimuli: TSPS-phasic was calculated as the difference between those. We also administered a tonic heat test stimulus at the same temperature continuously for 30 s and asked them to rate their pain levels after 10 s and 30 s, calculating TSPS-tonic as the difference between them. We also collected baseline demographic data and behavioral questionnaires assessing pain, depression, fatigue, anxiety, sleepiness, and quality of life. We performed univariable analyses of the relationship between TSPS-phasic and TSPS-tonic, and between each of those measures and the demographic and clinical variables collected at baseline. We then built multivariable linear regression models to find predictors for TSPS-phasic and TSPS-tonic, while including potential confounders and avoiding collinearity.ResultsFifty-two FM patients were analyzed. 28.85% developed summation during the TSPS-phasic protocol while 21.15% developed summation during the TSPS-tonic protocol. There were no variables associated TSPS phasic or tonic in the univariable analyses and both measures were not correlated. On the multivariate model for the TSPS-phasic protocol, we found a weak association with pain variables. BPI-pain subscale was associated with more temporal summation in the phasic protocol (ß = 0.38, p = 0.029), while VAS for pain was associated with less summation in the TSPS-tonic protocol (ß = −0.5, p = 0.009).ConclusionOur results suggest that, using heat stimuli with pain-60 temperatures, a TSPS-phasic protocol and a TSPS-tonic protocol are not correlated and could index different neural responses in FM subjects. Further studies with larger sample sizes would be needed to elucidate whether such responses could help differentiating subjects with FM into specific phenotypes.

Abstract Background Biopsychosocial factors above and beyond pathoanatomical changes likely contribute to the severity of chronic low back pain. A pro-nociceptive endogenous pain modulatory balance (↓inhibition and ↑facilitation) may be an important contributor to chronic low back pain severity and physical function; however, additional research is needed to address this possibility. The objective of this study was to determine whether quantitative sensory tests of endogenous pain inhibition and facilitation prospectively predict movement-evoked pain and cLBP severity self-reported on a validated questionnaire. Methods One hundred thirty-four individuals with chronic low back pain were enrolled in this two-session study. During the first study session, temporal summation of mechanical pain and conditioned pain modulation were assessed at the lumbar spine to determine endogenous pain facilitation and inhibition, respectively. One week later, participants returned for a second study session whereby they reported their pain severity and pain interference using the Brief Pain Inventory-Short Form. Movement-evoked pain and physical function capacity were assessed upon completion of the balance, walking, and transition from sit to stand tests of the Short Physical Performance Battery. Results Temporal summation of mechanical pain, but not conditioned pain modulation, significantly and prospectively predicted greater movement-evoked pain and poorer physical function on the Short Physical Performance Battery. Neither temporal summation nor conditioned pain modulation were significantly related to self-reported pain severity or pain interference on the Brief Pain Inventory-Short Form. Conclusions Findings suggest that a pro-nociceptive pain modulatory balance characterized by enhanced pain facilitation may be an important driver of movement-evoked pain severity and poor physical function in individuals with chronic low back pain.

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]

Background: Postoperative axial pain (PAP), characterized by pain and/or stiffness around the posterior neck, periscapular areas and/or shoulder region, is a vexing complication affecting 5-60% of patients undergoing posterior cervical decompression. Given its relatively high frequency and negative impact on patients' physical and mental status, efforts preoperatively to confirm patients at risk of developing PAP to offer more efficient pain management to minimize this complication have a high priority. The aim of this study is to investigate the role of preoperative dynamic quantitative sensory testing (QST) in predicting the PAP after posterior cervical decompression.Methods: This longitudinal observational study included 122 patients with degenerative cervical myelopathy undergoing laminoplasty or laminectomy. Preoperatively, all patients underwent the assessment of pressure pain thresholds (PPTs) at local and remote pain-free areas and both temporal summation (TS) and conditioned pain modulation (CPM) at remote pain free-areas. These patients underwent further pain-related, psychosocial and clinical function assessments before and/or after operation.Results: In the present study, 21 patients (21/122, 17.2%) developed PAP, and the 6-month postoperative follow-up demonstrated that 8 of these 21 patients developed chronic PAP (CPAP). All preoperative covariates with significant differences between the PAP and non-PAP groups were subjected to multivariate logistic regression, and the presence of preoperative axial pain, surgical plan including C2 decompression, total international physical activity questionnaire score (cutoff value [CV]: 2205.5, sensitivity: 82.4%; specificity: 61.1%) and TS value (CV: 2.5, sensitivity: 42.9%; specificity: 83.2%) were independently associated with PAP (P < 0.05). Logistic regression further revealed that the presence of preoperative axial pain, TS value (CV: 2.5, sensitivity: 62.5%; specificity: 83.2%) and CPM value (CV: 0.65, sensitivity: 87.5%; specificity: 61.4%) were significant predictors of CPAP (P < 0.05).Conclusions: The findings of this study support the hypothesis that preoperative endogenous pain modulation efficiency may be associated with axial pain after posterior cervical decompression. Clinically, preoperative estimation of both TS and CPM in remote pain-free areas may provide additional useful information for identifying patients who may be at risk of developing both PAP and CPAP, which may be beneficial in enabling stratification in the perioperative period of patients based on individual vulnerabilities to avoid/reduce this complication. [ABSTRACT FROM AUTHOR]

