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.

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.

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 < .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 ≥ .05). All interventions significantly decreased the negative affect of the Positive and Negative Affect Schedule (all P < .05). CONCLUSIONS: Motor imagery combined with virtual reality exerted hypoalgesic and affective-improvement effects similar to those of actual exercise. CLINICAL TRIALS REGISTRATION: The study was enrolled in the UMIN Clinical Trials Registry (registration number: UMIN000046095). The website for registration information is https://center6.umin.ac.jp/cgi-open-bin/ctr_e/ctr_view.cgi?recptno=R000052614.

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.

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.

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.

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.

Painful Cutaneous Laser Stimulation for Temporal Summation of Pain Assessment.

Variability in pain sensitivity arises not only from the differences in peripheral sensory receptors but also from the differences in central nervous system (CNS) pain inhibition and facilitation mechanisms. Temporal summation of pain (TSP) is an experimental protocol commonly used in human studies of pain facilitation but is susceptible to confounding when elicited with the skin-contact thermode, which adds the responses of touch-related Aß low-threshold mechanoreceptors to nociceptive receptors. In the present study, we evaluate an alternative method involving the use of a contactless cutaneous laser for TSP assessment. We show that repetitive laser stimulations with a one second inter-stimulus interval evoked reliable TSP responses in a significant proportion of healthy subjects (N = 36). Female subjects (N = 18) reported greater TSP responses than male subjects confirming earlier studies of sex differences in central nociceptive excitability. Furthermore, repetitive laser stimulations during TSP induction elicited increased time-frequency electroencephalography (EEG) responses. The present study demonstrates that repetitive laser stimulation may be an alternative to skin-contact methods for TSP assessment in patients and healthy controls. PERSPECTIVE: Temporal summation of pain (TSP) is an experimental protocol commonly used in human studies of pain facilitation. We show that contactless cutaneous laser stimulation is a reliable alternative to the skin contact approaches during TSP assessment.

Cortical activity during the wind-up of flexion reflex and pain: a magnetoencephalographic study using time-frequency analysis.

Wind-up is a nociceptive-specific phenomenon in which pain sensations are facilitated, in a frequency-dependent manner, by the repeated application of noxious stimuli of constant intensity, with invariant tactile sensations. Thus, cortical activities during wind-up could be an alteration associated with pain potentiation. We aimed to investigate somatosensory-evoked cortical responses and induced brain oscillations during wind-up by recording magnetoencephalograms. Wind-up was produced by the application of 11 consecutive electrical stimuli to the sural nerve, repeated at a frequency of 1 Hz without varying the intensity. The augmentation of flexion reflexes and pain rating scores were measured simultaneously as an index of wind-up. In the time-frequency analyses, the γ-band late event-related synchronization and the ß-band event-related desynchronization were observed in the primary somatosensory region and the bilateral operculo-insular region, respectively. Repetitive exposure to the stimuli enhanced these activities, along with an increase in the flexion reflex magnitude. The evoked cortical activity reflected novelty, with no alteration to these repetitive stimuli. Observed oscillations enhanced by repetitive stimulation at a constant intensity could reflect a pain mechanism associated with wind-up.

Central sensitization in CRPS patients with widespread pain: a cross-sectional study.

OBJECTIVE: Widespread pain hypersensitivity and enhanced temporal summation of pain (TSP) are commonly reported in patients with complex regional pain syndrome (CRPS) and discussed as proxies for central sensitization. This study aimed to directly relate such signs of neuronal hyperexcitability to the pain phenotype of CRPS patients. METHODS: Twenty-one CRPS patients and 20 healthy controls (HC) were recruited. The pain phenotype including spatial pain extent (assessed in % body surface) and intensity were assessed and related to widespread pain hypersensitivity, TSP, and psychological factors. Quantitative sensory testing (QST) was performed in the affected, the contralateral and a remote (control) area. RESULTS: CRPS patients showed decreased pressure pain thresholds in all tested areas (affected: t(34) = 4.98, P < .001, contralateral: t(35) = 3.19, P = .005, control: t(31) = 2.65, P = .012). Additionally, patients showed increased TSP in the affected area (F(3,111) = 4.57, P = .009) compared to HC. TSP was even more enhanced in patients with a high compared to a low spatial pain extent (F(3,51) = 5.67, P = .008), suggesting pronounced spinal sensitization in patients with extended pain patterns. Furthermore, the spatial pain extent positively correlated with the Bath Body Perception Disturbance Scale (ρ = 0.491; P = .048). CONCLUSIONS: Overall, we provide evidence that the pain phenotype in CRPS, that is, spatial pain extent, might be related to sensitization mechanism within the central nociceptive system. This study points towards central neuronal excitability as a potential therapeutic target in patients with more widespread CRPS.

