Temporal Summation Of Pain Research Articles

Indicators of central sensitization in chronic neuropathic pain after spinal cord injury.

Central sensitization is considered a key mechanism underlying neuropathic pain (NP) after spinal cord injury (SCI). Two novel proxies for central sensitization were investigated in thoracic SCI subjects with (SCI-NP) and without NP (SCI-nonNP) compared to healthy controls (HC). Specifically, temporal summation of pain (TSP) was investigated by examining pain ratings during a 2-min tonic heat application to the volar forearm. Additionally, palmar heat-induced sympathetic skin responses (SSR) were recorded in order to reveal changes in pain-autonomic interaction above the lesion level. Pain extent was assessed as the percentage of the body area and the number of body regions being affected by NP. Enhanced TSP was observed in SCI-NP (+66%) compared to SCI-nonNP (-75%, p= 0.009) and HC (-59%, p= 0.021). In contrast, no group differences were found (p= 0.685) for SSR habituation. However, pain extent in SCI-NP was positively correlated with deficient SSR habituation (body area: r= 0.561, p= 0.024; body regions: r= 0.564, p= 0.023). These results support the value of TSP and heat-induced SSRs as proxies for central sensitization in widespread neuropathic pain syndromes after SCI. Measures of pain-autonomic interaction emerged as a promising tool for the objective investigation of sensitized neuronal states in chronic pain conditions. We present two surrogate readouts for central sensitization in neuropathic pain following SCI. On the one hand, temporal summation of tonic heat pain is enhanced in subjects with neuropathic pain. On the other hand, pain-autonomic interaction reveals potential advanced measures in chronic pain, as subjects with a high extent of neuropathic pain showed diminished habituation of pain-induced sympathetic measures. A possible implication for clinical practice is constituted by an improved assessment of neuronal hyperexcitability potentially enabling mechanism-based treatment.

Carpal tunnel surgery dampens thalamocortical and normalizes corticocortical functional connectivity.

Carpal tunnel syndrome is the most common entrapment neuropathy and is associated with altered brain function and structure. However, little is understood of the central mechanisms associated with its pain, symptom presentation, and treatment-related resolution. This longitudinal study evaluated carpal tunnel syndrome-related alterations in brain network communication and relationships to behavioural signs of central sensitization before and after carpal tunnel release surgery. We tested the hypothesis that carpal tunnel syndrome is associated with condition- and treatment-related plasticity in brain regions involved in somatosensation. We used quantitative sensory testing and clinical and pain questionnaires to assess sensory and pain function in 25 patients with carpal tunnel syndrome before (18 women, 7 men) and after (n = 16) surgery, and 25 sex- and age-matched healthy controls. We also acquired resting-state functional MRI to determine functional connectivity of two key nodes in the somatosensory system, the thalamus and primary somatosensory cortex. Seed-to-whole brain resting-state static functional connectivity analyses revealed abnormally low functional connectivity for the hand area of the primary somatosensory cortex with the contralateral somatosensory association cortex (supramarginal gyrus) before surgery (P < 0.01). After clinically effective surgery: (i) Primary somatosensory functional connectivity was normalized with the contralateral somatosensory association cortex and reduced with the dorsolateral prefrontal cortex (a region associated with cognitive and emotional modulation of pain) and primary visual areas (P < 0.001) from pre-op levels; and (ii) Functional connectivity of the thalamus with the primary somatosensory and motor cortices was attenuated from pre-op levels (P < 0.001) but did not correlate with temporal summation of pain (a behavioural measure of central sensitization) or clinical measures. This study is the first to reveal treatment-related neuroplasticity in resting-state functional connectivity of the somatosensory system in carpal tunnel syndrome. The findings of dysfunctional resting-state functional connectivity point to aberrant neural synchrony between the brain’s representation of the hand with regions involved in processing and integrating tactile and nociceptive stimuli and proprioception in carpal tunnel syndrome. Aberrant neural communication between the primary somatosensory hand area and the dorsolateral prefrontal cortex could reflect increased attention to pain, paraesthesia, and altered sensation in the hand. Finally, reduced thalamocortical functional connectivity after surgery may reflect central plasticity in response to the resolution of abnormal sensory signals from the periphery. Our findings support the concept of underlying brain contributions to this peripheral neuropathy, specifically aberrant thalamocortical and corticocortical communication, and point to potential central therapeutic targets to complement peripheral treatments.

Pain Sensitization and Neuropathic Pain-like Symptoms Associated with Effectiveness of Exercise Therapy in Patients with Hip and Knee Osteoarthritis.