Background: Knee osteoarthritis (OA) is among the most common and disabling persistent pain conditions, with increasing prevalence and impact around the globe. In the U.S., the rising prevalence of knee OA has been paralleled by an increase in annual rates of total knee arthroplasty (TKA), a surgical treatment option for late-stage knee OA. While TKA outcomes are generally good, post-operative trajectories of pain and functional status vary substantially; a significant minority of patients report ongoing pain and impaired function following TKA. A number of studies have identified sets of biopsychosocial risk factors for poor post-TKA outcomes (e.g., comorbidities, negative affect, sensory sensitivity), but few prospective studies have systematically evaluated the unique and combined influence of a broad array of factors.Methods: This multi-site longitudinal cohort study investigated predictors of 6-month pain and functional outcomes following TKA. A wide spectrum of relevant biopsychosocial predictors was assessed preoperatively by medical history, patient-reported questionnaire, functional testing, and quantitative sensory testing in 248 patients undergoing TKA, and subsequently examined for their predictive capacity.Results: The majority of patients had mild or no pain at 6 months, and minimal pain-related impairment, but approximately 30% reported pain intensity ratings of 3/10 or higher. Reporting greater pain severity and dysfunction at 6 months post-TKA was predicted by higher preoperative levels of negative affect, prior pain history, opioid use, and disrupted sleep. Interestingly, lower levels of resilience-related "positive" psychosocial characteristics (i.e., lower agreeableness, lower social support) were among the strongest, most consistent predictors of poor outcomes in multivariable linear regression models. Maladaptive profiles of pain modulation (e.g., elevated temporal summation of pain), while not robust unique predictors, interacted with psychosocial risk factors such that the TKA patients with the most pain and dysfunction exhibited lower resilience and enhanced temporal summation of pain.Conclusions: This study underscores the importance of considering psychosocial (particularly positively-oriented resilience variables) and sensory profiles, as well as their interaction, in understanding post-surgical pain trajectories. [ABSTRACT FROM AUTHOR]

Background: Temporal summation and conditioned pain modulation (CPM) can be measured using a thermode and cold pressor test (CPTest). Unfortunately, these complex and expensive tools are ill-suited for routine clinical assessments. Aims: We aimed to compare the temporal summation and CPM obtained with the thermode + CPTest paradigm to those obtained with a novel paradigm using transcutaneous electrical nerve stimulation (TENS). Methods: We assessed temporal summation and CPM in 29 healthy participants, using two paradigms (random order): TENS, and thermode + CPTest. In the TENS paradigm, both the conditioning stimulus (CS) and the test stimulus (TS) were delivered using TENS; in the thermode + CPTest paradigm, the CS consisted of a CPTest and the TS was delivered using a thermode. We compared the average temporal summation and CPM evoked by the two paradigms. Results: Average temporal summation was similar for both modalities (P = 0.90), and the number of participants showing temporal summation was similar in both paradigms (19 with thermode vs. 18 with TENS; P = 1.00). Average CPM response was larger following the thermode + CPTest than following the TENS (P = 0.005), and more participants showed CPM with the thermode + CPTest paradigm compared to the TENS paradigm (24 vs. 14; P = 0.01). Conclusions: Both paradigms were roughly equivalent in the ability to evoke temporal summation (although response to one modality did not predict response to the other), but the TENS paradigm appeared to be less apt to induce a CPM response than the thermode + CPTest paradigm.

