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.

UNASSIGNED: To assess the effects of 5 different durations of electro-dry needling (EDN) on asymptomatic individuals\' pain response after repeated noxious thermal stimuli.
UNASSIGNED: Randomized, non-controlled intervention trial.
UNASSIGNED: University laboratory.
UNASSIGNED: Asymptomatic participants (N=50) were recruited for the study and randomized into 5 groups. There were 33 women with an average age of 26.8 (±4.8) years. To participate in the study, individuals had to be between the ages of 18 and 40, free of any musculoskeletal injury which prevented participation of daily activities, and not pregnant or trying to become pregnant.
UNASSIGNED: Participants were randomly assigned to receive 5 different durations of EDN: 10, 15, 20, 25, and 30 minutes. To perform the EDN, 2 monofilament needles were inserted lateral to the lumbar spinous processes of L3 and L5 on the right. Needles were left in situ with electrical stimulation at a frequency of 2 Hz and an amplitude which resulted in a 3 to 6 out of 10 intensity pain rating by the participant.
UNASSIGNED: The change in the magnitude of pain in response to repetitive heat-pulses before and after the EDN procedure.
UNASSIGNED: There was a significant reduction in the magnitude of pain in response across the groups after EDN (F(1,42)=94.12, P<.001, ƞp2=.691). However, the interaction between time and group was not significant (F(4,42)=1.019, P=.409, ƞp2=.088), indicating that no duration of EDN was superior to another in reducing temporal summation.
UNASSIGNED: This study suggests that in asymptomatic individuals, performing EDN beyond 10 minutes does not provide any additional benefits in the reduction of the magnitude of pain in response to thermal nociceptive stimuli. Additional study in symptomatic populations is required for generalizability in clinical settings.

Native Americans (NAs) are more likely to experience chronic pain than non-Hispanic Whites (NHWs); however, the proximate causes predisposing NAs to chronic pain remain elusive. Likely due to centuries of adversity, discrimination, and marginalization, NAs report greater psychological stress than NHWs, which may place them at risk for sleep problems, a well-established risk factor for chronic pain onset.
This study examined the effects of psychological stress and sleep problems on subjective and physiological measures of pain processing in NAs and NHWs.
Structural equation modeling was used to determine whether ethnicity (NA or NHW) was associated with psychological stress or sleep problems and whether these variables were related to conditioned pain modulation of pain perception (CPM-pain) and the nociceptive flexion reflex (CPM-NFR), temporal summation of pain (TS-pain) and NFR (TS-NFR), and pain tolerance in a sample of 302 (153 NAs) pain-free participants.
NAs experienced more psychological stress (Estimate = 0.027, p = .009) and sleep problems (Estimate = 1.375, p = .015) than NHWs. When controlling for age, sex, physical activity, BMI, and general health, NA ethnicity was no longer related to greater sleep problems. Psychological stress was also related to sleep problems (Estimate = 30.173, p = <.001) and psychological stress promoted sleep problems in NAs (indirect effect = 0.802, p = .014). In turn, sleep problems were associated with greater TS-pain (Estimate = 0.714, p = .004), but not other pain measures.
Sleep problems may contribute to chronic pain risk by facilitating pain perception without affecting facilitation of spinal neurons or endogenous inhibition of nociceptive processes. Since psychological stress promoted pain facilitation via enhanced sleep problems, efforts to reduce psychological stress and sleep problems among NAs may improve health outcomes.

BACKGROUND: Knee osteoarthritis (OA) is among the most common and disabling persistent pain conditions, with increasing prevalence and impact around the globe. In the U.S., the rising prevalence of knee OA has been paralleled by an increase in annual rates of total knee arthroplasty (TKA), a surgical treatment option for late-stage knee OA. While TKA outcomes are generally good, post-operative trajectories of pain and functional status vary substantially; a significant minority of patients report ongoing pain and impaired function following TKA. A number of studies have identified sets of biopsychosocial risk factors for poor post-TKA outcomes (e.g., comorbidities, negative affect, sensory sensitivity), but few prospective studies have systematically evaluated the unique and combined influence of a broad array of factors.
METHODS: This multi-site longitudinal cohort study investigated predictors of 6-month pain and functional outcomes following TKA. A wide spectrum of relevant biopsychosocial predictors was assessed preoperatively by medical history, patient-reported questionnaire, functional testing, and quantitative sensory testing in 248 patients undergoing TKA, and subsequently examined for their predictive capacity.
RESULTS: The majority of patients had mild or no pain at 6 months, and minimal pain-related impairment, but approximately 30% reported pain intensity ratings of 3/10 or higher. Reporting greater pain severity and dysfunction at 6 months post-TKA was predicted by higher preoperative levels of negative affect, prior pain history, opioid use, and disrupted sleep. Interestingly, lower levels of resilience-related \"positive\" psychosocial characteristics (i.e., lower agreeableness, lower social support) were among the strongest, most consistent predictors of poor outcomes in multivariable linear regression models. Maladaptive profiles of pain modulation (e.g., elevated temporal summation of pain), while not robust unique predictors, interacted with psychosocial risk factors such that the TKA patients with the most pain and dysfunction exhibited lower resilience and enhanced temporal summation of pain.
CONCLUSIONS: This study underscores the importance of considering psychosocial (particularly positively-oriented resilience variables) and sensory profiles, as well as their interaction, in understanding post-surgical pain trajectories.

