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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]

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]

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]

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]

Objectives: The aim of this study was to examine temporal summation (TS) and conditioned pain modulation (CPM) in patients with burning mouth syndrome (BMS) and healthy controls using intra‐epidermal electrical stimulation (IES). Materials and Methods: Twenty‐six female patients with BMS and 27 healthy female controls participated in this study. A single stimulus with electrical stimulation followed by a train of 10 successive stimuli was administered to the right chin of participants in both the BMS and control groups. CPM was evaluated with the changes of TS calculated from the difference in numerical pain scale data between these two test stimuli and the following warm (40°C) and hot (47°C) conditioning stimuli applied at the non‐dominant hand in both the BMS and control groups. Results: TS was present in both the BMS and control groups. CPM in the BMS group was significantly less efficient at the 47°C condition than that in the control group, while no significant difference was observed in the CPM between the BMS and the control groups at the 40°C condition. Conclusion: These findings indicate that BMS is associated with a deficit inhibitory CPM and implicate the involvement of the central nervous system in the pathophysiology of BMS. [ABSTRACT FROM AUTHOR]

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

Introduction This study sought to provide a preliminary assessment of whether spinally mediated afferent hyperactivity (i.e., central sensitization) might contribute to manifestations of overactive bladder syndrome (OAB) in women as indexed by elevated temporal summation of evoked heat pain stimuli. Methods We recruited 20 adult women with OAB who were planning to undergo interventional therapy for OAB with either onabotulinumtoxinA injection or sacral neuromodulation and 23 healthy controls without OAB symptoms to undergo quantitative sensory testing with cutaneous thermal pain temporal summation. The primary study outcome was the degree of temporal summation, as reflected in the magnitude of positive slope of the line fitted to the series of 10 stimuli at the 49°C target temperatures. Linear regression and analysis of covariance were utilized to compare the degree of temporal summation between study groups. Results The standardized slope of temporal summation trials for women with OAB was significantly higher than for controls (β = 3.43, 95% confidence interval = 0.6-6.2, P = 0.017). The adjusted means ±SE of the standardized temporal summation slopes for the full OAB and control groups were 3.0 ± 0.5 (95% confidence interval = 2.0, 4.1) and 1.7 ± 0.5 (95% confidence interval = 0.7, 2.7), respectively. Conclusion In this preliminary study, we demonstrated that women with OAB refractory to primary and secondary therapies exhibited greater thermal cutaneous temporal summation than women without OAB symptoms. This suggests that central sensitization, indexed by temporal summation, may be an underlying factor contributing to OAB in some women. Neurourol. Urodynam. 36:1108-1112, 2017. © 2016 Wiley Periodicals, Inc. [ABSTRACT FROM AUTHOR]

Background Stretching is often used in clinical practice for a variety of purposes, including pain therapy. The possible mechanism behind the effect of stretching remains to be clarified. Aim To investigate whether 4 weeks of unilateral stretching of the calf muscles would affect local and central pain sensitivity. Method This study was a randomized assessor-blinded clinical study. Healthy participants (age 18 to 40) were included and randomized. Participants in the intervention group were instructed to perform 2 stretching exercises targeting the calf muscles; 3 times 30 seconds, 7 days a week for 4 weeks on the dominant leg. Participants in the control group were instructed not to do any stretching for 4 weeks. Pressure pain threshold ( PPT) and temporal summation ( TS) of pressure pain were measured on the stretched calf, the contra-lateral calf, and contra-lateral lower arm using a computerized cuff algometer. Analyses of variance on the per-protocol population (defined as participants that adhered to the protocol) were used to assess group differences in the changes from baseline. Result Forty healthy volunteers were included, of which 34 participants adhered to the protocol (15 intervention group/19 control group). No statistically significant group differences in the changes from baseline were found regarding PPT and TS measurements for the stretched calf, the contra-lateral calf, and the arm. Conclusion Four weeks of regular stretching of the calf muscles does not affect pressure pain sensitivity, suggesting that pressure pain sensitivity is unaffected by stretching in a healthy population. The mechanisms underlying any benefits of regular stretching remain to be explained. [ABSTRACT FROM AUTHOR]