Wind-up like pain or temporal summation of pain is a phenomenon in which pain sensation is increased in a frequency-dependent manner by applying repeated noxious stimuli of uniform intensity. Temporal summation in humans has been studied by observing the increase in pain or flexion reflex by repetitive electrical or thermal stimulations. Nonetheless, because the measurement is accompanied by severe pain, a minimally invasive method is desirable. Gradual augmentation of flexion reflex and pain induced by repetitive stimulation of the sural nerve was observed using three stimulation methods—namely, bipolar electrical, magnetic, and monopolar electrical stimulation, with 11 healthy male subjects in each group. The effects of frequency, intensity, and number of repetitive stimuli on the increase in the magnitude of flexion reflex and pain rating were compared among the three methods. The reflex was measured using electromyography (EMG) from the short head of the biceps femoris. All three methods produced a frequency- and intensity-dependent progressive increase in reflex and pain; pain scores were significantly lower for magnetic and monopolar stimulations than for bipolar stimulation (P < 0.05). The slope of increase in the reflex was steep during the first 4–6 stimuli but became gentler thereafter. In the initial phase, an increase in the reflex during the time before signals of C-fibers arrived at the spinal cord was observed in experiments using high-frequency stimulation, suggesting that wind-up was caused by inputs of A-fibers without the involvement of C-fibers. Magnetic and monopolar stimulations are minimally invasive and useful methods for observing the wind-up of the flexion reflex in humans. Monopolar stimulation is convenient because it does not require special equipment. There is at least a partial mechanism underlying the wind-up of the flexion reflex that does not require C-fibers. [ABSTRACT FROM AUTHOR]

Objective: Assessing mechanical pain thresholds from trigeminal, cervical, and distal pain‐free areas during the four phases of a migraine cycle in patients with episodic migraine (EM). Methods: This multicenter, cross‐sectional, observational study conducted in Parma and Genoa's Headache Centers assessed quantitative sensory tests during the four migraine phases in patients with EM compared to controls. Temporal summation of pain (TSP), static pressure pain threshold (sPPT), and mechanical pinprick pain threshold (MPT) were assessed from the trigeminal area, sPPT and dynamic PPT (dPPT) from the cervical area, sPPT and MPT over the hand, and sPPT from the tibialis anterior. Results: A total of 135 patients and 46 controls were included. TSP was facilitated in ictal EM (EM vs. controls: mean [standard deviation] 2.7 [2.0] vs. 1.4 [1.8]; p = 0.004); trigeminal sPPT and MPT were reduced in interictal (sPPT: 198.5 [79.3] kPa; p = 0.021; MPT: 12.6 [15.7] g; p = 0.001), preictal (sPPT: 200.6 [71.6] kPa; p = 0.033; MPT: 10.7 [12.4] g; p < 0.001), ictal (sPPT: 171.4 [95.9] kPa; p < 0.001; MPT: 7.3 [12.0] g; p < 0.001), and postictal EM (sPPT: 182.2 [76.3] kPa; p = 0.006; MPT: 10.1 [14.9] g; p = 0.001), compared to controls (sPPT: 238.3 [73.8] kPa; MPT: 21.9 [17.3] g). Cervical sPPTs and dPPT were reduced in interictal (sPPT upper cervical spine: 420.5 [176.7] kPa; p = 0.031; sPPT lower cervical spine: 458.6 [207.3] kPa; p = 0.002; dPPT: 4826.5 [2698.0] g; p < 0.001), preictal (sPPT upper cervical spine: 389.3 [133.4] kPa; p = 0.006; sPPT lower cervical spine: 450.8 [174.3] kPa; p = 0.005; dPPT: 4184.2 [2628.3] g; p < 0.001), ictal (sPPT upper cervical spine: 379.9 [205.6] kPa p = 0.003; sPPT lower cervical spine: 436.3 [271.1] kPa; p = 0.001; dPPT: 3838.3 [2638.7] g; p < 0.001), and postictal EM (sPPT upper cervical spine: 385.5 [131.6] kPa; p = 0.020; sPPT lower cervical spine: 413.0 [150.3] kPa; p = 0.002; dPPT: 4679.6 [2894.9] g; p = 0.001), compared to controls (sPPT upper cervical spine: 494.9 [171.5] kPa; sPPT lower cervical spine: 586.9 [210.8] kPa; dPPT: 7693.9 [2896.8] g). Preictal EM had reduced hand sPPT and MPT (sPPT: 248.8 [96.6] kPa vs. 319.8 [112.3] kPa; p = 0.006; MPT: 23.6 [12.2] g vs. 32.5 [14.4] g; p = 0.035), while EM in the other phases showed reduction in hand MPT (interictal: 22.3 [15.6] g vs. 32.5 [14.4] g; p = 0.002; ictal: 22.4 [17.0] g vs. 32.5 [14.4] g; p = 0.004; postictal: 24.2 [18.8] g vs. 32.5 [14.4] g; p = 0.003) without significant reduction in hand sPPT. No difference in sPPT over the tibialis anterior was found. Hand MPT was negatively correlated with longer disease duration (r = −0.25; p = 0.011) and hand sPPT was negatively correlated with higher drug usage (r = −0.31; p = 0.002). TSP during the ictal phase was positively correlated with the physical (r = 0.38; p = 0.040) and emotional headache‐related disability (r = 0.53; p = 0.003). Conclusion: In all phases of the migraine cycle, patients with EM show signs of sensitization in the trigeminocervical area, with patients with the most prominent sensitization in the ictal phase. Signs of widespread sensitization were consistent in the preictal phase in patients with EM and in the subgroups of patients with EM with the longest disease duration and more usage of symptomatic drugs. [ABSTRACT FROM AUTHOR]