The Effects of Recovery Sleep on Experimental Pain.

Recent research suggests that recovery sleep (RS) has the potential to restore pain sensitivity and modulation after hyperalgesia due to preceding sleep deprivation. However, it has not yet been systematically examined whether the restoration of these pain parameters is driven by sleep characteristics of RS. Thus, the present study assessed changes in experimental pain during RS after total sleep deprivation (TSD) to test whether RS parameters predicted the restoration of the pain system. Thirty healthy participants completed one night of habitual sleep, one night of TSD and a subsequent recovery night. At-home sleep during baseline and recovery was assessed using portable polysomnography and a questionnaire. Before and after each night pressure pain thresholds (PPTs), temporal pain summation (TSP) and conditioned pain modulation (CPM) were assessed. PPTs decreased after TSD and increased following RS, indicating a restoration of pain sensitivity after hyperalgesia. RS characteristics did not predict this restoration, suggesting other mechanisms (eg, changes in serotonergic activity) underlying the observed pain changes. TSP indicated a lack of effect of experimental sleep manipulations on excitatory processes whereas CPM lacked sufficient reliability to investigate inhibitory processes. Thus, results indicate moderate effects of sleep manipulations on pain sensitivity, but not on pain modulation. PERSPECTIVE: This article highlights the potential of recovery sleep to let pain thresholds return to normal following their decrease after a night of total sleep deprivation. In contrast, endogenous pain modulation (temporal pain summation, conditioned pain modulation) was not affected by sleep deprivation and recovery sleep.

Inter-subject variability of pleasant pain relief using a data-driven approach in healthy volunteers.

Background: The offset of a painful and unpleasant sensation can elicit pleasure. This phenomenon, namely pleasant pain relief (PPR), is attracting growing interest in research. While the cold pressor test (CPT) has been frequently used to study the inhibition of pain by the administration of another painful stimulation (inhibitory conditioned pain modulation; ICPM), a preliminary study from our research team has shown that CPT can also elicit a robust and long-lasting PPR. However, its effects on pain relief and inhibition vary greatly between subjects. Although substantial research has been carried out on inter-individual variability in the case of ICPM, the same cannot be said of PPR. Therefore, the current study sought to identify clusters of healthy volunteers with similar dynamic pain responses during the CPT, using a data-driven approach, and to investigate the inter-subject variability for PPR and ICPM. Methods: One hundred and twenty-two healthy volunteers were recruited. A sequential ICPM paradigm was carried out with CPT (water at 10°C) and a Peltier Thermode to evaluate pain intensity and unpleasantness. Moreover, PPR was measured for four minutes at CPT offset. Statistical analyses were performed using group-based trajectory modelling. Results: Four trajectories (groups) were identified for CPT pain intensity and unpleasantness ratings with varying levels of tonic pain and pain sensitization (e.g., temporal summation). PPR scores were correlated with both pain ratings trajectories (p < 0.001). On the other hand, no differences were found between groups regarding ICPM efficacy (percentage pain inhibition). Discussion: This study has provided a first step into the investigation of PPR and ICPM interindividual variability. Using a data-driven approach, it was shown that PPR at CPT offset differs between clusters of participants identified based on dynamic pain intensity and unpleasantness responses from CPT. Thus, it was brought to light that both the levels of tonic pain and pain sensitization underlie individual differences in PPR. The lack of correlation between CPT pain trajectories and ICPM efficacy may be explained by the hypotheses that eliciting ICPM requires only a certain threshold of stimulation which doesn't need to be noxious. In the future, studies on the inter-subject variability of PPR in large samples of chronic pain patients are warranted.

Effects of Exercise-Induced Hypoalgesia at Different Aerobic Exercise Intensities in Healthy Young Adults.

Purpose: Exercise-induced hypoalgesia (EIH) is a reduction in pain sensitivity that occurs following a single bout of exercise. However, little research has compared the EIH effects of exercise at different intensities, including low intensity, in the same participant. It is unclear as to which exercise intensities demonstrate EIH more effectively. The aim of this study was to examine and compare the effect of different intensities of exercise on pain sensitivity in the same participant. Methods: We included 73 healthy young adult volunteers (35 female and 38 male) in this experimental cross-over study. Each participant completed four experimental sessions of 30 min, consisting of aerobic exercise at 30% heart rate reserve (HRR), aerobic exercise at 50% HRR, aerobic exercise at 70% HRR, and quiet rest. EIH was assessed using the pressure pain threshold (PPT) and temporal summation of pain (TSP) in the quadriceps, biceps, and trapezius. Results: Low- and moderate-intensity exercise increased the multisegmental PPT and reduced TSP (all P < 0.05). High-intensity exercise increased the multisegmental PPT (all P < 0.05), but decreased TSP in only the quadriceps and biceps (P < 0.05), not the trapezius (P = 0.13). We found no difference in relative PPT and TSP changes between exercise intensities (P > 0.05) except for relative PPT change at the quadriceps (P < 0.05). Conclusion: Our results show that not only moderate- and high-intensity exercise, but also low-intensity exercise can produce a hypoalgesic response.