Pain sensitization and neuropathic pain-like symptoms are some of the common pain symptoms in patients with lower limbs, including hip and knee, osteoarthritis (HOA/KOA). Exercise therapy has been the first-line treatment; however, the effects differ for each patient. This prospective cohort study investigated the relationship between the effectiveness of exercise therapy and pretreatment characteristics (radiologic severity, pain sensitization, and neuropathic pain-like symptoms) of patients with HOA/KOA. We assessed the pain intensity using a numerical rating scale (NRS) before and after 12 weeks of exercise therapy in patients with HOA/KOA (n = 101). Before treatment, the Kellgren–Lawrence (K-L) grade; minimum joint space width (mJSW); pressure pain threshold (PPT) and temporal summation of pain (TSP) at the affected joint, tibia, and forearm; Central Sensitization Inventory-9; and painDETECT questionnaire (PDQ) were assessed. Cluster analysis was based on the pretreatment NRS and change in NRS with exercise therapy to identify the subgroups of pain reduction. The pretreatment characteristics of each cluster were compared. According to the results of the cluster analyses, patients in cluster 1 had severe pain that did not improve after exercise therapy, patients in cluster 2 had severe pain that improved, and those in cluster 3 had mild pain that improved. The patients in cluster 1 exhibited lower PPT at all measurement sites, higher TSP at the affected joint, and higher PDQ scores than those in other clusters. There was no difference in the K-L grade and mJSW among the clusters. The subgroup with severe pain and pain sensitization or neuropathic pain-like symptoms at pretreatment, even with mild joint deformity, may have difficulty in achieving improvement in pain after 12 weeks of exercise therapy. These findings could be useful for prognosis prediction and for planning exercise therapy and combining with other treatment.

Chronic postoperative pain after total knee arthroplasty: The potential contributions of synovitis, pain sensitization and pain catastrophizing-An explorative study.

BackgroundA subset of osteoarthritis patients will experience chronic postoperative pain after total knee arthroplasty (TKA), but the source of pain is unclear. The aim of this exploratory study was to assess patients with and without postoperative pain after TKA using magnetic resonance imaging (MRI), quantitative sensory testing (QST), clinical assessment of pain and assessments of catastrophizing thoughts.MethodsForty‐six patients completed the 6‐month postoperative assessment. MRI findings were scored according to the MRI Osteoarthritis Knee Score recommendation for Hoffa synovitis, effusion size and bone marrow lesions. QST included assessment of pressure pain thresholds (PPTs), temporal summation of pain (TSP) and conditioned pain modulation (CPM). Pain catastrophizing was assessed using the Pain Catastrophizing Scale (PCS). Clinical pain assessment was conducted using a visual analogue scale (VAS, 0–10 cm), and groups of moderate‐to‐severe (VAS > 3) and none‐to‐mild postoperative pain (VAS ≤ 3) were identified.ResultsPatients with moderate‐to‐severe postoperative pain (N = 15) demonstrated higher grades of Hoffa synovitis (p < 0.001) and effusion size (p < 0.001), lower PPTs (p = 0.039), higher TSP (p = 0.001) and lower CPM (p = 0.014) when compared with patients with none‐to‐mild postoperative pain (N = 31). No significant difference was found in PCS scores between the two groups. Multiple linear regression models found synovitis (p = 0.036), effusion size (p = 0.003), TSP (p = 0.013) and PCS (p < 0.001) as independent parameters contributing to the postoperative pain intensity.ConclusionThese exploratory findings could indicate that chronic postoperative pain after TKA is a combination of joint‐related synovitis and effusion, sensitization of central pain mechanisms and potentially pain catastrophizing thoughts, but larger studies are needed to confirm this.SignificanceThe end‐stage treatment of knee osteoarthritis is total knee arthroplasty. Some patients experience chronic postoperative pain after total knee arthroplasty, but the mechanism for chronic postoperative pain is widely unknown. The current study indicates that higher levels postoperative of synovitis and effusion, higher temporal summation of pain and higher pain catastrophizing scores could be associated with higher chronic postoperative pain.

A simple, bed-side tool to assess evoked pressure pain intensity.