Wind-up like pain or temporal summation of pain is a phenomenon in which pain sensation is increased in a frequency-dependent manner by applying repeated noxious stimuli of uniform intensity. Temporal summation in humans has been studied by observing the increase in pain or flexion reflex by repetitive electrical or thermal stimulations. Nonetheless, because the measurement is accompanied by severe pain, a minimally invasive method is desirable. Gradual augmentation of flexion reflex and pain induced by repetitive stimulation of the sural nerve was observed using three stimulation methods—namely, bipolar electrical, magnetic, and monopolar electrical stimulation, with 11 healthy male subjects in each group. The effects of frequency, intensity, and number of repetitive stimuli on the increase in the magnitude of flexion reflex and pain rating were compared among the three methods. The reflex was measured using electromyography (EMG) from the short head of the biceps femoris. All three methods produced a frequency- and intensity-dependent progressive increase in reflex and pain; pain scores were significantly lower for magnetic and monopolar stimulations than for bipolar stimulation (P < 0.05). The slope of increase in the reflex was steep during the first 4–6 stimuli but became gentler thereafter. In the initial phase, an increase in the reflex during the time before signals of C-fibers arrived at the spinal cord was observed in experiments using high-frequency stimulation, suggesting that wind-up was caused by inputs of A-fibers without the involvement of C-fibers. Magnetic and monopolar stimulations are minimally invasive and useful methods for observing the wind-up of the flexion reflex in humans. Monopolar stimulation is convenient because it does not require special equipment. There is at least a partial mechanism underlying the wind-up of the flexion reflex that does not require C-fibers.

