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Lars Arendtnielsen - One of the best experts on this subject based on the ideXlab platform.
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the inhibitory effect of conditioned pain modulation on Temporal Summation in low back pain patients
Scandinavian Journal of Pain, 2021Co-Authors: Soren Oneill, Lars Arendtnielsen, Liam Holm, Johanne Brinch Filtenborg, Casper Glissmann NimAbstract:OBJECTIVES The literature on conditioned pain modulation (CPM) is inconclusive in relation to low-back pain and it is unclear how CPM affects Temporal Summation as a proxy of central pain integration. The aim of this study was to examine whether the CPM effect would be different on pain induced by Temporal Summation than single stimuli in a group of low back pain patients. METHODS A total of 149 low-back pain patients were included. CPM was examined using single, repeated and Temporal Summation (repeated-single difference) of mechanical pressure pain as test stimuli at an individualized, fixed supra-pain-threshold force, before and after 2 min of cold pressor test (0-2 degrees Celsius). Participants were categorized as CPM responders or non-responders according to three different criteria: simple (any pain inhibition), strict (pain inhibition of more than 10VAS) and reversed (pain inhibition or facilitation of less than 10VAS). Clinical data on back pain was collected for correlation and descriptive purposes. RESULTS Significant modulation was observed for all three test stimuli. Effects sizes were comparable in relative terms, but repeated pressure pain modulation was greater in absolute terms. No correlations to clinical data were observed, for any measure. CONCLUSIONS The current data suggests that repeated pressure pain may be better suited as the CPM test stimuli, than single pressure pain and Temporal Summation of pressure pain, as the CPM effect in absolute terms was greater. Employing Temporal Summation as the test stimulus in a CPM paradigm may be more sensitive than a single test stimulus.
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conditioning pain modulation reduces pain only during the first stimulation of the Temporal Summation of pain paradigm in healthy participants
European Journal of Pain, 2019Co-Authors: Sinead Holden, Kristian Kjær Petersen, Lars Arendtnielsen, Thomas GravennielsenAbstract:Background Pro-nociceptive and anti-nociceptive mechanisms are commonly assessed in clinical and experimental pain studies, but their potential interaction is not well understood. Objectives Investigate the effect of conditioning pain modulation (CPM) on Temporal Summation of pain (TSP). Methods Twenty healthy participants underwent cuff algometry assessment on the lower legs to establish the pressure pain tolerance threshold (PTT). For the TSP assessment, ten stimuli at the level of the PTT were delivered by computerised cuff inflations (1-s stimulation, 1-s break) while participants rated pain intensity on a 10-cm electronic visual analogue scale (VAS). This TSP paradigm was then repeated with a simultaneous conditioning stimulus induced by a cuff on the contralateral leg, inflated to a constant pressure corresponding to 30% (mild), 70% (moderate) or 100% (severe) of the PTT. These were assessed in a randomised order, with a fifteen-minute break between tests. A final TSP test without conditioning was reassessed at the end (post-recording). Results An interaction between stimuli (1-10) and repetition (p 0.05). Conclusions The current study indicates that mild to severe stimuli administered by cuff algometry does not modulate Summation effect of Temporal Summation of pain, which could indicate that pain facilitatory mechanisms are more potent compared with pain inhibitory mechanisms. Significance Current knowledge on the interaction effect of pro and anti-nociceptive paradigms are the lacking. The current study indicates that conditioning pain modulation does not modulate the Summation effect of Temporal Summation of pain, when evaluated by computerized pressure algometry. This finding was independent of the mild, moderate and severe painful conditioning intensities.
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assessment of musculoskeletal pain sensitivity and Temporal Summation by cuff pressure algometry a reliability study
Pain, 2015Co-Authors: Thomas Gravennielsen, Henrik Bjarke Vaegter, Gitte Handberg, Sara Finocchietti, Lars ArendtnielsenAbstract:Chronic musculoskeletal pain is linked with sensitization, and standardized methods for assessment are needed. This study investigated (1) the test-retest reliability of computer-controlled cuff-pressure algometry (pain thresholds and Temporal pain Summation) on the arm and leg and (2) conditioned pain modulation (CPM) assessed by cuff algometry. The influences of age and gender were evaluated. On 2 different days, cuff pain threshold (cPPT), cuff pain tolerance (cPTT), and Temporal Summation of pain (TSP) by visual analog scale scores to 10 repeated cuff stimulations at cPTT intensity, as well as pressure pain threshold with handheld pressure algometry, were assessed in 136 healthy subjects. In one session, cuff pain sensitivity was also assessed before and after cold pressor-induced CPM. Good-to-excellent intraclass correlations (0.60-0.90) were demonstrated for manual and cuff algometry, and no systematic bias between sessions was found for cPPT, cPTT, and TSP on the leg and for cPTT and TSP on the arm. Cuff pressure pain threshold and cPTT were higher in men compared with women (P < 0.05). Middle-aged subjects had higher pressure pain threshold, but lower cPPT and cPTT, compared with younger subjects (P < 0.05). Temporal Summation of pain was increased in women compared with men (P < 0.05). Cuff algometry was sensitive to CPM demonstrated as increased cPPT and cPTT and reduced TSP (P < 0.05). Reliability and sensitivity of computer-controlled cuff algometry for pain assessment is comparable with manual pressure algometry and constitutes a user-independent method for assessment of pain. Difference in age-related pain sensitivity between manual and cuff algometry should be further investigated.