Existing equipment for quantitative sensory testing is generally expensive and not easily applicable inaclinical setting thus simple bed-side devices are warranted. Pressure hyperalgesia is a common finding in patients withmusculoskeletal pain and an experimental model is delayed-onset muscle soreness (DOMS). DOMS ischaracterised by muscle hyperalgesia and some studies report facilitation of temporal summation of pain. This study aimed to detect DOMS induced muscle hyperalgesia and temporal summation of pain using a newly developed bed-side quantitative sensory testing device to deliver standardised pressure. Twenty-two healthy participants participated in two sessions with the second session approximately 48h after baseline. Pressure pain intensities were assessed from the gastrocnemius muscle with four probes calibrated to apply 2, 4, 6 and 8kg, respectively. Temporal summation of pain (10 stimuli delivered at 0.5Hz using the 6kg probe) intensities were assessed from the same location. DOMS was evoked in the gastrocnemius muscle by an eccentric exercise. Sleepiness and physical activity were measured with the Epworth Sleepiness Scale and the Global Physical Activity Questionnaire to investigate if they were associated with the quantitative sensory testing measures. Pressure pain intensity was significantly increased 48h after induction of DOMS when compared to baseline for all four probes (p<0.05). Temporal summation of pain was not statistically significant affected by DOMS and sleep quality and physical activity did not associate with any of the measures. This study introduces a simple, bed-side assessment tool for the assessment of pressure pain intensity and hence hyperalgesia and temporal summation of pain.

Sex effects in the interaction of acute stress and pain perception.

A reciprocity between the stress and the pain system is recognized; however, the manner by which sex affects this reciprocity is unclear. Understanding the interactions of stress, pain, and sex may shed light on the apparent women's vulnerability to chronic pain, which often coexists with increased distress, and to affective disorders, which often coexist with chronic pain. The study's aim was to examine the effect of acute, validated, psychosocial stress on pain perception and modulation of women and men in a controlled manner. Participants were 82 women and 66 men. Heat-pain threshold, heat-pain tolerance, and pain modulation by temporal summation of pain (TSP), and pain adaptation were measured before and after exposure to the Montreal Imaging Stress Task (MIST) or to a sham task. The stress response was verified by perceived ratings of stress and anxiety, autonomic variables, and salivary cortisol. A significant stress response was obtained by the MIST among both sexes; however, women displayed a greater increase in perceived distress, and men displayed a greater increase in cortisol. Among women, TSP decreased and pain adaptation increased following the MIST, responses that were predicted by perceived distress levels. Among men, TSP increased following the MIST but was not predicted by the stress variables. In conclusion, acute stress manipulation seems to differentially affect both stress and pain responses of women and men: women exhibited stress-induced antinociception and men exhibited stress-induced pronociception. Higher perceived stress levels among women may trigger a temporary increase in pain inhibition mechanisms to serve evolutionary purposes.

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

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

The influence of exercise on clinical pain and pain mechanisms in patients with subacromial pain syndrome.

BackgroundFew studies have investigated the underlying mechanisms for unilateral subacromial pain syndrome (SAPS). Therefore, this study examined (1) if 8‐weeks of exercise could modulate clinical pain or temporal summation of pain (TSP), conditioned pain modulation (CPM), and exercise‐induced hypoalgesia (EIH) and (2) if any of these parameters could predict the effect of 8‐weeks of exercise in patients with unilateral SAPS.MethodsThirty‐seven patients completed a progressive abduction exercise program every other day for 8‐weeks. Worst shoulder pain in full abduction was rated on a numeric rating scale (NRS). Pain pressure thresholds (PPTs), TSP, CPM, EIH, Shoulder Pain and Disability Index (SPADI), Pain Catastrophizing Scale (PCS), PainDETECT questionnaire (PD‐Q), Pain Self‐Efficacy Questionnaire (PSE‐Q) and Pittsburgh Sleep Quality Index (PSQI) were assessed before and after intervention.ResultsThe intervention improved worst pain intensity (p < 0.001), increased the CPM (p < 0.001), improved the sleep scores (p < 0.005) and reduced the PainDETECT ratings (p < 0.001). No changes were observed in PPT, TSP, EIH, SPADI, PCS and PSE‐Q (all p > 0.05). In a linear regression, the combination of all baseline parameters predicted 23.2% variance in absolute change in pain after 8 weeks. Applying backwards elimination to the linear regression yielded that baseline pain intensity combined with TSP predicted 33.8% variance.ConclusionThis explorative study suggested reduction in pain, improved sleep quality and increased CPM after 8‐weeks of exercise. Furthermore, the results suggests that low pain intensity and high TSP scores (indicative for pain sensitisation) may predict a lack of pain improvement after exercise.