Jiang-Ti Kong,1 Epifanio Bagarinao,2 Richard A Olshen,3 Sean Mackey1 1Department Of Anesthesiology, Perioperative And Pain Medicine, Stanford University School of Medicine, Stanford, CA, USA; 2Brain And Mind Research Center, Nagoya University, Nagoya, Japan; 3Department of Biomedical Data Science, School of Medicine, Stanford University, Stanford, CA, USACorrespondence: Jiang-Ti KongDepartment of Anesthesiology, Perioperative and Pain Medicine, Stanford University School Of Medicine, 1070 Arastradero Road, Suite 200, Palo Alto, CA 94304, USATel +1 650-723-1235Fax +1 650-725-9642Email jtkong@stanford.eduBackground: Temporal summation (TS) refers to the increased perception of pain with repetitive noxious stimuli. While thermal TS is generally considered a behavioral correlate of spinal windup, noxious heat pulses also trigger additional sensory processes which were modeled in this study.Methods: Nineteen healthy volunteers (9 females, mean age 29.2, SD 10.5) underwent two identical TS experiments, spaced a week apart. The TS paradigm consisted of 10 identical heat pulses with individualized temperatures at the thenar eminence (0.5Hz). We extracted 3 features from continuous TS response curves: Lag, time to first feel pain; Slope, the rate of pain increase between the first and most painful heat pulse; and Delta, the maximum drop in pain after peak pain is reached. We then examined the within-individual stability of these features, followed by the Pearson’s correlations among these features and between the features and negative affect.Results: All 3 features were stable over 1 week. Lag and Delta were negatively correlated (r = −0.5, p = 0.042). Slope did not correlate with Lag or Delta, but strongly correlated with a traditional TS measure, first pulse pain and peak pain difference (r = 0.91, p < 0.0001). Negative affects such as trait and state anxiety were negatively correlated with baseline (r = −0.49, p = 0.031) and peak stimulating temperature (r = −0.48, p = 0.039), respectively, suggesting an association between anxiety and greater pain sensitivity.Conclusion: We were able to decouple spinal windup from other perceptual processes generated by phasic thermal TS paradigms and demonstrate temporal stability of these curve features. These curve features may help better characterize the complex sensory response to noxious heat pulses and serve as biomarkers to profile patients with chronic pain.Keywords: thermal, temporal summation, windup, anxiety, depression, test–retest stability

The human visual system is continuously exposed to a natural environment with static and moving objects that the visual system needs to continuously integrate and process. Glass patterns (GPs) are a class of visual stimuli widely used to study how the human visual system processes and integrates form and motion signals. GPs are made of pairs of dots that elicit a strong percept of global form. A rapid succession of unique frames originates dynamic GPs. Previous psychophysical studies showed that dynamic translational GPs are easier to detect than the static version because of the spatial summation across the unique frames composing the pattern. However, it is not clear whether the same mechanism is involved in dynamic circular GPs. In the present study, we psychophysically investigated the role of the temporal and spatial summation in the perception of both translational and circular GPs. We manipulated the number of unique frames in dynamic GPs and the update rate of the frames presentation. The results suggest that spatial and temporal summation across unique frames takes place for both translational and circular GPs. Moreover, the number of unique frames and the pattern update rate equally influence the discrimination thresholds of translational and circular GPs. These results show that form and motion integration is likely to be processed similarly for translational and circular GPs. [ABSTRACT FROM AUTHOR]

Objective Endogenous pain modulation can be quantified through the use of various paradigms. Commonly used paradigms include conditioned pain modulation (CPM), offset analgesia (OA), spatial summation of pain (SSP), and temporal summation of pain (TSP), which reflect spatial and temporal aspects of pro- and antinociceptive processing. Although these paradigms are regularly used and are of high clinical relevance, the underlying physiological mechanisms are not fully understood. Design The aim of this study is therefore to assess the association between these paradigms by using comparable protocols and methodological approaches. Setting University campus. Subjects Healthy and pain-free volunteers (n = 48) underwent psychophysical assessment of CPM, OA, SSP, and TSP (random order) at the same body area (volar nondominant forearm) with individualized noxious stimuli. Methods CPM included heat stimuli before, during, and after a noxious cold-water bath, whereas for OA, three heat stimuli were applied: baseline trial, offset trial, and constant trial. For the SSP paradigm, two differently sized heat stimulation areas were evaluated, whereas for TSP, the first and last stimulus of 10 consecutive short heat stimuli were assessed. A computerized visual analog scale was used to continuously evaluate pain intensity. The magnitudes of all associations between all paradigm pairs were analyzed with Spearman's correlation, and individual influencing factors were assessed with a multivariate linear regression model. Results Weak to moderate correlations among all four paradigms were found (P  > 0.05), and no distinct influencing factors were identified. Conclusions A limited association between pain modulation paradigms suggests that CPM, OA, SSP, and TSP assess distinct aspects of endogenous analgesia with different underlying physiological mechanisms. [ABSTRACT FROM AUTHOR]