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widespread pain hypersensitivity and facilitated Temporal Summation of deep tissue pain in whiplash associated disorder an explorative study of women
Journal of Rehabilitation Medicine, 2012Co-Authors: Dag Lemming, Thomas Gravennielsen, Lars Arendtnielsen, Jan Sorensen, Bjorn GerdleAbstract:Objective: Widespread deep tissue pain hyperalgesia was evaluated in women with chronic whiplash associated disorder (n=25) and controls (n=10) using computerized cuff pressure algometry and hypertonic saline infusion. Methods: A pneumatic double-chamber cuff was placed around: (i) the arm and (ii) the leg. Cuff inflation rate was constant and the pain intensity was registered continuously on a visual analogue scale (VAS); thresholds of detection and tolerance were extracted. For assessment of spatial Summation the protocol was repeated with a single-chamber cuff inflated around the leg. Temporal Summation of pain was assessed from the leg with constant cuff pressure stimulation at 2 different pressure intensities for 10 min. Hypertonic saline was infused in the tibialis anterior muscle. Results: Cuff pressure pain thresholds were lower in subjects with whiplash associated disorder compared with controls (pless than0.05). Tonic pressure stimulation evoked higher maximal VAS and larger areas under the VAS curve in subjects with whiplash associated disorder compared with controls (pless than0.05). The pain threshold and tolerance were higher during single cuff than double cuff stimulation. The area under the VAS curve after intramuscular saline infusion was larger in whiplash associated disorder (pless than0.05). Conclusion: The results indicated widespread hyperalgesia in chronic whiplash associated disorder and facilitated Temporal Summation outside the primary pain area, suggesting involvement of central sensitization.
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a translational study of the effects of ketamine and pregabalin on Temporal Summation of experimental pain
Regional Anesthesia and Pain Medicine, 2011Co-Authors: Lars Arendtnielsen, Camilla Staahl, Trevor S Smart, Heikki Mansikka, Huw Rees, Keith Tan, Russel Monhemius, Rie Suzuki, Asbjorn Mohr DrewesAbstract:Background and Objectives: Central sensitization is often seen in chronic pain. A relevant and potent mechanism of central sensitization is the central integration of nociceptive impulses. Temporal Summation in humans and the wind-up process in animals share common features of central integration. This preclinical and clinical translational study investigated the effect of ketamine and pregabalin on Temporal Summation (TS) and wind-up of wide dynamic range (WDR) neurons of nociceptive electrical stimuli in healthy volunteers and rats. Methods: This 3-way crossover study included healthy male volunteers (n = 18) receiving 3 doses of 300 mg pregabalin (orally) over 2 days, ketamine (intravenous loading dose 0.5 mg/kg followed by 9 μg/kg per minute for 20 mins) on the first day, or placebo. The pain detection thresholds to repetitive electrical cutaneous and suprathreshold responses stimulation were assessed. In male Sprague-Dawley rats (n = 30), WDR neuron recordings after electrical stimulation were obtained before and after 15 minutes of intravenous infusion pregabalin (0.127, 0.42, and 1.27 mg/kg per minute) and ketamine (0.006, 0.02, 0.06, and 0.2 mg/kg per minute). Results: In the human study, ketamine compared with placebo significantly increased the TS pain detection threshold (P Conclusions: It was shown that TS shares common features with wind-up of WDR neurons and that pregabalin does not affect this component of central sensitization.
Thomas Gravennielsen - One of the best experts on this subject based on the ideXlab platform.
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conditioning pain modulation reduces pain only during the first stimulation of the Temporal Summation of pain paradigm in healthy participants
European Journal of Pain, 2019Co-Authors: Sinead Holden, Kristian Kjær Petersen, Lars Arendtnielsen, Thomas GravennielsenAbstract:Background Pro-nociceptive and anti-nociceptive mechanisms are commonly assessed in clinical and experimental pain studies, but their potential interaction is not well understood. Objectives Investigate the effect of conditioning pain modulation (CPM) on Temporal Summation of pain (TSP). Methods Twenty healthy participants underwent cuff algometry assessment on the lower legs to establish the pressure pain tolerance threshold (PTT). For the TSP assessment, ten stimuli at the level of the PTT were delivered by computerised cuff inflations (1-s stimulation, 1-s break) while participants rated pain intensity on a 10-cm electronic visual analogue scale (VAS). This TSP paradigm was then repeated with a simultaneous conditioning stimulus induced by a cuff on the contralateral leg, inflated to a constant pressure corresponding to 30% (mild), 70% (moderate) or 100% (severe) of the PTT. These were assessed in a randomised order, with a fifteen-minute break between tests. A final TSP test without conditioning was reassessed at the end (post-recording). Results An interaction between stimuli (1-10) and repetition (p 0.05). Conclusions The current study indicates that mild to severe stimuli administered by cuff algometry does not modulate Summation effect of Temporal Summation of pain, which could indicate that pain facilitatory mechanisms are more potent compared with pain inhibitory mechanisms. Significance Current knowledge on the interaction effect of pro and anti-nociceptive paradigms are the lacking. The current study indicates that conditioning pain modulation does not modulate the Summation effect of Temporal Summation of pain, when evaluated by computerized pressure algometry. This finding was independent of the mild, moderate and severe painful conditioning intensities.