Introduction: Quantitative sensory testing is frequently used in research to assess endogenous pain modulation mechanisms, such as Temporal Summation (TS) and Conditioned Pain Modulation (CPM), reflecting excitatory and inhibitory mechanisms, respectively. Numerous studies found that a dysregulation of these mechanisms is associated with chronic pain conditions. In turn, such a patient\'s \"profile\" (increased TS and/or weakened CPM) could be used to recommend different pharmacological treatments. However, the procedure to evaluate these mechanisms is time-consuming and requires expensive equipment that is not available in the clinical setting. In this study, we aim to identify psychological, physiological and socio-demographic markers that could serve as proxies to allow healthcare professionals to identify these pain phenotypes in clinic, and consequently optimize pharmacological treatments. Method: We aim to recruit a healthy participant cohort (n = 360) and a chronic pain patient cohort (n = 108). Independent variables will include psychological questionnaires, pain measurements, physiological measures and sociodemographic characteristics. Dependent variables will include TS and CPM, which will be measured using quantitative sensory testing in a single session. We will evaluate one prediction model and two validation models (for healthy and chronic pain participants) using multiple regression analysis between TS/CPM and our independent variables. The significance thresholds will be set at p = 0.05, respectively. Perspectives: This study will allow us to develop a predictive model to compute the pain modulation profile of individual patients based on their biopsychosocial characteristics. The development of the predictive model is the first step toward the overarching goal of providing clinicians with a set of quick and cheap tests, easily applicable in clinical practice to orient pharmacological treatments.

Native Americans (NAs) have higher pain rates than the general U.S. population. It has been found that increased central sensitization and reduced pain inhibition are pronociceptive processes that increase pain risk; yet, little attention has focused on the influence of psychosocial factors. Discrimination is a psychosocial factor associated with increased pain in other minoritized groups; however, it is unclear whether it also promotes pain in NAs. This study analyzed data from 269 healthy, pain-free participants (N = 134 non-Hispanic whites [NHWs], N = 135 NAs) from the Oklahoma Study of Native American Pain Risk. Experienced discrimination was measured using the Everyday Discrimination Scale (EDS). Nociceptive processes were measured via static measures of spinal sensitivity (nociceptive flexion reflex [NFR] threshold, 3-stimulation NFR threshold), temporal summation of pain (TS-Pain) and nociceptive flexion reflex (TS-NFR), and conditioned pain modulation of pain (CPM-Pain) and NFR (CPM-NFR). Results demonstrated that greater discrimination was associated with enhanced TS-NFR and impaired CPM-NFR but not static measures of spinal sensitivity or measures of pain modulation (TS-Pain, CPM-Pain). Although the effects of discrimination on outcomes were similar in both groups (not moderated by ethnicity), NAs experienced higher levels of discrimination and therefore discrimination mediated a relationship between ethnicity and impaired CPM-NFR. This indicates experienced discrimination may promote a pain risk phenotype in NAs that involves spinal sensitization resulting from impaired inhibition of spinal nociception without sensitization of pain experience. PERSPECTIVE: This study found that discrimination was associated with spinal sensitization and impaired descending inhibition of spinal nociception. These findings bolster our understanding of how social stressors experienced disproportionately by minoritized groups can contribute to pain outcomes.

Chronic fatigue syndrome (CFS) and fibromyalgia (FM) are both complex conditions that are challenging to treat. This may be related to an incomplete understanding of their pathophysiology, itself obfuscated by their heterogeneity. The symptomatic overlap between them and their common comorbidity suggests a shared vulnerability, which might be explained by central sensitisation.
19 CFS cases, 19 FM cases and 20 age and sex matched healthy controls (HC) were recruited primarily from secondary care clinics in London. Those with other pain disorders, psychiatric diagnoses and those taking centrally acting or opiate medications were excluded. Participants were asked to abstain from alcohol and over the counter analgaesia 48 h prior to assessment by static and dynamic quantitative sensory tests, including measures of temporal summation (TS) and conditioned pain modulation (CPM).
CS, as defined by the presence of both enhanced TS and inefficient CPM, was present in 16 (84%) CFS cases, 18 (95%) FM cases, and none of the HC (p < 0.001). Pressure pain thresholds were lower in CFS (Median222kPaIQR 146-311; p = 0.04) and FM cases (Median 189 kPa; IQR 129-272; p = 0.003) compared to HC (Median 311 kPa; IQR 245-377). FM cases differed from HC in cold-induced (FM = 22.6 °C (15.3-27.7) vs HC = 14.2 °C (9.0-20.5); p = 0.01) and heat-induced (FM = 38.0 °C (35.2-44.0) vs HC = 45.3 °C (40.1-46.8); p = 0.03) pain thresholds, where CFS cases did not.
Central sensitisation may be a common endophenotype in chronic fatigue syndrome and fibromyalgia. Further research should address whether central sensitisation is a cause or effect of these disorders.