Spatial information of nociceptive stimuli applied in the skin of healthy humans is integrated in the spinal cord to determine the appropriate withdrawal reflex response. Double-simultaneous stimulus applied in different skin sites are integrated, eliciting a larger reflex response. The temporal characteristics of the stimuli also modulate the reflex, e.g., by temporal summation. The primary aim of this study was to investigate how the combined tempo-spatial aspects of two stimuli are integrated in the nociceptive system. This was investigated by delivering single- and double-simultaneous stimulation and sequential stimulation with different interstimulus intervals (ISIs ranging 30-500 ms) to the sole of the foot of 15 healthy subjects. The primary outcome measure was the size of the nociceptive withdrawal reflex (NWR) recorded from the tibialis anterior (TA) and biceps femoris (BF) muscles. Pain intensity was measured using a numerical rating scale (NRS) scale. Results showed spatial summation in both TA and BF when delivering simultaneous stimulation. Simultaneous stimulation provoked larger reflexes than sequential stimulation in TA, but not in BF. Larger ISIs elicited significantly larger reflexes in TA, whereas the opposite pattern occurred in BF. This differential modulation between proximal and distal muscles suggests the presence of spinal circuits eliciting a functional reflex response based on the specific tempo-spatial characteristics of a noxious stimulus. No modulation was observed in pain intensity ratings across ISIs. Absence of modulation in the pain intensity ratings argues for an integrative mechanism located within the spinal cord governed by a need for efficient withdrawal from a potentially harmful stimulus. [ABSTRACT FROM AUTHOR]

An important consideration in the design of any electrical stimulation paradigm is the stimulus current waveform. In this paper we have investigated, through numerical modeling, a stimulus current waveform designed ad hoc to control the neural fibers temporal activation according to their different diameter. The stimulus consists of a series of depolarized pre-pulses, both over- and subthreshold, and designed based on the nonlinear conductance properties of neuronal cell sodium channels, followed by a stimulus pulse. The simulations of the fiber response to such stimulus were performed on an unmyelinated fiber with a computational approach, based on the use of a single cell model, i.e. the Hodgkin and Huxley model, and are compared to the response to commonly used single monophasic stimulus current waveform. Our results show how the ad-hoc designed stimulus current waveform ensures the control of fiber activation in time and the activation/inactivation of fibers with different diameters. This sheds new light on the possibility to develop a new paradigm for selective and controlled neural stimulation. [ABSTRACT FROM AUTHOR]

The expression of pain in males and females involves complex socio-psychological mechanisms. Males may report lower pain to a female experimenter to appear strong, whereas females may report higher pain to a male experimenter to appear weak and to seek protection. However, evidence to support these stereotypes is inconclusive. Individuals who catastrophise about pain rate higher pain than those who do not. How pain catastrophising interacts with the effect of the experimenter's sex on pain reports is yet to be explored. Thus, the aim of this study was to determine whether pain catastrophising moderated the effect of the experimenter's sex on pain reports in healthy males and females. Participants (n=60, 30 males) were assigned to one of four experimental conditions: males tested by male experimenters, males tested by female experimenters, females tested by male experimenters, and females tested by female experimenters. Participants completed the Pain Catastrophising Scale, and then sensitivity to heat and to blunt (pressure-pain threshold) and sharp stimuli was assessed on both forearms, and to high frequency electrical stimulation (HFS) administered to one forearm. Females reported lower pressure-pain thresholds than males irrespective of the experimenters' sex. Females reported lower sharpness ratings to male than female experimenters only when the test stimuli were moderately or intensely sharp. Higher pain catastrophising scores were associated with higher sharpness ratings in females but not males. Additionally, higher pain catastrophising scores were associated with greater temporal summation of pain to HFS, and with lower pressure-pain thresholds in females who were tested by male experimenters. These findings indicate that the experimenters' sex and the participant's pain catastrophising score influence pain reports, particularly in females. Awareness of these psychosocial factors is important in order to interpret pain responses in a meaningful way, especially when females are tested by male experimenters. A greater awareness of sex/gender role biases and their potential interaction with pain catastrophising may help researchers and clinicians to interpret pain reports in meaningful ways. In turn, this may help to improve delivery of treatments for patients with chronic pain. [ABSTRACT FROM AUTHOR]