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assessment of musculoskeletal pain sensitivity and Temporal Summation by cuff pressure algometry a reliability study
Pain, 2015Co-Authors: Thomas Gravennielsen, Henrik Bjarke Vaegter, Gitte Handberg, Sara Finocchietti, Lars ArendtnielsenAbstract:Chronic musculoskeletal pain is linked with sensitization, and standardized methods for assessment are needed. This study investigated (1) the test-retest reliability of computer-controlled cuff-pressure algometry (pain thresholds and Temporal pain Summation) on the arm and leg and (2) conditioned pain modulation (CPM) assessed by cuff algometry. The influences of age and gender were evaluated. On 2 different days, cuff pain threshold (cPPT), cuff pain tolerance (cPTT), and Temporal Summation of pain (TSP) by visual analog scale scores to 10 repeated cuff stimulations at cPTT intensity, as well as pressure pain threshold with handheld pressure algometry, were assessed in 136 healthy subjects. In one session, cuff pain sensitivity was also assessed before and after cold pressor-induced CPM. Good-to-excellent intraclass correlations (0.60-0.90) were demonstrated for manual and cuff algometry, and no systematic bias between sessions was found for cPPT, cPTT, and TSP on the leg and for cPTT and TSP on the arm. Cuff pressure pain threshold and cPTT were higher in men compared with women (P < 0.05). Middle-aged subjects had higher pressure pain threshold, but lower cPPT and cPTT, compared with younger subjects (P < 0.05). Temporal Summation of pain was increased in women compared with men (P < 0.05). Cuff algometry was sensitive to CPM demonstrated as increased cPPT and cPTT and reduced TSP (P < 0.05). Reliability and sensitivity of computer-controlled cuff algometry for pain assessment is comparable with manual pressure algometry and constitutes a user-independent method for assessment of pain. Difference in age-related pain sensitivity between manual and cuff algometry should be further investigated.
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isometric exercises reduce Temporal Summation of pressure pain in humans
European Journal of Pain, 2015Co-Authors: Gitte Handberg, Henrik Bjarke Vaegter, Thomas GravennielsenAbstract:Background Aerobic and isometric exercises are known to decrease pain sensitivity. The effect of different types of exercise on central mechanisms such as Temporal Summation of pain (TSP) is less clear. This study hypothesized that both aerobic and isometric exercises would increase pressure pain tolerance (PTT) and reduce TSP with greater effects after higher-intensity exercises. Methods One hundred thirty-six healthy subjects (18–65 years; 68 women) participated in two randomized crossover experiments with trials on two different days. PTT and TSP were assessed before and after bicycling and a non-exercise condition (experiment 1), and after low- and high-intensity bicycling and low- and high-intensity isometric arm and leg exercises with the dominant arm/leg (experiment 2). PTT and TSP were assessed before and after each exercise condition on the non-dominant arm and leg by computer-controlled cuff algometry. TSP was assessed by visual analogue scale (VAS) scores of the pain intensity during sequential cuff-pressure stimulation at the pain tolerance intensity related to that specific time point. Results In experiment 1, bicycling, but not the non-exercise condition, slightly increased PTT when assessed at the leg (p < 0.05). In experiment 2, isometric arm and leg exercises increased PTT and reduced VAS scores to sequential stimulation at the arm and leg (p < 0.05). No systematic difference was found between low- and high-intensity exercises. Conclusions Different manifestations of hypoalgesia between aerobic and isometric exercises were found. Isometric exercises reduced Temporal Summation illustrating the potential for exercise as a rehabilitation procedure also targeting the central mechanisms.
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repeated intramuscular injections of nerve growth factor induced progressive muscle hyperalgesia facilitated Temporal Summation and expanded pain areas
Pain, 2013Co-Authors: Koei Hayashi, Shinichiro Shiozawa, Noriyuki Ozaki, Kazue Mizumura, Thomas GravennielsenAbstract:Intramuscular injection of nerve growth factor (NGF) is known to induce deep-tissue mechanical hyperalgesia. In this study it was hypothesised that daily intramuscular injections of NGF produce a progressive manifestation of soreness, mechanical hyperalgesia, and Temporal Summation of pain. In a double-blind placebo-controlled design, 12 healthy subjects were injected on 3 days with NGF into the tibialis anterior muscle and with isotonic saline on the contralateral side. Assessments were performed before and after the injections on days 0, 1, and 2, and repeated on days 3, 6, and 10. The self-perceived muscle soreness was assessed on a Likert scale. Computer-controlled pressure algometry was used to assess the pressure pain thresholds (PPTs). Temporal Summation of pain after repeated pressure stimulations was assessed by computer-controlled pressure algometry. The pain distribution following painful pressure stimulation was also recorded. Compared with baseline and isotonic saline, the NGF injections caused (P<0.05): (1) progressively increasing soreness scores from 3 hours after the first injection until day 2, after which it remained increased; (2) decreased PPTs at days 1 to 3; (3) facilitated Temporal Summation of pressure pain at days 1 to 10; and (4) enlarged pressure-induced pain area after the injection on day 1 to day 6. The daily injections of NGF produced a progressive manifestation of muscle soreness, mechanical hyperalgesia, Temporal Summation of pressure pain, and pressure-induced pain distribution. These data illustrate that the prolonged NGF application affects peripheral and central mechanisms and may reflect process in musculoskeletal pain conditions.
