A myriad of methods to determine temporal summation of pain in people with musculoskeletal pain and healthy participants: a scoping review.

Temporal summation of pain (TSP) is a human proxy for wind-up of dorsal horn neurons as assessed in animals. The common paradigm for eliciting TSP is evoked by repetitive nociceptive stimuli of equal intensity. Various stimulation and assessment protocols have been used. This scoping review aims to provide insight into key elements of TSP stimulation and assessment: modality, instruments, test location, familiarization, train characteristics, and calculations. PubMed, Embase, and Ebsco/CINAHL were searched for studies that measured TSP in adults with musculoskeletal conditions and healthy people. Four hundred six studies were included. Mechanical stimuli were the most commonly used modality (250 studies), followed by thermal stimuli (125 studies). Forty-six different instruments were used. Disregarding studies on widespread musculoskeletal pain and healthy participants, 40 studies evaluated TSP at painful sites, 77 in remote areas, and 66 in both locations. Of the 13 tested locations in patients, the hand (74 studies), lower leg (64 studies), and forearm (59 studies) were most commonly tested. A single practice round was the most common familiarization method (46 studies). Repeated stimuli were applied using 31 different frequencies (0.03-200 Hz) and sustained stimulations ranging from 5 to 1080 seconds were used. Twenty-two different train lengths, 63 different calculations (37 absolute, 19 relative, and 7 alternatives using data directly), and 14 different outcome measures (eg, self-reported pain rating scales and reflex thresholds) were used. Temporal summation of pain protocols vary excessively, hindering the comparison and pooling of results. None of the studies provided substantiation for their protocol choice.

Temporal Summation but Not Expectations of Pain Relief Predict Response to Acupuncture Treatment in Fibromyalgia.

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

Association between central sensitivity syndrome and psychophysical factors in patients with masticatory myofascial pain.

PURPOSE: This study explored the relationship between central sensitization symptoms, assessed using the Central Sensitization Inventory (CSI), and psychophysical factors in patients with chronic masticatory myofascial pain (MMP) transitioning from the acute to chronic stages. METHODS: In this study, 23 patients with MMP and 22 healthy volunteers were assessed using psychophysical tests, including measurements of pressure pain threshold (PPT) and temporal summation of pain (TSP). Additionally, CSI scores were recorded to evaluate central sensitization symptoms. RESULTS: Patients with chronic MMP showed significantly lower PPT in all masticatory muscles and extratrigeminal areas compared with controls. However, there was no significant correlation between CSI scores and psychophysical test results in patients with MMP. CONCLUSION: The significant enhancement of TSP in patients with subchronic MMP suggests a potential role in the onset of myofascial pain. The main finding suggests that sub-chronic symptom patients show higher CSI scores despite no sensory testing changes, indicating that central sensitization possibly precedes observable symptoms.

Chronic sleep deficiency and its impact on pain perception in healthy females.

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.

Temporal summation of second pain is affected by cognitive load.

This work attempted to clarify the interaction of cognition and pain sensitization during a paradigm of Temporal Summation of Second Pain (TSSP). We analyzed pain ratings and electroencephalographic (EEG) activity obtained from 21 healthy participants during the presentation of four experimental conditions that differed in the manipulation of attention to painful stimuli or working memory load (Attention to hand & TSSP; 0-back & TSSP (low cognitive load); 2-back & TSSP (high cognitive load); 2-back (without pain)). We found that the TSSP was reduced when the attention was diverted and the cognitive load increased, and this reduction was accompanied by higher midfrontal theta activity and lower posterior alpha and central beta activity. Although it is well established that TSSP is a phenomenon that occurs at the spinal level, here we show that it is also affected by supraspinal attentional mechanisms. Delivery of painful repeated stimuli did not affect the performance of the 2-back task but was associated with smaller amplitudes of attentional event-related potentials (ERPs) after standard stimuli (not the target). The study of brain activity during TSSP allowed to clarify the role of top-down attentional modulation in pain sensitization processes. Results contribute to a better understanding of cognitive dysfunction in pain conditions and reinforce the use of therapeutic strategies based on distracting attention away from pain.

Temporal resolution relates to sensory hyperreactivity independently of stimulus detection sensitivity in individuals with autism spectrum disorder.

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

Effects of motor imagery using virtual reality on pain sensitivity and affect in healthy individuals: A prospective randomized crossover study.