BACKGROUND: Transcranial direct current stimulation (tDCS) of the motor cortex (M1) produces short-term inhibition of pain. Unihemispheric concurrent dual-site tDCS (UHCDS-tDCS) over the M1 and dorsolateral prefrontal cortex (DLPFC) has greater effects on cortical excitability than when applied alone, although its effect on pain is unknown. The aim of this study was to test if anodal UHCDS-tDCS over the M1 and DLPFC in healthy participants could potentiate conditioned pain modulation (CPM) and diminish pain temporal summation (TS).
METHODS: Thirty participants were randomized to receive a sequence of UHCDS-tDCS, M1-tDCS and sham-tDCS. A 20 min 0.1 mA/cm2 anodal or sham-tDCS intervention was applied to each participant during three test sessions, according to a triple-blind cross-over trial design. For the assessment of pain processing before and after tDCS intervention, the following tests were performed: tourniquet conditioned pain modulation (CPM), pressure pain temporal summation (TS), pressure pain thresholds (PPTs), pressure pain tolerance, mechanosensitivity and cold hyperalgesia. Motor function before and after tDCS intervention was assessed with a dynamometer to measure maximal isometric grip strength.
RESULTS: No statistically significant differences were found between groups for CPM, pressure pain TS, PPT, pressure pain tolerance, neural mechanosensitivity, cold hyperalgesia or grip strength (p > 0.05).
CONCLUSIONS: Neither UHCDS-tDCS nor M1-tDCS facilitated CPM or inhibited TS in healthy subjects following one intervention session.

Objectives Stretching is an intervention often used in various kinds of rehabilitation protocols and the effects on pain sensitivity has sparsely been investigated, especially when addressing potential effects on pain. The objective is to investigate the immediate effects of an axial and peripheral prolonged stretch on pressure pain sensitivity (PPT) and temporal summation (TS) on local and distal sites in healthy subjects. Methods Twenty-two healthy volunteers were recruited to participate in this pilot study. Two prolonged stretching protocols were performed: low back and wrist extensors stretches. PPT and pinprick TS were measured pre- and post-intervention at local and remote sites. Repeated measures analysis of variance (ANOVA) was used to examine the effects and significance of the interventions. Results The low back stretch induced an increase in PPT for both local and remote sites, and the wrist stretch produced a PPT increase only at the local site. TS did not change. Conclusions Low back stretching induced an increase in PPT at both local and remote sites whereas the wrist stretch only increased PPT locally, suggesting hypoalgesia at these sites. Further studies are needed to confirm the effect and mechanisms using randomised, controlled and parallel study design. Considering that pain sensitivity is different than clinical pain, results are difficult to extrapolate to clinical practice. Future studies testing clinical pain are needed to better understand the clinical implication of these results.

Adverse life experiences (ALEs) are associated with hyperalgesia and chronic pain, but the underlying mechanisms are poorly understood. One potential mechanism is hyperexcitability of spinal neurons (ie, central sensitization). Given that Native Americans (NAs) are more likely to have ALEs and to have a higher prevalence of chronic pain, the relationship between ALEs and spinal hyperexcitability might contribute to their pain risk. The present study assessed temporal summation of the nociceptive flexion reflex (TS-NFR; a correlate of spinal hyperexcitability) and pain (TS-Pain) in 246 healthy, pain-free non-Hispanic whites and NAs. The Life Events Checklist was used to assess the number of ALEs. Multilevel growth models were used to predict TS-NFR and TS-Pain, after controlling for age, perceived stress, psychological problems, negative and positive affect, and painful stimulus intensity. ALEs and negative affect were significantly associated with greater pain, but not enhanced TS-Pain. By contrast, ALEs were associated with enhanced TS-NFR. Race did not moderate these relationships. This finding implies that ALEs promote hyperalgesia as a result of increased spinal neuron excitability. Although relationships between ALEs and the nociceptive flexion reflex/pain were not stronger in NAs, given prior evidence that NAs experience more ALEs, this factor might contribute to the higher prevalence of chronic pain in NAs. PERSPECTIVE: This study found a dose-dependent relationship between ALEs and spinal neuron excitability. Although the relationship was not stronger in NAs than non-Hispanic whites, given prior evidence that NAs experience more ALEs, this could contribute to the higher prevalence of chronic pain in NAs.