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repeated intramuscular injections of nerve growth factor induced progressive muscle hyperalgesia facilitated Temporal Summation and expanded pain areas
Pain, 2013Co-Authors: Koei Hayashi, Shinichiro Shiozawa, Noriyuki Ozaki, Kazue Mizumura, Thomas GravennielsenAbstract:Abstract Intramuscular injection of nerve growth factor (NGF) is known to induce deep-tissue mechanical hyperalgesia. In this study it was hypothesised that daily intramuscular injections of NGF produce a progressive manifestation of soreness, mechanical hyperalgesia, and Temporal Summation of pain. In a double-blind placebo-controlled design, 12 healthy subjects were injected on 3 days with NGF into the tibialis anterior muscle and with isotonic saline on the contralateral side. Assessments were performed before and after the injections on days 0, 1, and 2, and repeated on days 3, 6, and 10. The self-perceived muscle soreness was assessed on a Likert scale. Computer-controlled pressure algometry was used to assess the pressure pain thresholds (PPTs). Temporal Summation of pain after repeated pressure stimulations was assessed by computer-controlled pressure algometry. The pain distribution following painful pressure stimulation was also recorded. Compared with baseline and isotonic saline, the NGF injections caused (P
Donald D Price - One of the best experts on this subject based on the ideXlab platform.
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effects of the n methyl d aspartate receptor on Temporal Summation of second pain wind up in irritable bowel syndrome
The Journal of Pain, 2011Co-Authors: Donald D Price, Qiqi Zhou, Christopher S Callam, Michael A Woodruff, Nicholas G VerneAbstract:Abstract Irritable bowel syndrome (IBS) is a common gastrointestinal disorder in which the pathophysiological mechanisms of the pain and hypersensitivity are not well understood. IBS patients frequently complain of pain in body regions somatotopically distinct from the gut, suggesting that central hyperalgesic mechanisms may be involved. In the current study, during the wind-up testing session, a series of 6 heat pulses were presented with an interstimulus interval (ISI) of 3 seconds. Following the 1st, 3rd, and 6th thermal stimuli, subjects were asked to rate the late thermal sensation or second pain. IBS patients who demonstrated Temporal Summation of pain (TSSP) then received dextromethorphan and placebo in a randomized, double-blind, fashion to block wind-up. The results showed: 1) a subset of IBS patients, but not controls, showed TSSP in response to a series of noxious heat pulses; and 2) TSSP was blocked by administration of dextromethorphan, an NMDA receptor antagonist. In summary, these findings further elucidate mechanisms of somatic hypersensitivity in a subset of IBS patients. Our results also support an etiologic basis for abnormal NMDA receptor mechanisms in some IBS patients. Future studies are needed to determine if NMDA receptor antagonists may be used to treat IBS patients. Perspective This study evaluates Temporal Summation of second pain in a subset of IBS patients that is blocked by Dextromethorphan, an NMDA receptor antagonist. Theses results could lead to the use of an NMDA receptor antagonist in the treatment of pain in a subset of IBS patients.
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supra threshold scaling Temporal Summation and after sensation relationships to each other and anxiety fear
Journal of Pain Research, 2010Co-Authors: Michael E Robinson, Donald D Price, Joel E Bialosky, Mark D Bishop, Steven Z GeorgeAbstract:This study investigated the relationship of thermal pain testing from three types of quantitative sensory testing (ie, supra-threshold stimulus response scaling, Temporal Summation, and after-sensation) at three anatomical sites (ie, upper extremity, lower extremity, and trunk). Pain ratings from these procedures were also compared with common psychological measures previously shown to be related to experimental pain responses and consistent with fear-avoidance models of pain. Results indicated that supra-threshold stimulus response scaling, Temporal Summation, and after-sensation, were significantly related to each other. The site of stimulation was also an important factor, with the trunk site showing the highest sensitivity in all three quantitative sensory testing procedures. Supra-threshold response measures were highly related to measures of fear of pain and anxiety sensitivity for all stimulation sites. For Temporal Summation and after-sensation, only the trunk site was significantly related to anxiety sensitivity, and fear of pain, respectively. Results suggest the importance of considering site of stimulation when designing and comparing studies. Furthermore, psychological influence on quantitative sensory testing is also of importance when designing and comparing studies. Although there was some variation by site of stimulation, fear of pain and anxiety sensitivity had consistent influences on pain ratings.