OBJECTIVE: Exercise induces a hypoalgesic response and improves affect. However, some individuals are unable to exercise for various reasons. Motor imagery, involving kinesthetic and visual imagery without physical movement, activates brain regions associated with these benefits and could be an alternative for those unable to exercise. Virtual reality also enhances motor imagery performance because of its illusion and embodiment. Therefore, we examined the effects of motor imagery combined with virtual reality on pain sensitivity and affect in healthy individuals. DESIGN: Randomized crossover study. SETTING: Laboratory. SUBJECTS: Thirty-six participants (women: 18) were included. METHODS: Each participant completed three 10-min experimental sessions, comprising actual exercise, motor imagery only, and motor imagery combined with virtual reality. Hypoalgesic responses and affective improvement were assessed using the pressure-pain threshold and the Positive and Negative Affect Schedule, respectively. RESULTS: All interventions significantly increased the pressure-pain threshold at the thigh (P<0.001). Motor imagery combined with virtual reality increased the pressure-pain threshold more than motor imagery alone, but the threshold was similar to that of actual exercise (both P≥0.05). All interventions significantly decreased the negative affect of the Positive and Negative Affect Schedule (all P<0.05). CONCLUSIONS: Motor imagery combined with virtual reality exerted hypoalgesic and affective-improvement effects similar to those of actual exercise.

Is the Central Sensitization Inventory (CSI) associated with quantitative sensory testing (QST)? A systematic review and meta-analysis.

Central sensitization (CS) involves an amplification of neural processing within the central nervous system that can result in widespread pain patterns and hypersensitivity to stimuli. The Central Sensitization Inventory (CSI) and various quantitative sensory testing (QST) methods purport to assess clinical markers of CS. The purpose of this systematic review and meta-analysis was to summarize and quantify the associations between total CSI scores and QST measures from previous studies. A systematic search identified 39 unique studies that were deemed eligible for the systematic review and 33 studies for meta-analyses (with 3314 subjects and 154 effect sizes), including five QST modalities: conditioned pain modulation, temporal summation, pressure pain threshold, heat pain threshold, and cold pain threshold. The meta-analysis yielded statistically significant CSI-QST correlations in total subject samples for all five QST modalities. The strongest associations were identified between CSI scores and pain threshold testing, especially pressure pain threshold, in which 51% of effects sizes, from 29 studies and 3071 subjects, were determined to be in a medium to large range.

Pain Science in Practice (Part 7): How Is Descending Modulation of Pain Measured?

SYNOPSIS: Understanding the descending pain modulatory system allows for a neuroscientific explanation of naturally occurring pain relief. Evidence from basic science and clinical studies on the effectiveness of drugs in certain patient groups led to pharmacological manipulation of the descending pain modulatory system for analgesia. Understanding mechanisms and theories helps clinicians make sense of chronic musculoskeletal pain. This editorial explains how test paradigms, including conditioned pain modulation, offset analgesia, and stress-induced analgesia work, provide an overview of a placebo analgesia circuitry, and discusses how evoking activity in the descending pain modulatory system using specific paradigms can give new insights into how specific treatments work to reduce pain. J Orthop Sports Phys Ther 2024;54(2):1-6. doi:10.2519/jospt.2024.12113.

Hyperalgesia, Increased Temporal Summation and Impaired Inhibitory Mechanisms in Episodic and Chronic Cluster Headache: An Observational Study.

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

Optimizing Temporal Summation of Heat Pain Using a Constant Contact Heat Stimulator.

Purpose: Temporal summation (TS) of pain occurs when pain increases over repeated presentations of identical noxious stimuli. TS paradigms can model central sensitization, a state of hyperexcitability in nociceptive pathways that promotes chronic pain onset and maintenance. Many experimenters use painful heat stimuli to measure TS (TS-heat); yet, TS-heat research faces unresolved challenges, including difficulty evoking summation in up to 30-50% of participants. Moreover, substantial variability exists between laboratories regarding the methods for evoking and calculating TS-heat. Patients and Methods: To address these limitations, this study sought to identify optimal parameters for evoking TS-heat in healthy participants with a commercially available constant contact heat stimulator, the Medoc TSA-II. Working within constraints of the TSA-II, stimulus trains with varying parameters (eg, stimulus frequency, baseline temp, peak temp, peak duration, testing site) were tested in a sample of 32 healthy, chronic pain-free participants to determine which combination best evoked TS-heat. To determine whether TS scoring method altered results, TS-heat was scored using three common methods. Results: Across all methods, only two trains successfully evoked group-level TS-heat. These trains shared the following parameters: site (palmar hand), baseline and peak temperatures (44°C and 50°C, respectively), and peak duration (0.5 s). Both produced summation that peaked at moderate pain (~50 out of 100 rating). Conclusion: Future TS-heat investigations using constant contact thermodes and fixed protocols may benefit from adopting stimulus parameters that include testing on the palmar hand, using 44°C baseline and 50°C peak temperatures, at ≥0.33 Hz stimulus frequency, and peak pulse durations of at least 0.5 seconds.