Predictive Value of Pain Sensitization Associated with Response to Exercise Therapy in Patients with Knee Osteoarthritis: A Prospective Cohort Study.

Purpose: Knee osteoarthritis (KOA) is a degenerative disease with inflammation, becoming persistent as it progresses, resulting in reduced quality of life. Exercise is the recommended treatment for KOA; however, the extent of pain reduction with exercise is heterogeneous and the prognostic implications of baseline factors in patients undergoing exercise are still unknown. This study examined the association between the response to exercise therapy and clinical outcomes, radiologic severity, and pain sensitization, and investigated the optimal predictive value for the effectiveness of exercise. Patients and Methods: Demographics, radiologic severity, pressure pain threshold (PPT), and temporal summation of pain (TSP) at the knee, tibia, and forearm were assessed at baseline. The pain numeric rating scale (NRS) was assessed before and after 12 weeks of exercise. Patients were divided into responder/non-responder groups according to recommended criteria: responder, ≥30% reduction in pain; non-responder, <30% reduction in pain, and each variable was compared between the groups. The area under the curve (AUC) and cutoff points were determined by receiver operating characteristic curve analysis. Results: Sixty-five patients were categorized as responders and 26 as non-responders. In the non-responder group, baseline NRS (P<0.01), pain duration (P<0.01), and TSP at the knee (P<0.001) and tibia (P<0.05) were significantly higher, and PPT at the knee (P<0.001), tibia (P<0.001), and forearm (P<0.001) were significantly lower, than those in the responder group; however, no significant differences between groups were found in other demographics and radiologic severity. The variables that showed moderate or better predictive ability (AUC≥0.7) were PPT at the knee (cutoff points: 241.5 kPa), tibia (307.5 kPa), forearm (318.5 kPa), and TSP at the knee (15.5 mm). Conclusion: Our findings suggest that pain sensitization is associated with the response to exercise therapy. Furthermore, we provide clinically predictive values for PPT and TSP in predicting the outcome to exercise in KOA.

Detection of altered pain facilitatory and inhibitory mechanisms in patients with knee osteoarthritis by using a simple bedside tool kit (QuantiPain).

Purpose: Altered pain facilitatory and inhibitory mechanisms have been recognized as an important manifestation in patients with chronic pain, and quantitative sensory testing (QST) can act as a proxy for this process. We have recently developed a simple bedside QST tool kit (QuantiPain) for more clinical use. The purpose of this study was to investigate its test-retest reliability and to evaluate its validity compared with the laboratory-based QST protocols in patients with knee osteoarthritis (OA). Methods: QuantiPain consists of 3 items: "pressure algometer" (for pressure pain thresholds [PPTs]), "pinprick" (for temporal summation of pain [TSP]), and "conditioning clamp" (for conditioned pain modulation [CPM]). In experiment-A, intrarater and interrater test-retest reliabilities were investigated in 21 young healthy subjects by using interclass correlation coefficient (ICC). In experiment-B, 40 unilateral painful patients with OA and 40 age-matched, healthy control subjects were included to compare the bedside tool kit against the computerized pressure algometry. Results: In experiment-A, excellent to moderate intrarater and interrater reliabilities were achieved in PPT and TSP (ICC: 0.60-0.92) while the agreements of CPM were good to poor (ICC: 0.37-0.80). In experiment-B, localized and widespread decrease of PPT, facilitated TSP, and impaired CPM was found by using the bedside tool kit in patients with OA compared with controls (P < 0.05). The data were significantly correlated with the established laboratory-based tools (R = 0.281-0.848, P < 0.05). Conclusion: QuantiPain demonstrated acceptable test-retest reliability and assessment validity with the sensitivity to separate patients with painful OA from controls, which has a potential to create more practical approach for quantifying altered pain mechanisms in clinical settings.

Phenotyping Chronic Musculoskeletal Pain in Male and Female Adolescents: Psychosocial Profiles, Somatosensory Profiles and Pain Modulatory Profiles.