The relationship of pain sensitivity with pain and disability in low back pain (LBP) is complicated. It has been suggested increased understanding of dynamic quantitative sensory testing (QST) might be useful in increasing understanding of these relationships. This study aimed to create subgroups based on participant responses to dynamic QST, profile these subgroups based on multidimensional variables (including clinical measures of pain and disability, psychological and lifestyle variables and static QST), and investigate the association of subgroup membership with levels of pain intensity, LBP-related disability and disability risk at 12-month follow up. Participants (n=273) with dominant axial chronic non-specific LBP with duration of pain >3 months were included in this study. At baseline, eligible participants completed a self-report questionnaire to collect demographic, clinical, psychological and lifestyle data prior to dynamic and static QST. Dynamic QST measures were conditioned pain modulation (CPM) and temporal summation (TS). At 12-months follow up, clinical data were collected, including pain intensity and LBP-related disability. Sub-groups were formed by cross-tabulation. Analysis was undertaken to profile dynamic QST subgroup on demographic, clinical, psychological, lifestyle and static QST measures. Associations between dynamic QST subgroups and follow-up clinical variables were examined. Based on dynamic QST, participants were allocated into four subgroups; normal CPM and normal TS (n=34, 12.5%); normal CPM and facilitated TS (n=6, 2.2%); impaired CPM and normal TS (n=186, 68.1%); impaired CPM and facilitated TS (n=47, 17.2%). At baseline no differences were demonstrated between subgroups across most clinical variables, or any psychological or lifestyle measures. The two subgroups with impaired CPM were more likely to have a higher number of painful body areas. Cold pain sensitivity was heightened in both the subgroups with facilitated TS. Subgroups did not differ across pain intensity, LBP-related disability and disability risk stratification at follow-up. The profiles of people with axial LBP did not vary significantly across dynamic QST subgroups, save for those in groups with impaired CPM being more likely to have more widespread symptoms and those with facilitated TS having heightened cold pain sensitivity. Further, subgroup membership was not related to future pain and disability. The role of dynamic QST profiles in LBP remains unclear. Further work is required to understand the role of pain sensitivity in LBP. The utility of dynamic QST subgrouping might not be in determining of future disability. Future research might focus on treatment modifying effects of dynamic QST subgroups. [ABSTRACT FROM AUTHOR]

Abstract: When nociceptive stimulation affects a larger body area, pain increases. This effect is called spatial summation of pain (SSp). The aim of this study was to describe SSp as a function of the size or distance of a stimulated area(s) and to test how this function is shaped by the intensity and SSp test paradigm. Thirty-one healthy volunteers participated in a within-subject experiment. Participants were exposed to area-based and distanced-based SSp. For area-based SSp, electrocutaneous noxious stimuli were applied by up to 5 electrodes (5 areas) forming a line-like pattern; for distance-based SSp, the same position and lengths of stimuli were used but only 2 electrodes were stimulated. Each paradigm was repeated using pain of low, moderate, and high intensity. It was found that the pattern of pain intensity followed a logarithmic (power) rather than a linear function. The dynamics of the pain increase were significantly different across pain intensities, with more summation occurring when pain was perceived as low. Results indicated that area-based SSp is more painful than distance-based SSp when low and moderate but not when high pain intensity is induced. Presented findings have important implications for all studies in which the spatial dimension of pain is measured. When the area or separation between nociceptive stimulation increases, pain does not increase linearly and the pattern of the pain increase is a result of the interaction between intensity and the number of nociceptive sites. A power function should be considered when predicting the size of a nociceptive source. [ABSTRACT FROM AUTHOR]

Background: Biopsychosocial factors above and beyond pathoanatomical changes likely contribute to the severity of chronic low back pain. A pro-nociceptive endogenous pain modulatory balance (↓inhibition and ↑facilitation) may be an important contributor to chronic low back pain severity and physical function; however, additional research is needed to address this possibility. The objective of this study was to determine whether quantitative sensory tests of endogenous pain inhibition and facilitation prospectively predict movement-evoked pain and cLBP severity self-reported on a validated questionnaire.Methods: One hundred thirty-four individuals with chronic low back pain were enrolled in this two-session study. During the first study session, temporal summation of mechanical pain and conditioned pain modulation were assessed at the lumbar spine to determine endogenous pain facilitation and inhibition, respectively. One week later, participants returned for a second study session whereby they reported their pain severity and pain interference using the Brief Pain Inventory-Short Form. Movement-evoked pain and physical function capacity were assessed upon completion of the balance, walking, and transition from sit to stand tests of the Short Physical Performance Battery.Results: Temporal summation of mechanical pain, but not conditioned pain modulation, significantly and prospectively predicted greater movement-evoked pain and poorer physical function on the Short Physical Performance Battery. Neither temporal summation nor conditioned pain modulation were significantly related to self-reported pain severity or pain interference on the Brief Pain Inventory-Short Form.Conclusions: Findings suggest that a pro-nociceptive pain modulatory balance characterized by enhanced pain facilitation may be an important driver of movement-evoked pain severity and poor physical function in individuals with chronic low back pain. [ABSTRACT FROM AUTHOR]