The Impact of Sleep Disturbances on Endogenous Pain Modulation: A Systematic Review and Meta-Analysis.

The bidirectional relationship between sleep and pain problems has been extensively demonstrated but despite all the accumulating evidence, their shared mechanisms are currently not fully understood. This review examined the association between sleep disturbances, defined as a broad array of sleep-related outcomes (eg, poor quality, short duration, insomnia), and endogenous pain modulation (EPM) in healthy and clinical populations. Our search yielded 6,151 references, and 37 studies met the eligibility criteria. Qualitative results showed mixed findings regarding the association between sleep disturbances and temporal summation of pain (TSP) and conditioned pain modulation (CPM), with poor sleep more commonly associated with decreased pain inhibition in both populations. Quantitative results indicated that such associations were not statistically significant, neither in healthy populations when EPM outcomes were assessed for changes pre-/post-sleep intervention (TSP: .31 [95%CI: -.30 to .92]; P = .321; CPM: .40 [95%CI: -.06 to .85] P = .088) nor in clinical populations when such association was assessed via correlation (TSP: -.00 [95%CI: -.22 to .21] P = .970; CPM: .12 [95%CI: -.05 to .29]; P = .181). For studies that reported results by sex, meta-analysis showed that experimental sleep disturbances impaired pain inhibition in females (1.43 [95%CI: .98-1.88]; P < .001) but not in males (-.30 [95%CI: -2.69 to 1.60]; P = .760). Only one study investigating the association between sleep disturbances and offset analgesia was identified, while no studies assessing spatial summation of pain were found. Overall, this review provides a comprehensive overview of the association between sleep disturbances and EPM function, emphasizing the need for further investigation to clarify specific mechanisms and phenotypic subtypes. PERSPECTIVE: This review shines a light on the association between sleep disturbances and endogenous pain modulation function. Qualitatively, we found a frequent association between reduced sleep quality and impaired pain inhibition. However, quantitatively such an association was not corroborated. Sex-specific effects were observed, with females presenting sleep-related impaired pain inhibition but not males.

Conditioned Pain Modulation and Temporal Summation of Pain in Patients With Traumatic and Non-Specific Neck Pain: A Systematic Review and Meta-Analysis.

In patients with neck pain, it is unclear whether pain inhibition and facilitation endogenous pain mechanisms are altered. This systematic review and meta-analysis aimed to improve their understanding by assessing conditioned pain modulation (CPM) and temporal summation of pain (TSP) in patients with neck pain associated with whiplash-associated disorders (WAD) or of a nonspecific neck pain (NSNP) nature compared to pain-free controls. Very low certainty evidence suggests: impaired CPM when assessed remotely in chronic WAD patients (n = 7, 230 patients and 204 controls, standardized mean differences (SMD) = -.47 [-.89 to -.04]; P = .04) but not locally (n = 6, 155 patients and 150 controls; SMD = -.34 [-.68 to .01]; P = .05), impaired CPM in chronic NSNP patients when assessed locally (n = 5, 223 patients and 162 controls; SMD = -.55 [-1.04 to -.06]; P = .04) but not remotely (n = 3, 72 patients and 66 controls; SMD = -.33 [-.92 to .25]; P = .13), TSP not facilitated in either chronic WAD (local TSP: n = 4, 90 patients and 87 controls; SMD = .68 [-.62 to 1.99]) (remote TSP: n = 8, 254 patients and 214 controls; SMD = .18 [-.12 to .48]) or chronic NSNP (local TSP: n = 2, 139 patients and 92 controls; SMD = .21 [-1.00 to 1.41]), (remote TSP: n = 3; 91 patients and 352 controls; SMD = .60 [-1.33 to 2.52]). The evidence is very uncertain whether CPM is impaired and TSP facilitated in patients with WAD and NSNP. PERSPECTIVE: This review and meta-analysis present the current evidence on CPM and TSP in patients with WAD and NSNP. Standardization of measurement methodology is needed to draw clear conclusions. Subsequently, future studies should investigate the clinical relevance of these measurements as prognostic variables or predictors of treatment success.