Temporal summation of second pain (TSSP) occurs when painful stimuli are presented repetitively (=0.33 Hz) and results from a C-fibre evoked enhancement (or "wind-up") of the dorsal horn neurons. Based on electrophysiological studies in intact animals, windup is considered a purely central phenomenon. With advancements in functional MRI (fMRI), we can now probe the central mechanisms of this pain response in humans. The aim of this study is to characterize the fMRI responses in the healthy human brainstem and spinal cord that correspond to TSSP. Functional MRI of healthy female adults (N = 15) was conducted while brief, repetitive heat pain stimuli were applied to the right thenar eminence (C6 dermatome), and TSSP (0.33 Hz) and control (0.17 Hz) heat pain paradigms were employed. The stimulus intensity was adjusted to each participant's heat pain sensitivity. Data were analyzed by means of a general linear model, and region-of-interest analyses. As predicted, participants demonstrated significant behavioural summation of pain in the TSSP condition. FMRI results identified enhanced activity in the spinal cord dorsal horn at C6 in response to the TSSP condition. Additionally, multiple areas of the brainstem (RVM and PAG) showed greater responses with the TSSP condition. These results suggest that, in humans, increased pain perception in the TSSP condition is reflected by greater responses in the dorsal horn and in regions known to play a role in the descending modulation of pain, which may modulate the spinal cord response. [ABSTRACT FROM AUTHOR]

Introduction: Central sensitization (CS) can lead to muscle motor dysfunction including fatigue via inducing cortical reorganization in specific brain regions in chronic pain populations, such as patients with lateral elbow pain (LEP)1,2. Aim of this study was to investigate the effect of temporal summation, one aspect of CS on the fatigue of the neck muscles that is the most prominent region affected by CS in LEP. To eliminate other factors that may influence fatigue in LEP, healthy participants were included for this study to investigate specifically the effect of TS on fatigue. Methods: Healthy participants were randomly divided into two groups: an experimental (n = 30) and a control (n = 30) group. In the experimental group, pain was induced at the dominant lateral elbow by means of a temporal summation (TS) protocol via applying pressure at the average level of pressure pain thresholds (PPTs) that was assessed twice. Pain intensity was asked to participants at first, fifth and tenth pulse using a Visual Analog Scale. In the control group, a placebo TS protocol was performed by identifying PPTs once. The muscle fatigue of both sternocleidomastoid and upper trapezius muscles was evaluated during a neck flexor/extensor endurance test using surface electromyography. This was performed before and after the intervention. Results: Evoked TS on the lateral elbow may result in neck muscle fatigue. Process evaluation: Participants had a variety of endurance duration that pushed us to determine window interval during EMG analysis. As participants had different kind of interval, we had to make time normalization using Matlab. [ABSTRACT FROM AUTHOR]

Introduction: Mechanism-based approaches to pain are becoming increasingly popular in recent years. Unfortunately, mechanism-based approaches require assessment using quantitative sensory testing which is rarely available in clinical practice. Therefore, this study compared two clinically applicable test protocols for conditioned pain modulation (CPM) and temporal summation (TS) to a laboratory reference test regarded as a golden standard. Methods: Twenty breast cancer survivors (BCS) experiencing persistent pain were assessed with three different CPM and TS protocols. Two clinically applicable protocols were compared to a reference test. The CPM protocols consisted of a cold water bath or a blood pressure cuff as conditioning stimulus, with pressure pain threshold (PPT) as a test stimulus. TS was applied by using a Von Frey filament or an algometer. The TSA-2 by Medoc (Ramat Yishay, Israel) was used as a reference test for both CPM and TS. Heat was used as stimulus for both reference test protocols. Results: Strong and significant correlation was found for the two clinically applicable CPM test protocols (r > 0.802, p < 0.001). No correlation was found between the CPM reference test and the alternative CPM test protocols. In regard to TS, no correlation was found between the alternative test protocols and the reference TS test protocol. Discussion: No correlation was found between the proposed CPM and TS test protocols and their respective reference test. Process evaluation: Limitations: limited sample size, TS with TSA-2 was performed without the CHEPS thermode however protocol was based upon prior research in healthy individuals and adapted to BCS. [ABSTRACT FROM AUTHOR]