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cutaneous c fiber pain abnormalities of fibromyalgia patients are specifically related to Temporal Summation
Pain, 2008Co-Authors: Roland Staud, Michael E Robinson, Courtney E Bovee, Donald D PriceAbstract:Abstract Temporal Summation of “second pain” (TSSP) is considered to be the result of C-fiber-evoked responses of dorsal horn neurons, termed ‘windup’. TSSP is dependent on stimulus frequency (⩾0.33 Hz) and is relevant for central sensitization and chronic pain. We have previously shown that compared to normal controls (NC), fibromyalgia (FM) subjects show abnormal TSSP, requiring lower stimulus intensities/frequencies to achieve similar TSSP. However, it is unknown whether abnormal TSSP in FM is influenced by peripheral sensitization of C-fiber nociceptors and/or bias in pain ratings. Thus, we evaluated 14 FM subjects and 19 NC with pain threshold tests to selective C-fiber stimulation, 30 s heat stimuli, and repetitive brief (1.5 s) heat pulses at 0.33 Hz using a contact heat stimulator (CHEPS). The intensity of heat pulses was varied to achieve maximal TSSP ratings of 45 ± 10 (numerical pain scale 0–100) in both FM and NC groups. We found that NC and FM subjects had similar pain thresholds to C-fiber stimulation and yet FM subjects required lower heat pulse temperatures to generate the same magnitudes of TSSP (p
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brain activity related to Temporal Summation of c fiber evoked pain
Pain, 2007Co-Authors: Roland Staud, Michael E Robinson, Jason G Craggs, William M Perlstein, Donald D PriceAbstract:Temporal Summation of "second pain" (TSSP) is considered to be the result of C-fiber-evoked responses of dorsal horn neurons, termed 'windup'. This phenomenon is dependent on stimulus frequency (0.33 Hz) and relevant for central sensitization and chronic pain. Previous brain imaging studies have only been used to characterize neural correlates of second pain but not its Temporal Summation. We utilized functional magnetic resonance imaging (fMRI) in healthy volunteers to measure brain responses associated with TSSP. Region of interest analysis was used to assess TSSP related brain activation. Eleven pain-free normal subjects underwent fMRI scanning during repetitive heat pulses to the right foot at 0.33 and 0.17 Hz. Stimulus intensities were adjusted to each individual's heat sensitivity to achieve comparable TSSP ratings of moderate pain in all subjects. As predicted, experimental pain ratings showed robust TSSP during 0.33 Hz but not 0.17 Hz stimuli. fMRI statistical maps identified several brain regions with stimulus and frequency dependent activation consistent with TSSP, including contralateral thalamus (THAL), S1, bilateral S2, anterior and posterior insula (INS), mid-anterior cingulate cortex (ACC), and supplemental motor areas (SMA). TSSP ratings were significantly correlated with brain activation in somatosensory areas (THAL, S1, left S2), anterior INS, and ACC. These results show that neural responses related to TSSP are evoked in somatosensory processing areas (THAL, S2), as well as in multiple areas that serve other functions related to pain, such as cognition (ACC, PFC), affect (INS, ACC, PAG), pre-motor activity (SMA, cerebellum), and pain modulation (rostral ACC).
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advanced continuous contact heat pulse design for efficient Temporal Summation of second pain windup
The Journal of Pain, 2006Co-Authors: Roland Staud, Donald D Price, Roger B FillingimAbstract:Abstract Temporal Summation of second pain or windup (WU SP ) can be reliably evoked in normal human subjects by repetitive heat pulses to the skin at frequencies of 0.33 Hz or more. This phenomenon is dependent on activation of peripheral C-nociceptors and central N-methyl-D-aspartate receptors, resulting in windup of C-fiber–evoked discharges of dorsal horn neurons. Several investigations of heat pain Summation have used Peltier devices for intermittent-contact heat pulses to the skin. This method returns the skin to an adapting temperature between each stimulus and can result in distinct first and second pain sensations. An alternative method of Temporal Summation consists of continuous-contact heat stimuli by computerized Peltier thermodes that can provide rapid heat pulses. Previously used continuous-contact heat pulse trains, however, seemed to lack characteristics that result in efficient WU SP . The present study sought to obtain psychophysical evidence that reliable WU SP can be elicited with an advanced pulse design by using a computerized heat-foil/Peltier thermode. WU SP was elicited by repetitive thermal stimulation of the hands at frequencies of 0.33 Hz but not 0.25 and 0.17 Hz. WU SP stimuli were either adjusted to resemble the heat transfer characteristics of intermittent-contact stimulus trains, or they remained unadjusted. The estimated transmission velocity of impulses giving rise to second pain and WU SP was characteristic of C fibers. More pronounced second pain and efficient WU SP could be elicited with adjusted than with unadjusted heat pulse trains. Thus, specifically designed continuous-contact heat pulses can be used to elicit distinct second pain and robust WU SP , thereby providing an efficient psychophysical test of this phenomenon. Perspective Temporal Summation testing is rapidly becoming a relevant psychophysical tool for the study of chronic pain disorders. The results of this study will allow more efficient use of currently available constant-contact thermodes for clinical and research applications.
Michael E Robinson - One of the best experts on this subject based on the ideXlab platform.