PURPOSE: A major limitation in treatment outcomes for chronic pain is the heterogeneity of the population. Therefore, a personalized approach to the assessment and treatment of children and adolescents with chronic pain conditions is needed. The objective of the study was to subgroup pediatric patients with chronic MSK pain that will be phenotypically different from each other based on their psychosocial profile, somatosensory function, and pain modulation. PATIENTS AND METHODS: This observational cohort study recruited 302 adolescents (10-18 years) with chronic musculoskeletal pain and 80 age-matched controls. After validated self-report questionnaires on psychosocial factors were completed, quantitative sensory tests (QST) and conditioned pain modulation (CPM) were performed. RESULTS: Three psychosocial subgroups were identified: adaptive pain (n=125), high pain dysfunctional (n=115), high somatic symptoms (n=62). Based on QST, four somatosensory profiles were observed: normal QST (n=155), thermal hyperalgesia (n=98), mechanical hyperalgesia (n=34) and sensory loss (n=15). Based on CPM and temporal summation of pain (TSP), four distinct groups were formed, dysfunctional central processing group (n=27) had suboptimal CPM and present TSP, dysfunctional inhibition group (n=136) had suboptimal CPM and absent TSP, facilitation group (n=18) had optimal CPM and present TSP, and functional central processing (n=112) had optimal CPM and absent TSP. A significant association between the psychosocial and somatosensory profiles. However, no association was observed between the psychosocial or somatosensory profiles and pain modulatory profiles. CONCLUSION: Our results provide evidence that adolescents with chronic musculoskeletal pain are a heterogenous population comprising subgroups that may reflect distinct mechanisms and may benefit from different treatment approaches. The combination of screening self-reported questionnaires, QST, and CPM facilitate subgrouping of adolescents with chronic MSK pain in the clinical context and may ultimately contribute to personalized therapy.

Both Gender and Agonistic Experience Affect Perceived Pain during the Cold Pressor Test.

BACKGROUND: Differences in pain perception in athletes have recently been highlighted in the literature. OBJECTIVES: To compare gender ratings of perceived pain in athletes with low and high agonistic experiences (N = 200) using the Cold Pressor Test (CPT). METHODS: A three-way repeated measures ANOVA to assess both the effects of the athletes' gender and lower vs. higher agonistic experiences in the intensity of perceived pain at the beginning of the cold box hand immersion (L0) and after a 90 s interval (L1). RESULTS: There was a statistically significant interaction effect between the level of the agonistic experience and gender in the two moments: p < 0.001; ηp2 = 0.266; F(1,49) = 9.771. Simple main effects analysis showed a significative difference for females at L0: F(1,99) = 93.567, p < 0.025, partial η2 = 0.302) and for males at L1: F(1,99) = 173.420, p < 0.025, partial η2 = 0.666. At the initial moment of CPT, the female athletes showed significantly higher perceived intensity than males, regardless of their experience level. After a 90 s interval, a significantly lower pain perception effect associated with the increased competitive experience of male athletes was observed. Female athletes did not appear to benefit from the experience effect on their pain tolerance. CONCLUSIONS: The study confirmed a significant difference in pain perception associated with the athletes' gender and agonistic experience. Separate explanations related to the pattern of pain inhibition and the acquired reduction in pain sensitivity are reported.

Association of Chronic Pain with Radiologic Severity and Central Sensitization in Hip Osteoarthritis Patients.

PURPOSE: Pain and joint deformity are the most common symptoms of hip osteoarthritis (OA). However, no significant association between pain and severity of radiographic lesions has been reported. Recently, central sensitization has been suggested as an underlying mechanism of pain in OA. We investigated the involvement of radiologic severity or central sensitization in the clinical manifestation of hip OA with various degrees of joint deformity. PATIENTS AND METHODS: We included 39 patients with hip OA and divided them into two groups according to the severity of the hip pain: strong/severe (numerical rating scale, NRS≥6) and mild/moderate (NRS<6). We assessed the radiologic severity of OA using the Kellgren-Lawrence (K-L) scale and minimum joint space width (mJSW). We conducted quantitative sensory testing (QST) that included pressure pain threshold (PPT) and temporal summation of pain (TSP) at hip, tibialis anterior (leg), and extensor carpi radialis longus (arm) on the affected side. We examined the difference of radiologic assessment and QST results between each group and the correlation of the NRS with the radiologic assessment and QST results. RESULTS: There was no significant difference in the K-L scale and mJSW between patients with strong/severe and mild/moderate joint pain. Strong/severe pain patients demonstrated a lower PPT at all measurement sites and higher TSP at the hip and leg than the mild/moderate pain patients. In addition, NRS was significantly negatively correlated with PPT and positively correlated with TSP at all measurement sites, but not with the K-L scale and mJSW. CONCLUSION: We reported no significant difference in radiologic severity between patients with strong/severe and mild/moderate joint pain. By contrast, we found a significant difference in central sensitization represented by QST between strong/severe and mild/moderate joint pain groups. These results suggest that central sensitization may be involved in the joint pain of patients with hip OA who complain of severe pain despite less severe joint deformity.

