Temporal Summation Of Second Pain Research Articles

Spatial factors influencing the pain-ameliorating effect of CT-optimal touch: a comparative study for modulating temporal summation of second pain

Recent studies show that CT-optimal touch, gentle slow stroking of the skin, can reduce pain. However, much is unknown regarding the factors influencing its pain-ameliorating effect, such as tactile attention and touch application site. The current study investigates in 36 healthy individuals, whether CT-optimal touch can reduce temporal summation of second pain (TSSP) compared to CT non-optimal touch and tapping the skin. TSSP refers to activation of the C-nociceptors; by stimulating these fibers a burning and/or tingling sensation can be elicited. All participants underwent three conditions on both the contralateral and ipsilateral side of pain induction. The results show that tapping the skin did not reduce TSSP, meaning that pain reduction through touch cannot be explained by tactile attention effects. CT non-optimal touch only reduced TSSP when applied on the ipsilateral side. Importantly, CT-optimal touch effectively reduced TSSP when applied on the contralateral or ipsilateral side. Furthermore, CT-optimal touch was more effective in reducing TSSP compared to CT non-optimal touch and Tapping. This study shows that that CT-optimal touch can reduce TSSP and this effect appears to be independent of touch application site, which is highly relevant for implementing CT-optimal touch as a treatment.

Examination of Conditioned Pain Modulation in Myofascial TMD With Consideration of Temporal Summation

Research on myofascial temporomandibular disorder (mTMD) has often focused on potential dysfunction in endogenous pain modulation. However, studies on the specific inhibitory and facilitatory components of endogenous pain modulation using conditioned pain modulation (CPM) and temporal summation of second pain (TSSP) have shown mixed results. This study aimed to 1) examine whether women with mTMD demonstrated efficient CPM compared to controls; 2) explore the association between independent measures of CPM and TSSP in women with mTMD relative to controls; and 3) determine whether resulting modulatory profiles differentially predicted pain intensity among cases. All participants were recruited from dental clinics. Cases were women who met the research diagnostic criteria for mTMD. Controls did not have facial pain on exam and were selected to be sociodemographically similar to cases. CPM and TSSP were assessed via independent psychophysical protocols. CPM was examined in linear mixed models predicting pain thresholds adjusted for age and stratified by TSSP. Mean CPM was estimated at a 2.2 (SD = 2.8) degree increase in pain thresholds (P ≤ .001), similar in cases and controls (P = .67). CPM was less efficient in cases with enhanced TSSP (P = .031), but not in controls. Although the double-pronociceptive profile of both low CPM and high TSSP trended higher among cases than controls, it did not predict higher levels of pain intensity among cases. This study does not support deficient inhibitory endogenous pain modulation in mTMD, but results suggest that inhibitory and facilitatory pain modulation should be examined concomitantly in the study of endogenous pain modulation. PerspectiveThis manuscript presents a novel examination of inhibitory modulation by the level of facilitatory modulation in mTMD. The findings and approach may prove useful for mechanistic researchers studying endogenous pain modulation and clinical researchers seeking to jointly examine conditioned pain modulation and temporal summation in future research on chronic pain.

Clinical identification of the stimulus intensity to measure temporal summation of second pain

Temporal summation of second pain (TSSP) has been suggested as a psychophysical index for central sensitization, one of the critical mechanisms in the chronification of pain. However, there is no gold standard for protocols to measure TSSP. The purpose was to establish the stimulus intensity for measuring TSSP. Female patients with chronic myofascial temporomandibular disorders pain (n = 16) and healthy female volunteers with no pain (n = 15) participated. Pain thresholds (PT °C) were measured, and repetitive heat stimuli at three stimulus intensities (PT °C, PT + 1 °C, PT + 2 °C) were applied. TSSP parameters were quantified as TSSP magnitude (TSm) and TSSP frequency (TSf). In healthy female volunteers, pain ratings significantly decreased at PT °C (p < 0.050), besides TSm and TSf at PT + 2 °C were significantly higher than those at PT °C (p < 0.025). In chronic pain patients, pain ratings significantly increased at PT + 1 °C and PT + 2 °C (p < 0.050). At PT + 2 °C, TSm and TSf in chronic pain patients were significantly higher than those in healthy volunteers (p < 0.050). It could be helpful to measure TSSP with the stimulus intensity adjusted individually to the patient’s pain thresholds + 2 °C for assessing central sensitization.