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usefulness of ramp hold procedures for testing of pain facilitation in human participants comparisons with Temporal Summation of second pain
The Journal of Pain, 2020Co-Authors: Roland Staud, Joseph L Riley, Melyssa M Godfrey, Marlin S Mejia, Riddhi Ramanlal, Michael E RobinsonAbstract:Abstract Quantitative sensory testing (QST) is used to systematically interrogate normal responding and alterations of nervous system function, including pain-related central sensitization (CS). However, up to now, QST of CS in human subjects has been mostly focused on Temporal Summation of second pain (TSSP), has been difficult to perform, and has been associated with low reliability. In contrast, slow ramp & hold (RH) procedures are simpler tests of Temporal Summation and easier to perform. We examined the usefulness of RH procedures as reliable generators of CS using 2 validated QST procedures: decay of pain aftersensations and wind-down. Twenty-seven pain-free subjects (74% female) were enrolled into the study. Trains of sensitivity-adjusted TSSP or RH heat stimuli were applied to the hands of participants to achieve moderate Temporal pain Summation (50 Numerical Rating Scale [NRS] [0–100]). Fifteen-second aftersensations and 30-second wind-down related to TSSP or RH were used for CS comparisons. Reliability of all test procedures was tested over 24 hours. Use of sensitivity-adjusted TSSP and RH heat stimuli resulted in average pain ratings of 48.2 and 49.6 NRS, respectively. Aftersensations or wind-down decay were not significantly different after either TSSP or RH, (all P > .05), indicating that each procedure achieved similar levels of short-term CS. Sensitivity-adjusted RH stimuli were well tolerated and resulted in reliable pain increases of ∼50 NRS. The magnitude of short-term CS, determined by aftersensations and wind-down was similar after sensitivity-adjusted TSSP and RH stimuli (P > .05), suggesting that pain facilitation of healthy participants and likely chronic pain patients can not only be tested with TSSP but also with RH procedures. Perspective This article examines the ability of RH procedures to generate similar central sensitivity augmentation than TSSP. The results suggest that RH is similarly well suited as TSSP to explore central pain mechanisms in healthy subjects and most likely also in chronic pain patients.
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Temporal Summation of second pain variability in responses to a fixed protocol
European Journal of Pain, 2013Co-Authors: Ryan J Anderson, Roland Staud, Joel E Bialosky, Mark D Bishop, Steven Z George, Jason G Craggs, Michael E RobinsonAbstract:Background: Temporal Summation of second pain (TSSP) is relevant for the study of central sensitization, and refers to increased pain evoked by repetitive stimuli at a constant intensity. While the literature reports on participants whose pain ratings increase with successive stimuli, response to a TSSP protocol can be variable. The aim of this study was to characterize the full range of responses to a TSSP protocol in pain-free adults. Method: Three hundred twelve adults received a train of brief, repetitive heat stimuli at a fixed temperature and rated the intensity of second pain after each pulse. TSSP response (D in pain ratings) was quantified using the most common methods in the literature, and response groups were formed: TSSP (D > 0), no change ( D= 0), and Temporal decrease in second pain (TDSP) (D < 0). A cluster analysis was performed on the D values to empirically derive response groups. Results: Depending on how TSSP response was quantified, 61‐72% of the sample demonstrated TSSP, 11‐28% had no change in pain ratings and 0‐20% demonstrated TDSP. The cluster analysis found that the majority (59%) of participants fell in the no change cluster, 29% clustered into the TSSP group and 12% in the TDSP cluster. Conclusions: Using a fixed thermal paradigm, pain-free adults exhibit substantial variability in response to a TSSP protocol not well characterized by group-mean slopes. Studies are needed to determine TSSP response patterns in clinical samples, identify predictors of response and determine the clinical implications of response variability.
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supra threshold scaling Temporal Summation and after sensation relationships to each other and anxiety fear
Journal of Pain Research, 2010Co-Authors: Michael E Robinson, Donald D Price, Joel E Bialosky, Mark D Bishop, Steven Z GeorgeAbstract:This study investigated the relationship of thermal pain testing from three types of quantitative sensory testing (ie, supra-threshold stimulus response scaling, Temporal Summation, and after-sensation) at three anatomical sites (ie, upper extremity, lower extremity, and trunk). Pain ratings from these procedures were also compared with common psychological measures previously shown to be related to experimental pain responses and consistent with fear-avoidance models of pain. Results indicated that supra-threshold stimulus response scaling, Temporal Summation, and after-sensation, were significantly related to each other. The site of stimulation was also an important factor, with the trunk site showing the highest sensitivity in all three quantitative sensory testing procedures. Supra-threshold response measures were highly related to measures of fear of pain and anxiety sensitivity for all stimulation sites. For Temporal Summation and after-sensation, only the trunk site was significantly related to anxiety sensitivity, and fear of pain, respectively. Results suggest the importance of considering site of stimulation when designing and comparing studies. Furthermore, psychological influence on quantitative sensory testing is also of importance when designing and comparing studies. Although there was some variation by site of stimulation, fear of pain and anxiety sensitivity had consistent influences on pain ratings.