Sensitization in office workers with chronic neck pain in different pain conditions and intensities.

OBJECTIVES: Office workers with chronic neck pain demonstrates signs of widespread hyperalgesia, less efficient descending pain modulation, which could indicate sensitization of central pain pathways. No studies have assessed a wide variety of office workers with different chronic neck pain disorders and assessed the impact of pain intensity on assessments of central pain pathways. This study aimed to assessed pressure pain thresholds (PPTs), temporal summation of pain (TSP) and conditioned pain modulation (CPM) and to associate these with pain intensity and disability in subgroups of office workers. METHODS: One hundred-and-seventy-one office workers were distributed into groups of asymptomatic and chronic neck pain subjects. Chronic neck pain was categorized as chronic trapezius myalgia and chronic non-specific neck pain and as 'mild-pain' (Visual Analog Scale [VAS]≤3) and 'moderate-pain' (VAS>3) groups. PPTs, TSP, CPM, and Copenhagen Psychosocial Questionnaire II were assessed in all subjects. Neck Disability Index and Pain Catastrophizing Scale were assessed in all the symptomatic office workers. RESULTS: PPTs were lower in moderate pain (n=49) and chronic trapezius myalgia (n=56) compared with asymptomatic subjects (n=62, p<0.05). TSP was facilitated in moderate pain group compared with mild pain (n=60, p<0.0001) group and asymptomatic subjects (p<0.0001). No differences were found in CPM comparing the different groups (p<0.05). Multiple regression analysis identified Neck Disability Index and TSP as independent factors for prediction of pain intensity in chronic trapezius myalgia (R2=0.319) and chronic non-specific neck pain (R2=0.208). Somatic stress, stress and sleep as independent factors in chronic non-specific neck pain (R2=0.525), and stress in moderate pain group (R2=0.494) for the prediction of disability. CONCLUSIONS: Office workers with chronic trapezius myalgia and moderate pain intensity showed significant signs of widespread pressure hyperalgesia. Moreover, the moderate pain group demonstrated facilitated TSP indicating sensitization of central pain pathways. Neck Disability Index and TSP were independent predictors for pain intensity in pain groups. Sleep and stress were independent predictors for disability.

Comparison of Thermal and Electrical Modalities in the Assessment of Temporal Summation of Pain and Conditioned Pain Modulation.

Temporal summation of pain (TSP) and conditioned pain modulation (CPM) can be measured using a thermode and a cold pressor test (CPT). Unfortunately, these tools are complex, expensive, and are ill-suited for routine clinical assessments. Building on the results from an exploratory study that attempted to use transcutaneous electrical nerve stimulation (TENS) to measure CPM and TSP, the present study assesses whether a "new" TENS protocol can be used instead of the thermode and CPT to measure CPM and TSP. The objective of this study was to compare the thermode/CPT protocol with the new TENS protocol, by (1) measuring the association between the TSP evoked by the two protocols; (2) measuring the association between the CPM evoked by the two protocols; and by (3) assessing whether the two protocols successfully trigger TSP and CPM in a similar number of participants. We assessed TSP and CPM in 50 healthy participants, using our new TENS protocol and a thermode/CPT protocol (repeated measures and randomized order). In the TENS protocol, both the test stimulus (TS) and the conditioning stimulus (CS) were delivered using TENS; in the thermode/CPT protocol, the TS was delivered using a thermode and the CS consisted of a CPT. There was no association between the response evoked by the two protocols, neither for TSP nor for CPM. The number of participants showing TSP [49 with TENS and 29 with thermode (p < 0.001)] and CPM [16 with TENS and 30 with thermode (p = 0.01)] was different in both protocols. Our results suggest that response to one modality does not predict response to the other; as such, TENS cannot be used instead of a thermode/CPT protocol to assess TSP and CPM without significantly affecting the results. Moreover, while at first glance it appears that TENS is more effective than the thermode/CPT protocol to induce TSP, but less so to induce CPM, these results should be interpreted carefully. Indeed, TSP and CPM response appear to be modality-dependent as opposed to an absolute phenomenon, and the two protocols may tap into entirely different mechanisms, especially in the case of TSP.