Purpose To quantify the effect of cathode-tube-ray ( CRT) monitor refresh rate on the measurement of the upper limit of complete temporal summation (critical duration) in the peripheral visual field of healthy observers. Methods Contrast thresholds were measured for seven achromatic spot stimuli (diameter 0.48°) of varying duration (nominal values: 10-200 ms) at an eccentricity of 8.8° along the 45°, 135°, 225° and 315° meridians of the visual field in three healthy, psychophysically experienced observers. Stimuli were presented on a CRT display with a refresh rate of 60 and 160 Hz. Contrast thresholds were expressed as contrast energy with stimulus durations being estimated using (1) the sum-of-frames ( SOF) method and (2) Bridgeman's method incorporating measurements of phosphor persistence. Estimates of the critical duration were produced using iterative two-phase regression analysis. Results With stimulus duration expressed as SOF equivalent the critical duration was, on average, 10.6 ms longer with a refresh rate of 60 Hz (mean 45.7 ms, S. D. 10.1 ms) relative to 160 Hz (35.1 ms, S. D. 7.6 ms). When the Bridgeman method was used, minimal differences (1.8 ms) in critical duration values between the two refresh rates (60 Hz: 33.0 ms, S. D. 9.4 ms; 160 Hz: 31.2 ms, S. D. 7.0 ms) were observed. Identical trends were observed in all three subjects. Conclusions Psychophysical measurements of temporal summation are independent of variations in CRT refresh rate when the Bridgeman method, incorporating measured values of phosphor persistence, is used to estimate stimulus duration. This has significant implications for the specification of stimulus duration in psychophysical studies of vision employing conventional display monitors. [ABSTRACT FROM AUTHOR]

Objective Temporal summation ( TS) of pain, conditioned pain modulation ( CPM), and exercise-induced analgesia ( EIA) are often investigated in chronic pain populations as an indicator for enhanced pain facilitation and impaired endogenous pain inhibition, respectively, but interactions are not yet clear both in healthy controls and in chronic pain patients. Therefore, the present double-blind randomized placebo-controlled study evaluates pains cores, TS, and CPM in response to exercise in healthy controls, patients with chronic fatigue syndrome and comorbid fibromyalgia ( CFS/ FM), and patients with rheumatoid arthritis ( RA), both under placebo and paracetamol condition. Methods Fifty-three female volunteers - of which 19 patients with CFS/ FM, 16 patients with RA, and 18 healthy controls - underwent a submaximal exercise test on a bicycle ergometer on 2 different occasions (paracetamol vs. placebo), with an interval of 7 days. Before and after exercise, participants rated pain intensity during TS and CPM. Results Patients with rheumatoid arthritis showed decreased TS after exercise, both after paracetamol and placebo ( P < 0.05). In patients with CFS/ FM, results were less univocal. A nonsignificant decrease in TS was only observed after taking paracetamol. CPM responses to exercise are inconclusive, but seem to worsen after exercise. No adverse effects were seen. Conclusion This study evaluates pain scores, TS, and CPM in response to submaximal exercise in 2 different chronic pain populations and healthy controls. In patients with RA, exercise had positive effects on TS, suggesting normal EIA. In patients with CFS/ FM, these positive effects were only observed after paracetamol and results were inconsistent. [ABSTRACT FROM AUTHOR]

Objectives.- We investigated (1) a possible relationship between the functional activity of the endocannabinoid system and the facilitation of pain processing in migraineurs with medication-overuse headache, and (2) the effect of withdrawal treatment on both. Background.- The endocannabinoid system antinociception effect includes prevention of nociceptive pathways sensitization. The sensitization of the pain pathways has been demonstrated to be pivotal in the development and maintenance of chronic form of migraine, including medication-overuse headache. Methods.- We used the temporal summation threshold of the nociceptive withdrawal reflex to explore the spinal cord pain processing, and the platelet activity of the enzyme fatty acid amide hydrolase to detect the functional state of the endocannabinoid system in 27 medication-overuse headache subjects before and 10 and 60 days after a standard withdrawal treatment and compared results with those of 14 controls. Results.- A significantly reduced temporal summation threshold and increased related pain sensation was found in subjects before withdrawal treatment when compared with controls. A significant fatty acid amide hydrolase activity reduction coupled with a significant improvement (reduction) in facilitation of spinal cord pain processing (increase in temporal summation threshold and reduction in related pain sensation) was found in medication-overuse headache subjects at both 10 and 60 days after withdrawal treatment when compared with medication-overuse headache subjects before withdrawal treatment. Conclusions.- We demonstrated a marked facilitation in spinal cord pain processing in medication-overuse headache before withdrawal treatment when compared with controls. Furthermore, the acute reduction of the fatty acid amide hydrolase activity coupled with a reduction of the facilitation in pain processing immediately (10 days) after withdrawal treatment and its persistence 60 days after withdrawal treatment could represent the consequence of a mechanism devoted to acutely reduce the degradation of endocannabinoids and aimed to increase the activity of the endocannabinoid system that results in an antinociceptive effect. [ABSTRACT FROM AUTHOR]