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cutaneous c fiber pain abnormalities of fibromyalgia patients are specifically related to Temporal Summation
Pain, 2008Co-Authors: Roland Staud, Michael E Robinson, Courtney E Bovee, Donald D PriceAbstract:Abstract Temporal Summation of “second pain” (TSSP) is considered to be the result of C-fiber-evoked responses of dorsal horn neurons, termed ‘windup’. TSSP is dependent on stimulus frequency (⩾0.33 Hz) and is relevant for central sensitization and chronic pain. We have previously shown that compared to normal controls (NC), fibromyalgia (FM) subjects show abnormal TSSP, requiring lower stimulus intensities/frequencies to achieve similar TSSP. However, it is unknown whether abnormal TSSP in FM is influenced by peripheral sensitization of C-fiber nociceptors and/or bias in pain ratings. Thus, we evaluated 14 FM subjects and 19 NC with pain threshold tests to selective C-fiber stimulation, 30 s heat stimuli, and repetitive brief (1.5 s) heat pulses at 0.33 Hz using a contact heat stimulator (CHEPS). The intensity of heat pulses was varied to achieve maximal TSSP ratings of 45 ± 10 (numerical pain scale 0–100) in both FM and NC groups. We found that NC and FM subjects had similar pain thresholds to C-fiber stimulation and yet FM subjects required lower heat pulse temperatures to generate the same magnitudes of TSSP (p
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brain activity related to Temporal Summation of c fiber evoked pain
Pain, 2007Co-Authors: Roland Staud, Michael E Robinson, Jason G Craggs, William M Perlstein, Donald D PriceAbstract:Temporal Summation of "second pain" (TSSP) is considered to be the result of C-fiber-evoked responses of dorsal horn neurons, termed 'windup'. This phenomenon is dependent on stimulus frequency (0.33 Hz) and relevant for central sensitization and chronic pain. Previous brain imaging studies have only been used to characterize neural correlates of second pain but not its Temporal Summation. We utilized functional magnetic resonance imaging (fMRI) in healthy volunteers to measure brain responses associated with TSSP. Region of interest analysis was used to assess TSSP related brain activation. Eleven pain-free normal subjects underwent fMRI scanning during repetitive heat pulses to the right foot at 0.33 and 0.17 Hz. Stimulus intensities were adjusted to each individual's heat sensitivity to achieve comparable TSSP ratings of moderate pain in all subjects. As predicted, experimental pain ratings showed robust TSSP during 0.33 Hz but not 0.17 Hz stimuli. fMRI statistical maps identified several brain regions with stimulus and frequency dependent activation consistent with TSSP, including contralateral thalamus (THAL), S1, bilateral S2, anterior and posterior insula (INS), mid-anterior cingulate cortex (ACC), and supplemental motor areas (SMA). TSSP ratings were significantly correlated with brain activation in somatosensory areas (THAL, S1, left S2), anterior INS, and ACC. These results show that neural responses related to TSSP are evoked in somatosensory processing areas (THAL, S2), as well as in multiple areas that serve other functions related to pain, such as cognition (ACC, PFC), affect (INS, ACC, PAG), pre-motor activity (SMA, cerebellum), and pain modulation (rostral ACC).
Roger B Fillingim - One of the best experts on this subject based on the ideXlab platform.
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effects of manipulating the interstimulus interval on heat evoked Temporal Summation of second pain across the age span
Pain, 2019Co-Authors: Joseph L Riley, Yenisel Cruzalmeida, Roland Staud, Roger B FillingimAbstract:This study examined the effects of interstimulus interval (ISI) on heat-evoked Temporal Summation of second pain (TSSP) and tested whether greatest maintenance of TSSP would occur at longer ISIs in older adults. Several lines of evidence support that TSSP is associated with central sensitization and is centrally mediated. The participants were 198 community-dwelling adults divided into 3 age cohorts (18-39, 40-59, and 60-78 years of age). Six TSSP trials used a train of 10 contacts with a preheated probe that made repetitive contact with the volar forearm. Participants completed 2 trials at each ISI of 2.5, 3.5, and 4.5 seconds. The intraclass correlations for each pair of trials support the reliability of the current methodology. Temporal Summation of second pain scores declined in a time-dependent manner across ISI. In addition, greater maintenance of TSSP at longer ISIs was observed in middle-aged and older age groups compared with the younger cohort. Significant associations were found between TSSP and measures of recent pain. Greater Summation at longer ISIs in older adults would suggest slower decay of excitability in spinal neurons and infer increased risk for central sensitization with advancing age.
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methodological considerations for the Temporal Summation of second pain
The Journal of Pain, 2017Co-Authors: Nathanial R Eckert, Charles J Vierck, Roger B Fillingim, Roland Staud, Corey B Simon, Sachell Calderon, Yenisel Cruzalmeida, Joseph L RileyAbstract:Abstract Temporal Summation of second pain (TSSP) is a psychophysical indication of a central pain encoding mechanism, potentially enhanced in pathological pain conditions. Low-frequency repetitive stimulation of unmyelinated (C) nociceptors results in a progressive increase of pain intensity when thermal stimulation intensity remains constant. However, when using different methods of nociceptive delivery to the skin, regularity as well as rate of pain enhancement with repetition varies between experiments. Specifically, repetitive ramping up and down from a neutral to a painful temperature has produced weak and inconsistent pain Summation. In contrast, repetitive contact of the skin with a preheated probe has generated substantial pain Summation. In the present study, TSSP by the intermittent contact with a preheated thermode and constant contact, ramp and hold methods were compared during 10 iterations of stimulation of glabrous skin of the hand or hairy forearm skin, with an onset to onset interval of 3.3 seconds and stimulus interval of .8 seconds. Significantly greater TSSP was observed for intermittent contact stimulation at both sites (P Perspective This article presents direct evidence suggesting the constant contact, ramp and hold stimulus may underestimate the level of TSSP. This evidence suggests the re-evaluation of stimulation techniques used for Temporal Summation tests, especially within clinical models.