Spinal cord neural activity of patients with fibromyalgia and healthy controls during temporal summation of pain: an fMRI study.

The cause for the increased sensitivity of patients with fibromyalgia (FM) to painful stimuli is unclear but sensitization of dorsal horn spinal cord neurons has been suggested. There, critical changes of sensory information occur which depend on the plasticity of second-order neurons and descending pain modulation, including facilitation and inhibition. This study used repetitive stimuli that produce temporal-summation-of-second-pain (TSSP) and central sensitization, relevant mechanisms for patients with chronic pain. We examined spinal cord neural activation during TSSP in patients with FM and healthy controls (HC) and used its functional connectivity with several brainstem nuclei to model the observed blood-oxygen-level-dependent (BOLD) time-course with pain ratings. Sixteen HC and 14 FM participants received repetitive heat stimuli to the hand at 0.4 Hz to achieve TSSP during functional imaging with a 3 T-Philips Achieva MRI scanner. Stimuli were adjusted to each individual's pain sensitivity to achieve maximal pain ratings of 50 ± 10 on a numerical pain scale (0-100). Using a 16-channel neurovascular coil, multiple image series were obtained from the cervical spinal cord to the brainstem using single-shot turbo-spin echo sequences. During repetitive, sensitivity-adjusted heat stimuli, pain ratings of all subjects increased as predicted, consistent with TSSP. HC and FM participants had similar temporal patterns of spinal activation: initial BOLD increase followed by deactivation. Structural equation modeling showed that the observed spinal activity during TSSP was associated with more BOLD activity across/within the brainstem in FM subjects than HC, suggesting differences in pain modulation.NEW & NOTEWORTHY "Windup" and its behavioral correlate "temporal-summation-of-second pain" (TSSP) represent spinal cord mechanisms of pain augmentation associated with central sensitization and chronic pain. Fibromyalgia (FM) is a chronic pain disorder, where abnormal TSSP has been demonstrated. We used fMRI to study spinal cord and brainstem activation during TSSP. We characterized the time course of spinal cord and brainstem BOLD activity during TSSP which showed abnormal brainstem activity in patients with FM, possibly due to deficient pain modulation.

Does Quantitative Sensory Testing Improve Prediction of Chronic Pain Trajectories? A Longitudinal Study of Youth With Functional Abdominal Pain Participating in a Randomized Controlled Trial of Cognitive Behavioral Treatment.

Youth with functional abdominal pain (FAP) experience significant pain-related distress and functional impairment. Although quantitative sensory testing protocols have identified alterations in pain modulatory systems that distinguish youth with FAP from healthy controls, the extent to which evoked pain responses predict subsequent trajectories of pain symptoms and disability over and above established psychosocial risk factors is unclear. The present study included 183 adolescents with FAP who were enrolled in a randomized controlled trial comparing an 8-week, internet-delivered program of cognitive behavior therapy (n=90) or pain education (n=93). Participants completed a quantitative sensory testing protocol before the intervention and were followed for 12-month posttreatment. Whereas adolescents with FAP who exhibited stronger baseline conditioned pain modulation (CPM) reported decreases in pain-related interference over follow-up (b=-0.858, SE=0.396, P=0.032), those with weaker CPM exhibited high, relatively stable levels of pain-related interference over time (b=-0.642, SE=0.400, P=0.110). CPM status predicted changes in pain-related interference after controlling for the effects of treatment condition and psychosocial risk factors. Static measures of pain sensitivity (ie, pain threshold, pain tolerance) and temporal summation of second pain were not associated with changes in measures of abdominal pain, gastrointestinal symptom severity, or pain-related interference over follow-up. The present findings contribute to a growing literature on the predictive utility of quantitative sensory testing indices and suggest that CPM may complement existing psychosocial risk measures in determining individualized pain-related risk profiles.