Abstract: Nitric-oxide donor glyceryl-trinitrate (GTN) modulates cerebral and spinal regions that are involved in migraine and pain processing. We hypothesized that in migraineurs, the susceptibility to develop a migraine attack after GTN administration should parallel with an high sensitivity to GTN-induced change in the pain processing at spinal level. We used the temporal summation threshold (TST) of the lower limb nociceptive withdrawal reflex (NWR) and the related pain sensation to study in parallel the time-course of the effect of the GTN administration on the pain processing at spinal level in migraine and healthy subjects. Twenty-eight (21 F; 7M; mean age 34.2±8.2) migraine and 15 (11 F; 4M; mean age 35.9±8.9) healthy subjects were recruited in a double-blind, placebo-controlled, cross-over trial. Neurophysiological examinations were carried out before (baseline) and 30′, 60′, 120′, 180′ and 240′ after GTN (0.9mg sublingual) or placebo administration during two different sessions. In migraineurs, GTN administration was associated to a significant facilitation in temporal summation of pain (reduced TST and increased painful sensation) 60′, 120′ and 180′ after drug intake when compared to baseline, to placebo condition and to controls after GTN intake. Furthermore, in migraineurs who developed migraine after GTN, a significant facilitation in temporal summation of pain was detected 60′, 120′ and 180′ after drug intake when compared to patients without clinical response. In migraineurs the susceptibility to develop migraine attack after GTN administration seems to be a specific trait of a subgroup of patients linked to a supersensitivity of the pain system to GTN. [Copyright &y& Elsevier]

Abstract: Eccentric jaw exercises has been known to cause muscle soreness but no studies have so far examined to what extent temporal summation mechanisms within the exercised muscles are changed. The purpose of the present study was to investigate the effects of an eccentric biting exercise on the temporal summation, mechanical pressure sensitivity and jaw muscle activity. A total of 15 healthy men participated in a two-session-experiment: In one session, they performed 30min controlled eccentric jaw exercise and the other session served as a no-exercise control. Soreness sensations at rest and during maximal biting, pressure pain thresholds (PPTs) and electromyographic (EMG) activity during maximal jaw biting were recorded before (baseline), immediately after (Post-task), and 1day after the exercise (1-day-after). The temporal summation ratio using intra-muscular electrical stimulation of the masseter was investigated at baseline and at 1-day-after. The eccentric jaw exercise was associated with significant increases in soreness sensation and decreased PPTs at Post-task and at 1-day-after. The EMG activity and biting force did not change. The summation ratio was significantly decreased at 1-day-after in both sessions. The present findings demonstrate that eccentric jaw exercise does not induce detectable changes in temporal summation. However, the summation ratio may have clinical utility to differentiate the location of sensitization. [Copyright &y& Elsevier]

( Headache 2010;50:403-412) Objective.— To examine effects of stress on noxious inhibition and temporal summation (TS) in tension-type headache. Background.— Stress is the most commonly reported trigger of a chronic tension-type headache (CTH) episode; however, the mechanisms underlying this are unclear. Stress affects pain processing throughout the central nervous system, including, potentially, mechanisms of TS and diffuse noxious inhibitory controls (DNIC), both of which may be abnormal in CTH sufferers (CTH-S). No studies have examined TS of pressure pain or DNIC of TS in CTH-S to date. Similarly, effects of stress on TS or DNIC of TS have not been reported in healthy subjects or CTH-S to date. Methods.— The present study measured TS and DNIC of TS in CTH-S and healthy controls (CNT) exposed to an hour-long stressful mental task, and in CTH-S exposed to an hour-long neutral condition. TS was elicited at finger and shoulder via 10 pulses from a pressure algometer, applied before and during stimulation from an occlusion cuff at painful intensity. Results.— Algometer pain ratings increased more in the CTH compared with the CNT group, and were inhibited during occlusion cuff more in the CNT compared with CTH groups. Task effects on TS or DNIC were not significant. Conclusions.— The results indicate increased TS to pressure pain and impaired DNIC of TS in CTH-S. Stress does not appear to aggravate abnormal TS or DNIC mechanisms in CTH-S. [ABSTRACT FROM AUTHOR]