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novel method for assessing age related differences in the Temporal Summation of pain
PMC, 2016Co-Authors: Kelly M Naugle, Roger B Fillingim, Roland Staud, Yenisel Cruzalmeida, Joseph L RileyAbstract:Temporal Summation (TS) of pain protocols typically involve the delivery of brief repetitive noxious stimuli held at a constant intensity and measuring the consequent increase in the perceived intensity of pain sensations. To date, no studies have examined the effect of a TS protocol on the perceived spatial dimensions of the pain experience and its interaction with age. This study used a new TS protocol that examined changes in the perceived size of the painful area in 22 younger adults and 20 older adults. Four trials of ten brief heat pulses delivered at a constant intensity were administered on the volar forearm. Interpulse intervals (IPIs) were 2.5 seconds or 3.5 seconds. Subjects rated the peak pain intensity (trials 1 and 3) or the size of the painful area (trials 2 and 4) after each pulse on a 0–100 scale. The magnitude of Summation was calculated for each trial. Three seconds and 6 seconds after delivering the last heat pulse, the subjects rated the intensity or the size of any remaining pain (aftersensations). The results indicated that older adults compared to younger adults exhibited significantly greater Summation of size ratings for the 2.5-second and 3.5-second IPI trials and size of pain aftersensations at 3 seconds following the 2.5-second IPI TS trial. These results suggest that aging is associated with enhanced endogenous facilitation of the perceived size of pain. The potential clinical and mechanistic implications of enhanced TS of size of pain remain unknown and warrant further investigation.
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advanced continuous contact heat pulse design for efficient Temporal Summation of second pain windup
The Journal of Pain, 2006Co-Authors: Roland Staud, Donald D Price, Roger B FillingimAbstract:Abstract Temporal Summation of second pain or windup (WU SP ) can be reliably evoked in normal human subjects by repetitive heat pulses to the skin at frequencies of 0.33 Hz or more. This phenomenon is dependent on activation of peripheral C-nociceptors and central N-methyl-D-aspartate receptors, resulting in windup of C-fiber–evoked discharges of dorsal horn neurons. Several investigations of heat pain Summation have used Peltier devices for intermittent-contact heat pulses to the skin. This method returns the skin to an adapting temperature between each stimulus and can result in distinct first and second pain sensations. An alternative method of Temporal Summation consists of continuous-contact heat stimuli by computerized Peltier thermodes that can provide rapid heat pulses. Previously used continuous-contact heat pulse trains, however, seemed to lack characteristics that result in efficient WU SP . The present study sought to obtain psychophysical evidence that reliable WU SP can be elicited with an advanced pulse design by using a computerized heat-foil/Peltier thermode. WU SP was elicited by repetitive thermal stimulation of the hands at frequencies of 0.33 Hz but not 0.25 and 0.17 Hz. WU SP stimuli were either adjusted to resemble the heat transfer characteristics of intermittent-contact stimulus trains, or they remained unadjusted. The estimated transmission velocity of impulses giving rise to second pain and WU SP was characteristic of C fibers. More pronounced second pain and efficient WU SP could be elicited with adjusted than with unadjusted heat pulse trains. Thus, specifically designed continuous-contact heat pulses can be used to elicit distinct second pain and robust WU SP , thereby providing an efficient psychophysical test of this phenomenon. Perspective Temporal Summation testing is rapidly becoming a relevant psychophysical tool for the study of chronic pain disorders. The results of this study will allow more efficient use of currently available constant-contact thermodes for clinical and research applications.
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fear avoidance beliefs and Temporal Summation of evoked thermal pain influence self report of disability in patients with chronic low back pain
Journal of Occupational Rehabilitation, 2006Co-Authors: Steven Z George, Roger B Fillingim, Virgil T Wittmer, Michael E RobinsonAbstract:Introduction: Quantitative sensory testing has demonstrated a promising link between experimentally determined pain sensitivity and clinical pain. However, previous studies of quantitative sensory testing have not routinely considered the important influence of psychological factors on clinical pain. This study investigated whether measures of thermal pain sensitivity (Temporal Summation, first pulse response, and tolerance) contributed to clinical pain reports for patients with chronic low back pain, after controlling for depression or fear-avoidance beliefs about work. Method: Consecutive patients (n=27) with chronic low back pain were recruited from an interdisciplinary pain rehabilitation program in Jacksonville, FL. Patients completed validated self-report questionnaires for depression, fear-avoidance beliefs, clinical pain intensity, and clinical pain related disability. Patients also underwent quantitative sensory testing from previously described protocols to determine thermal pain sensitivity (Temporal Summation, first pulse response, and tolerance). Hierarchical regression models investigated the contribution of depression and thermal pain sensitivity to clinical pain intensity, and fear-avoidance beliefs and thermal pain sensitivity to clinical pain related disability. Results: None of the measures of thermal pain sensitivity contributed to clinical pain intensity after controlling for depression. Temporal Summation of evoked thermal pain significantly contributed to clinical pain disability after controlling for fear-avoidance beliefs about work. Conclusion: Measures of thermal pain sensitivity did not contribute to pain intensity, after controlling for depression. Fear-avoidance beliefs about work and Temporal Summation of evoked thermal pain significantly influenced pain related disability. These factors should be considered as potential outcome predictors for patients with work-related low back pain. Signifance: This study supported the neuromatrix theory of pain for patients with CLBP, as cognitive-evaluative factor contributed to pain perception, and cognitive-evaluative and sensory-discriminative factors uniquely contributed to an action program in response to chronic pain. Future research will determine if a predictive model consisting of fear-avoidance beliefs and Temporal Summation of evoked thermal pain has predictive validity for determining clinical outcome in rehabilitation or vocational settings.