Impact of Music on First Pain and Temporal Summation of Second Pain

Passive music listening has shown its capacity to soothe pain in several clinical and experimental studies. This phenomenon—known as music-induced 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 &amp;lt; .02). Repeated measures ANOVA indicated significant differences between conditions within PP and TS (p &amp;lt; .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.

A Better Touch: C-tactile Fibers Related Activity is Associated to Pain Reduction During Temporal Summation of Second Pain

C-tactile (CT) fibers, responsible for the so-called “affective” touch (AT), have drawn a fair amount of attention within the scientific community for their marked social dimension. However, while the pain-relieving potential of discriminative touch (DT) has been documented, proofs of the analgesic properties of AT are still scarce. Additionally, no study has so far tested its possible pain-relieving effects on a clinically-relevant model. Temporal summation of second pain (TSSP), otherwise referred to as “wind-up,” relies on repetitive stimulation of C-nociceptors and it is thought to reflect central sensitization, a process linked to many chronic pain conditions. In the present experimental, within participants, design we induced TSSP through trains of ascending and descending repetitive heat stimulation. Forty-two healthy participants’ pain was measured during 2 different tactile stimulations (stroking velocities AT: 10 cm/s; DT: 0.3 cm/s) or without concomitant tactile input. Since measures of pleasantness of the tactile stimulation have been found to strongly correlate with C-tactile fibers’ firing rate, these, together with participants’ body awareness, were also taken into account.Our results show that AT brought about a decrease of our participants’ pain as opposed to both DT and no touch, while DT did not produce any significant pain reduction. Thus, only AT successfully modulated wind-up. As expected, AT was perceived as more pleasant than DT, while a clear relationship between body awareness and pain was found only during DT.Targeting CT fibers could pave the way to new treatments for chronic pain conditions whose aetiology depend on abnormal C-nociceptors’ physiology. PerspectiveThis study extends previous findings on the analgesic potential of affective touch, documenting a clear pain reduction during temporal summation of second pain (TSSP). Since TSSP is thought to reflect central sensitization, the psychophysiological mechanisms of affective touch could be exploited for new chronic pain treatments.

Usefulness of Ramp & Hold Procedures for Testing of Pain Facilitation in Human Participants: Comparisons With Temporal Summation of Second Pain

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. PerspectiveThis 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.

Childhood Adversity and Pain Facilitation.

This study investigated whether childhood adversity would be associated with hypersensitivity on two measures of central pain facilitation: area of secondary allodynia and temporal summation of second pain (TSSP), and whether pain facilitation would be explained by adult posttraumatic stress disorder (PTSD) symptoms. Participants endorsing high (n = 31) and low (n = 31) childhood adversity underwent capsaicin-induced secondary allodynia and TSSP testing. The tests were conducted a week apart with test order counterbalanced. Larger areas of secondary allodynia were observed in the high adversity group compared with the low adversity group (F(1,60) = 4.81, p = .032). This group difference was largely (62%) explained by greater PTSD symptoms in the high adversity group. Although no overall difference was found in TSSP slopes (p = .886), this was attributed to an order by group interaction (F(1,58) = 5.07, p = .028) and low power. Subsequent analyses revealed positive TSSP slopes in the high adversity group when TSSP testing was performed first, and this order effect was associated with blunted sympathetic responses to TSSP on the first visit. The two facilitation measures were unrelated (p = .631). Larger areas of secondary allodynia were observed in the high adversity group, which was explained largely by PTSD symptoms. This suggests that adversity-related changes in pain facilitation may underlie the association between childhood adversity and generalized widespread pain. Although TSSP was affected by previous testing, adversity-related pain facilitation was observed when TSSP testing occurred first. Finally, adversity was not associated with a consistent pattern of hypersensitivity across the two measures of central pain facilitation.

Effects of manipulating the interstimulus interval on heat-evoked temporal summation of second pain across the age span.

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.

Methodological Considerations for the Temporal Summation of Second Pain.

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.