Central Sensitization: The Missing Link Between Psychological Distress and Poor Outcome Following Primary Total Knee Arthroplasty.

BACKGROUND: While preoperative psychological distress is known to predict risk for worse total knee arthroplasty (TKA) outcomes, distress may be too broad and nonspecific a predictor in isolation. We tested whether there are distinct preoperative TKA patient types based jointly on psychological status and measures of altered pain processing that predict adverse clinical outcomes. METHODS: In 112 TKA patients, we preoperatively assessed psychological status (depression, anxiety, and catastrophizing) and altered pain processing via a simple quantitative sensory testing protocol capturing peripheral and central pain sensitization. Outcomes (pain, function, opioid use) were prospectively evaluated at 6 weeks and 6 months after TKA. Cluster analyses were used to empirically identify TKA patient subgroups. RESULTS: There were 3 distinct preoperative TKA patient subgroups identified from the cluster analysis. A low-risk (LR) group was characterized by low psychological distress and low peripheral and central sensitization. In addition, 2 subgroups with similarly elevated preoperative psychological distress were identified, differing by pain processing alterations observed: high-risk centralized pain and high-risk peripheral pain. Relative to LR patients, high-risk centralized pain patients displayed significantly worse function and greater opioid use at 6 months after TKA (P values <.05). The LR and high-risk peripheral pain patient subgroups had similar 6-month outcomes (P values >.05). CONCLUSIONS: Among patients who have psychological comorbidity, only patients who have central sensitization were at elevated risk for poor functional outcomes and increased opioid use. Central sensitization may be the missing link between psychological comorbidity and poor TKA clinical outcomes. Preoperative testing for central sensitization may have clinical utility for improving risk stratification in TKA patients who have psychosocial risk factors.

The association between mechanical temporal summation, state anxiety at baseline, and persistent low back pain: a 12-month prospective cohort study.

BACKGROUND: Persons with acute low back pain (LBP) have a good prognosis for regaining function, while pain often persists. Neurobiological and psychosocial factors are recognized to amplify pain responses, as reported for central sensitization. This study investigated the combination of mechanical temporal summation (TS) chosen to characterize central sensitization and state anxiety representing a psychological factor and their association with persistent pain. METHODS: A longitudinal prospective cohort study including 176 participants aged between 18 and 65 with acute LBP was performed. The following independent variables were analyzed at baseline: The mechanical TS at the lower back, of whom the Wind-up ratio (WUR) was calculated, and the state anxiety level measured with the State and Trait Anxiety Inventory (STAI-S). The outcome pain intensity was assessed at baseline and 2,3,6 and 12 months after the onset of acute LBP with the Numeric Rating Scale 0-10 (NRS). Linear mixed models (LMM) were used to analyze the association of the independent variables with pain intensity over time. RESULTS: The mean baseline WUR was 1.3 (SD 0.6) for the right and 1.5 (SD 1.0) for the left side. STAI-S revealed a mean score of 43.1 (SD 5.2). Pain intensity was, on average, 5.4 points (SD 1.6) on the NRS and decreased over one year to a mean of 2.2 (SD 2.4). After one year, 56% of the participants still experienced pain. The LMM revealed a considerable variation, as seen in large confidence intervals. Therefore, associations of the independent variables (WUR and STAI-S) with the course of the outcome pain intensity over one year were not established. CONCLUSION: This investigation did not reveal an association of mechanical TS and state anxiety at baseline with pain intensity during the one-year measurement period. Pain persistence, mediated by central sensitization, is a complex mechanism that single mechanical TS and state anxiety cannot capture.

The enigmatic HCN channels: A cellular neurophysiology perspective.