At the absolute threshold of vision, Hecht, Shlaer and Pirenne estimate that 5-14 photons are absorbed within a retinal area containing ~500 rods. Other estimates of scotopic threshold vision based on stimuli with different durations and focal areas range up to ~100,000 photons. Given that rod density varies with retinal eccentricity and the magnitude of the intrinsic noise increases with increasing stimulus area and duration, here we determine whether the scotopic threshold estimates with focal stimuli can be extended to full-field stimulation and whether summation explains inter-study differences. We show that full-field threshold vision (~1018 mm2, 10 ms duration) is more sensitive than at absolute threshold, requiring the absorption of ~1000 photons across ~91.96 million rods. A summation model is presented integrating our and published data and using a nominal exposure duration, criterion frequency of seeing, rod density, and retinal area that largely explains the inter-study differences and allows estimation of rods per photon ratio for any stimulus size and duration. The highest signal to noise ratio is defined by a peak rod convergence estimated at 53:4:1:2 (rods:rod bipolar cells:AII amacrine cells:retinal ganglion cells), in line with macaque anatomical estimates that show AII amacrine cells form the bottleneck in the rod pathway to set the scotopic visual limit. Our model estimations that the rods per photon ratio under full-field stimulation is ~3000X higher than at absolute threshold are in accordance with visual summation effects and provide an alternative approach for understanding the limits of scotopic vision. [ABSTRACT FROM AUTHOR]

Background: manual therapy (MT) has been shown to have positive effects in patients with osteoarthritis (OA)-related pain, and its use in clinical settings is recommended. However, the mechanisms of action for how these positive effects occur are not yet well understood. The aim of the present study was to investigate the influence of MT treatment on facilitatory nociception and endogenous pain modulation in patients with knee OA related pain. Methods: Twenty-eight patients with knee OA were included in this study. Pain intensity using the numerical pain rating scale (NPRS), temporal summation (TS), conditioned pain modulation (CPM), and local (knee) and distant (elbow) hyperalgesia through the pressure pain threshold (PPT), were assessed to evaluate the pain modulatory system. Patients underwent four sessions of MT treatments within 3 weeks and were evaluated at the baseline, after the first session and after the fourth session. Results: the MT treatment reduced knee pain after the first session (p = 0.03) and after the fourth session (p = 0.04). TS decreased significantly after the fourth session of MT (p = 0.02), while a significant increase in the CPM assessment was detected after the fourth session (p = 0.05). No significant changes in the PPT over the knee and elbow were found in the follow-ups. Conclusions: The results from our study suggest that MT might be an effective and safe method for improving pain and for decreasing temporal summation. [ABSTRACT FROM AUTHOR]

PASSIVE MUSIC LISTENING HAS SHOWN ITS capacity to soothe pain in several clinical and experimental studies. This phenomenon--known as musicinduced analgesia--could partly be explained by the modulation of pain signals in response to the stimulation of brain and brainstem centers. We hypothesized that music-induced analgesia may involve inhibitory descending pain systems. We assessed pain-related responses to endogenous pain control mechanisms known to depend on descending pain modulation: peak of first pain (PP), temporal summation (TS), and diffuse noxious inhibitory control (DNIC). Twenty-seven healthy participants (14 men, 13 women) were exposed to a conditioned pain modulation paradigm during a 20-minute relaxing music session and a silence condition. Pain was continually measured with a visual analogue scale. Pain ratings were significantly lower with music listening (p < .02). Repeated measures ANOVA indicated significant differences between conditions within PP and TS (p < .05) but not in DNIC. Those findings suggested that music listening could strengthen components of the inhibitory descending pain pathways operating at the dorsal spinal cord level. [ABSTRACT FROM AUTHOR]