Association Between Borderline Personality Features and Temporal Summation of Second Pain: A Cross-Sectional Study

ABSTRACTIndividuals with greater borderline personality features may be vulnerable to chronic pain. Because pain is an unpleasant sensory and emotional experience, affect dysregulation as the core personality feature may be linked to pain hypersensitivity. Studies have found that greater borderline features are associated with increased intensity in clinical and experimental pain, and that depression mediates this increase. The current study further examined the association between borderline features and heat pain sensitivity, the contribution of affect dysregulation and the other borderline personality factors (identity problems, negative relationships, self-harming/impulsivity) to the association, and depression as a mediator. Additionally, we examined whether blunted sympathetic responses mediate the association between borderline features and temporal summation of second pain (TSSP). Thermal pain threshold, thermal TSSP and aftersensations pain were assessed in 79 healthy individuals with varying degrees of borderline features. TSSP is a proxy measure for central sensitization and refers to the gradual increase in pain to repeated nociceptive stimuli. A regression analysis showed that greater borderline features predicted greater TSSP (β = .22, p = .050, R2 = .05). Borderline features were unrelated to pain threshold and TSSP decay. A stepwise regression showed greater TSSP in individuals with greater borderline features was accounted for by the negative relationships factor rather than the affect dysregulation factor. The results of mediational analyses showed depression and blunted sympathetic skin conductance responses mediated the positive association between TSSP and borderline features.

(445) Increased Spinal Cord Neuronal Activity of Healthy Individuals Correlates with Temporal Summation of Second Pain

(445) Increased Spinal Cord Neuronal Activity of Healthy Individuals Correlates with Temporal Summation of Second Pain

Childhood Adversity and Pain Sensitization

Childhood adversity is a vulnerability factor for chronic pain. However, the underlying pain mechanisms influenced by childhood adversity remain unknown. The aim of the current study was to evaluate the impact of childhood adversity on dynamic pain sensitivity in young adults. After screening for childhood adverse events and health status, healthy individuals reporting low (below median; n = 75) or high levels of adversity (the top 5%; n = 51) were invited for pain testing. Both groups underwent heat pain threshold and temporal summation of second pain (TSSP) testing after reporting depressive symptoms. TSSP refers to a progressive increase in pain intensity with repetition of identical noxious stimuli and is attributed to central sensitization. Changes in pain ratings over time (slope) were computed for TSSP sensitization and decay of subsequent aftersensations. The high-adversity group showed greater TSSP sensitization (meanslope, 0.75; SDpositive slope, 1.78), and a trend toward a slower decay (meanslope, -11.9; SD, 3.4), whereas the low-adversity group showed minimal sensitization (meanslope, 0.07; SDnear-zero slope, 1.77), F(1,123) = 5.84, p = .017 and faster decay (meanslope, -13.1; SD, 3.4), F(1,123) = 3.79, p = .054. This group difference remained significant even after adjusting for adult depressive symptoms (p = .033). No group difference was found in heat pain threshold (p = .85). Lastly, the high-adversity group showed blunted cardiac and skin conductance responses. These findings suggest that enhancement of central sensitization may provide a mechanism underlying the pain hypersensitivity and chronicity linked to childhood adversity.

FMRI of spinal and supra-spinal correlates of temporal pain summation in fibromyalgia patients.