Abstract: Nerve growth factor (NGF) has a key role in the generation and potentiation of pain. Its centrally sensitizing effects may facilitate pain responses to noxious stimulus. This study assessed (1) the influence of NGF on delayed onset muscle soreness (DOMS) in shoulder muscles; and (2) the temporal summation of pressure pain during hyperalgesia induced by NGF and DOMS. In a blinded design, 10 healthy subjects were injected with NGF in the trapezius muscle on one side and with isotonic saline on the contralateral side as control. The subjects undertook shoulder eccentric exercise to induce DOMS in the shoulder muscles 3h after the injections. The soreness intensity to muscle contraction, pressure pain thresholds (PPT), and pain intensity to sequential stimuli (i.e. temporal summation at 1 and 30s inter-stimulus interval (ISI)) were assessed before injections – 3, 24h, and 4, 7, and 21 days after injections. The soreness intensity to muscle contraction significantly increased at 3 and 24h in both shoulders (P <0.05) and went back to baseline levels at day 7. The same development was seen in PPT as reduced thresholds (P <0.05). The NGF injected side had higher pain ratings during temporal summation at 1s ISI compared with the contralateral side 24h after injections. Intramuscular administration of NGF intensified the DOMS responses, evoking facilitated temporal summation. Central as well as peripheral sensitization mechanisms may play a role in the facilitation. [Copyright &y& Elsevier]

Abstract: Chronic pain patients often suffer from widespread and long lasting pain. The integrative effect of combined spatial and temporal summation on pain intensity has not been quantitatively tested. The present study was designed to investigate: (1) if the size of the stimulation area would facilitate the temporal summation of pain to repetitive pressure stimulation, and (2) if temporal summation is effective when stimulating separated sites, repetitively. Twenty healthy male subjects participated in this study. The test sites were located on the bilateral upper trapezius and tibialis anterior muscles. The ten stimuli (each with a duration of 1s) were applied to a single site at three inter-stimulus intervals (ISI: 1, 5, 30s) using five different probe sizes (0.5, 1, 2, 4 and 8cm2). The stimulation intensity was equal to the pressure pain threshold (PPT) determined for each probe size. Similar repetitive stimulations at two inter-stimulus intervals (5s and 30s) using two sizes of probes (0.5cm2 and 2cm2) were applied to ten separate sites. The PPT at the trapezius muscle decreased significantly with the increase in stimulus area from 0.5cm2 to 8cm2 (P <0.001) due to spatial summation. Temporal summation of pain was evoked by repetitive pressure stimuli on the same site for all ISI and was more pronounced at 5s and 30s ISI with larger probe areas (2, 4, and 8cm2) compared to smaller probe areas. There was no temporal summation of pain to stimuli with ISI 5 and 30s when stimulating the separated sites. The current study indicated that spatial summation facilitated the temporal summation of pain for stimuli given at 5s and 30s ISI. The combination of temporal and spatial integration of nociceptive input facilitates the pain intensity, suggesting that temporal summation is clinically relevant in conditions with widespread pain. [Copyright &y& Elsevier]

Abstract: Temporal summation of “second pain” (TSSP) is the result of C-fiber-evoked responses of dorsal-horn neurons, termed “windup”. This phenomenon is dependent on stimulus frequency (⩾0.33Hz) and relevant for central sensitization as well as chronic pain. Whereas, our previous functional magnetic resonance imaging (fMRI) study characterized neural correlates of TSSP in 11 healthy volunteers, the present study was designed to compare brain responses associated with TSSP across these healthy participants and 13 fibromyalgia (FM) patients. Volume-of-interest analysis was used to assess TSSP-related brain activation. All participants underwent fMRI-scanning during repetitive heat pulses at 0.33Hz and 0.17Hz to the right foot. Stimulus intensities were adjusted to each individual’s heat sensitivity to achieve comparable TSSP-ratings of moderate pain in all subjects. Experimental pain ratings showed robust TSSP during 0.33Hz but not 0.17Hz stimuli. When stimulus strength was adjusted to induce equivalent levels of TSSP, no differences in activation of pain-related brain regions occurred across NC and FM groups. Subsequently, the fMRI-data of both groups were combined to increase the power of our statistical comparisons. fMRI-statistical maps identified several brain regions with stimulus and frequency dependent activation consistent with TSSP, including ipsilateral and contralateral thalamus, medial thalamus, S1, bilateral S2, mid- and posterior insula, rostral and mid-anterior cingulate cortex. However, the stimulus temperatures necessary to evoke equivalent levels of TSSP and corresponding brain activity were less in FM patients. These results suggest that enhanced neural mechanisms of TSSP in FM are reflected at all pain related brain areas, including posterior thalamus, and are not the result of selective enhancement at cortical levels. [Copyright &y& Elsevier]