What physiological role does a slow hyperpolarization-activated ion channel with mixed cation selectivity play in the fast world of neuronal action potentials that are driven by depolarization? That puzzling question has piqued the curiosity of physiology enthusiasts about the hyperpolarization-activated cyclic nucleotide-gated (HCN) channels, which are widely expressed across the body and especially in neurons. In this review, we emphasize the need to assess HCN channels from the perspective of how they respond to time-varying signals, while also accounting for their interactions with other co-expressing channels and receptors. First, we illustrate how the unique structural and functional characteristics of HCN channels allow them to mediate a slow negative feedback loop in the neurons that they express in. We present the several physiological implications of this negative feedback loop to neuronal response characteristics including neuronal gain, voltage sag and rebound, temporal summation, membrane potential resonance, inductive phase lead, spike triggered average, and coincidence detection. Next, we argue that the overall impact of HCN channels on neuronal physiology critically relies on their interactions with other co-expressing channels and receptors. Interactions with other channels allow HCN channels to mediate intrinsic oscillations, earning them the "pacemaker channel" moniker, and to regulate spike frequency adaptation, plateau potentials, neurotransmitter release from presynaptic terminals, and spike initiation at the axonal initial segment. We also explore the impact of spatially non-homogeneous subcellular distributions of HCN channels in different neuronal subtypes and their interactions with other channels and receptors. Finally, we discuss how plasticity in HCN channels is widely prevalent and can mediate different encoding, homeostatic, and neuroprotective functions in a neuron. In summary, we argue that HCN channels form an important class of channels that mediate a diversity of neuronal functions owing to their unique gating kinetics that made them a puzzle in the first place.

Temporal Summation of the Thermal Grill Illusion is Comparable to That Observed Following Noxious Heat.

The thermal grill illusion (TGI) describes a peculiar or even painful percept caused by non-noxious, interlaced warm and cold stimuli. It involves the glutamatergic system and is affected in putatively nociplastic syndromes such as fibromyalgia. The glutamatergic system is also involved in wind-up, that is, the increased activation of spinal neurons following repeated noxious stimulation leading to a temporal summation of perceived stimulus intensity. Here we combined both stimulation methods to further investigate whether non-noxious stimuli as employed in the TGI can lead to a similar summation of perceived stimulus intensity. In an experiment using a full crossover within-subjects design, 35 healthy volunteers received repeated stimuli, either in a thermal grill configuration or simply noxious heat. Both modalities were presented as sequences of 1 lead-in contact, followed by 11 consecutive contacts (each between 1.5 and 3 seconds), with either fast repetition ("wind-up" condition), or 2 slow-repeating control conditions. The main analyses concerned the relative pre-to-post sequence changes to quantify putatively wind-up-related effects. Pain ratings and skin conductance level (SCL) increased more strongly in "wind-up" than in control conditions. Interestingly, wind-up-related effects were of the same magnitude in TGI as compared to the pain control modality. Further, contact-by-contact SCL tracked how the effect emerged over time. These results indicate that although TGI does not involve noxious stimuli it is amenable to temporal summation and wind-up-like processes. Since both phenomena involve the glutamatergic system, the combination of wind-up with the TGI could yield a promising tool for the investigation of chronic pain conditions. PERSPECTIVE: Using thermal stimuli in an experimental protocol to combine 1) the TGI (painful or peculiar percept from simultaneous cold/warm stimulation) and 2) wind-up (increase in stimulus intensity after repeated exposure) holds promise to investigate pain and thermoceptive mechanisms, and chronic pain conditions.

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. PERSPECTIVE: This 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.

Association of mechanical temporal summation of pain with muscle co-contraction during walking in people with knee osteoarthritis.

BACKGROUND: People with knee osteoarthritis walk with excessive muscle co-contraction that can accelerate disease progression. Central pain sensitization is common in people with knee osteoarthritis and may be related to walking patterns. The objective of this study was to examine the relation of central pain sensitization with muscle co-contraction during walking in people with knee osteoarthritis. METHODS: This study reports secondary analysis from baseline data of two clinical trials (n = 90 participants with knee osteoarthritis). The presence of central pain sensitization was measured by mechanical temporal summation at the patella and the wrist. Quadriceps and hamstrings activation was assessed using surface electromyography during walking at self-selected and fast paces. Muscle co-contraction indices for vastus medialis-medial hamstrings and vastus lateralis-lateral hamstrings muscle pairs were calculated during stance phases. Co-contraction outcomes were compared between people with and without mechanical temporal summation at each site, adjusting for age, sex, and body mass index. FINDINGS: People with mechanical temporal summation at the knee had greater vastus lateralis-lateral hamstrings co-contraction while walking at a fast pace (P = 0.04). None of the other differences was statistically significant, but the overall trends and effect sizes indicated greater co-contraction in people with temporal summation at the knee irrespective of gait phase, walking speed, or muscle pairs. INTERPRETATION: Central pain sensitization, assessed as mechanical temporal summation at the knee, is related to greater knee muscle co-contraction during fast walking in people with knee osteoarthritis. Thus, mitigating central sensitization may be an interventional target to reduce muscle co-contraction for people with knee osteoarthritis.

Interplay between noxious heat sensitivity and temporal summation magnitude in patients with fibromyalgia and long-term opioid use.

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