Fibromyalgia syndrome (FM) is a debilitating chronic pain condition, which afflicts primarily females. Although the etiology of this illness is not completely understood, FM pain is thought to rely on enhanced pain sensitivity maintained by central mechanisms. One of these mechanisms is central pain amplification, which is characterized by altered temporal summation of second pain (TSSP). Here we use a TSSP paradigm and functional MRI (fMRI) of the spinal cord, brainstem, and brain to noninvasively examine the central nervous system contributions to TSSP in FM patients and normal controls (NC). Functional MRI of pain-free female adults (N = 15) and FM patients (N = 14) was conducted while brief, repetitive heat pain stimuli (0.33 Hz) were applied to the thenar eminence of the hand (C6 dermatome). The stimulus intensity was adjusted to each participant's heat pain sensitivity to achieve moderate pain. Data were analyzed by means of a General Linear Model and region-of-interest analyses. All participants demonstrated significant pain summation in the TSSP condition. FM subjects, however, required significantly lower stimulus intensities than NC to achieve similar TSSP. fMRI analyses of perceptually equal TSSP identified similar brain activity in NC and FM subjects; however, multiple areas in the brainstem (rostral ventromedial medulla and periaqueductal grey region) and spinal cord (dorsal horn) exhibited greater activity in NC subjects. Finally, increased after-sensations and enhanced dorsal horn activity was demonstrated in FM patients. In conclusion, the spinal and brainstem BOLD responses to TSSP are different between NC and FM patients, which may indicate alterations to descending pain control mechanisms suggesting contributions of these mechanisms to central sensitization and pain of FM patients.

Neural correlates of temporal summation of second pain in the human brainstem and spinal cord.

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.

Race effects on temporal summation to heat pain in youth.

Racial differences in pain responsiveness have been demonstrated in adults. However, it is unclear whether racial differences are also present in youth and whether they extend to experimental pain indices assessing temporal summation of second pain (TSSP). Temporal summation of second pain provides an index of pain sensitivity and may be especially relevant in determining risk for chronic pain. This study assessed pain tolerance and TSSP to evoked thermal pain in 78 healthy youth (age range, 10-17), 51% of whom were African American and 49% were non-Hispanic white. Multilevel models revealed within-individual increases in pain ratings during the temporal summation task in non-Hispanic white youth that were consistent with TSSP. Pain ratings did not change significantly during the temporal summation task in African-American youth. Baseline evoked pain ratings were significantly higher in African-American compared with non-Hispanic white youth. These findings suggest that enhanced responsiveness to evoked thermal pain in African Americans is present in adolescence but is unlikely to be related to elevated TSSP. These results may have implications for understanding racial differences in chronic pain experience in adulthood.

(306) Shoulder pathology and surgical procedure are not predictive of post-surgical temporal summation of second pain

(306) Shoulder pathology and surgical procedure are not predictive of post-surgical temporal summation of second pain

Depression as a mediator of the relationship between temporal summation of second pain and subclinical borderline personality characteristics

Borderline personality (BP) is characterized by affect dysregulation and is positively associated with chronic pain. Previously, our laboratory observed that affect dysregulation was associated with enhanced temporal summation of second pain (TSSP). TSSP refers to the sensitization of pain evoked by repetitive heat pulses applied to the skin, which reflects a summation process of peripheral C-fiber nociceptive inputs and NMDA mediated sensitization of spinal dorsal horn neurons. However, further study is needed to investigate psychological mediators of enhanced pain sensitivity in individuals with BP characteristics. The purpose of this study is to examine whether depression mediates the relationship between affect dysregulation and central sensitization. TSSP was induced by 10 heat pulses in three trials. Before TSSP testing, sensitivity tests were conducted to identify a peak temperature to induce moderate pain (35 to 55 out of a 0-100 scale). While a thermode was applied to the thenar eminence of the non-dominant hand, participants rated their subjective pain after each peak. BP characteristics were assessed by the Personality Assessment Inventory-Borderline scale (PAI-BOR) and depression was assessed by the Center for Epidemiologic Studies Depression Scale in 80 pain-free college students. TSSP was compared between the two groups with the low (< 50) and high (>50 and <70) PAI-BOR T scores using a repeated measures ANOVA (10 ratings of average pain at each pulse in the three trials by 2 groups). The results indicated a significant interaction between group and repeated pulses after controlling for peak temperatures (F (9, 223) = 4.24, p = .01, epsilon=.25). The high PAI-BOR group reported significantly higher pain in the later pulse train. Analysis of covariance indicated that the interaction is no longer significant after controlling for depressive symptoms (p > .05). These findings suggest that the relationship between affect dysregulation and enhanced central sensitization is mediated by depressive symptoms.

A closer look at temporal summation of second pain in healthy persons

A closer look at temporal summation of second pain in healthy persons