Background: Muscle pain is a major clinical problem but the underlying mechanisms and its pharmacological modulation need further investigation. This study on 15 volunteers evaluates if two experimental muscle pain models are sensitive to µ-receptor agonists and to an N-methyl-D-aspartate (NMDA)-receptor antagonist. Methods: In the left tibialis anterior, intramuscular electrical (IMES) pain thresholds were determined for single (SPTmuscle ) and five (RPTmuscle ) repeated stimuli. Also pain to suprathreshold stimulation at 150% of RPTmuscle , 10 s, was assessed on a visual analog scale (VAS) as AUCimes (area under the VAS curve). In the right TA muscle, pain intensity on infusion of 0.5 ml of hypertonic saline, 5% (AUCsaline ) and pain distribution indicated as local and referred were evaluated. Pain variables were assessed before, during and after intravenous infusions of morphine (10 µg kg-1 min-1 , 10 min), alfentanil (target-controlled infusion, plasma concentration; 60 ng ml-1 , 60 min) and ketamine (10 µg kg-1 min-1 , 60 min). All data were normalized to baseline pain values (before drug infusions were initiated) and compared with placebo (midazolam, 2 µg kg-1 min-1 , 10 min). Results: SPTmuscle increased (log mean values ± SD, mA) with morphine (0.11 ± 0.17, P < 0.05), alfentanil (0.28 ± 0.24, P < 0.001) and ketamine (0.19 ± 0.18, P < 0.01) as compared with placebo (-0.03 ± 0.12). Alfentanil and ketamine also increased RPTmuscle (0.25 ± 0.21, P < 0.01 and 0.21 ± 0.19, P < 0.05, respectively) as compared with placebo (0.00 ± 0.17). Pain to IMES (AUCimes ) was reduced (median values [25th-75th percentiles], cm × s) by alfentanil and ketamine (-19.7 [-14.6 – -29.6] and-12.8 [-8.3 – -27.8], P < 0.05, respectively) vs. placebo (-0.8 [1.6 – -12.3]). Similar drug effects were seen when pain to infusion of hypertonic saline (AUCsaline ) was assessed (alfentanil:-388 [-99 – -677] and ketamine:-326 [-227 – -573], P < 0.05 compared with placebo: 150 [449–-240]). Ketamine also reduced the size of the local pain area (-58.4 [-21.2 – -176.1], < 0.05) as compared with placebo (-0.4 [70.6 – -13.4]). The frequency of referred pain was also lower when ketamine was given (3/13, P < 0.05) vs. placebo (9/14). Conclusion: The study demonstrates that experimental muscle pain induced in humans by electrical stimulation and infusion of hypertonic saline is sensitive to pharmacological modulation similar to preclinical animal tests and clinical trials. The data suggest that these models can be valuable tools in analgesic drug development. [ABSTRACT FROM AUTHOR]

Abstract: Many neuropathic pain conditions are characterized by abnormal responses to noxious or innocuous mechanical stimulation, including wind-up pain. Whereas previous brain imaging studies have explored the cerebral correlates of hyperalgesia and allodynia, no studies are available on mechanical-induced wind-up pain in neuropathic pain patients. We therefore used positron emission tomography (PET) to investigate the cerebral response pattern of mechanical wind-up pain in a homogenous group of 10 neuropathic pain patients with long-standing postherniotomy pain in the groin area. Patients were scanned in the following conditions: (1) rest; (2) wind-up pain, induced by 2Hz von Frey stimulation in the painful area; (3) non-painful 2Hz von Frey stimulation in the homologous contralateral area and (4) tonic pressure pain in the homologous contralateral area. A direct comparison between wind-up pain and non-painful von Frey stimulation revealed that the former more strongly activated contralateral secondary somatosensory cortex, insula, anterior cingulate cortex, right dorsolateral prefrontal cortex, thalamus and cerebellum. In addition, wind-up pain also activated the sublenticular extended amygdala (SLEA) and the brain stem. A direct comparison between wind-up pain and pressure pain revealed that both activated a largely overlapping network. Since no de novo brain areas were activated by wind-up pain, our data suggest that the processes specific to wind-up pain do not occur at the cerebral level. [Copyright &y& Elsevier]