Sleep Problems Mediate the Relationship Between Psychosocial Stress and Pain Facilitation in Native Americans: A Structural Equation Modeling Analysis from the Oklahoma Study of Native American Pain Risk.

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.

Sociocultural Context and Pre-Clinical Pain Facilitation: Multiple Dimensions of Racialized Discrimination Experienced by Latinx Americans are Associated With Enhanced Temporal Summation of Pain

The experiences of injustice and their impacts on pain among Latinx Americans are overlooked and understudied. Multidimensional and consequential experiences of racialized discrimination are common for Latinx Americans but have not been considered as factors relevant for enhanced pain experience or risk. In this study, we focused on the experiences of Latinx Americans living in Texas by assessing multiple dimensions of racialized discrimination (total lifetime discrimination, racialized exclusion, stigmatization, discrimination in the workplace or school, and racism-related threat and aggression) and a laboratory marker of central sensitization of pain (temporal summation of mechanical pain, MTS). Among 120 adults who did not have chronic pain, nearly all (94.2%) experienced racialized discrimination. Accumulated lifetime experience of racialized discrimination, as well as the frequency of each dimension of discrimination assessed, was associated with greater MTS. Results suggest that a process of discrimination-related central sensitization may start early, and may reflect enhanced pain experiences and pre-clinical chronic pain risk. Though replication is needed, results also indicate the discrimination and pain burden among Latinx Texans, and Latinx Americans broadly, are likely under-represented in the scientific literature. PerspectiveRacialized discrimination is multidimensional. Latinx Texans experience frequent discrimination that is associated with enhanced temporal summation of pain in the laboratory. Results indicate the importance of societal factors in pain processing and may reflect a mechanism of racism-related pre-clinical central sensitization observable before chronic pain onset.

The effect of duloxetine on mechanistic pain profiles, cognitive factors and clinical pain in patients with painful knee osteoarthritis-A randomized, double-blind, placebo-controlled, crossover study.

BackgroundDuloxetine is indicated in the management of pain in osteoarthritis. Evidence suggests that duloxetine modulates central pain mechanisms and cognitive factors, and these factors are assumed contributing to the analgesic effect. This proof‐of‐mechanism, randomized, placebo‐controlled, crossover, double‐blinded trial evaluated the effect of duloxetine on quantitative sensory testing (QST), cognitive factors and clinical pain in patients with osteoarthritis and to predict the analgesic effect.MethodsTwenty‐five patients completed this cross‐over study with either 18‐week duloxetine (maximum 60 mg/daily) followed by placebo or vice‐versa. Pressure pain thresholds, temporal summation of pain and conditioned pain modulation were assessed using cuff algometry. The Hospital Anxiety and Depression Scale and the Pain Catastrophizing Scale evaluated cognitive factors. Clinical pain was assessed using Brief Pain Inventory and Western Ontario and McMaster Universities Osteoarthritis Index. Linear regression models were used to predict the analgesic effect of duloxetine.ResultsDepending on the clinical pain outcome, 40%–68% of patients were classified as responders to duloxetine. Linear regression models predicted the analgesic effect (predictive value of 45%–75% depending on clinical pain outcome parameter) using a combination of pretreatment QST parameters, cognitive factors and clinical pain. No significant changes were found for QST, cognitive factors or clinical pain on a group level when comparing duloxetine to placebo.ConclusionA combination of pretreatment QST, cognitive factors and clinical pain was able to predict the analgesic response of duloxetine. However, in this relatively small study, duloxetine did not selectively modulate QST, cognitive factors or clinical pain intensity when compared with placebo.SignificanceDuloxetine is proposed as a treatment for chronic pain. Pre‐clinical trials suggest that duloxetine provides analgesia through modulation of descending pain inhibitory pathways or through improvements in cognitive factors. The current study demonstrates that pretreatment mechanistic pain profiling, cognitive factors and clinical pain can predict the analgesic effect of duloxetine and that only a subset of patients might benefit from duloxetine treatment.

POS1021 THE EFFECT OF CANNABIDIOL ON QUANTITATIVE SENSORY TESTING PARAMETERS IN PATIENTS WITH HAND OSTEOARTHRITIS AND PSORIATIC ARTHRITIS: A RANDOMIZED DOUBLE-BLIND PLACEBO-CONTROLLED TRIAL

BackgroundCannabidiol (CBD) has been proposed as an analgesic/anti-inflammatory treatment modality for joint pain. This study is based on a randomised, placebo controlled, double blind study (NORDCAN), investigating the effect of CBD in patients with painful hand osteoarthritis or psoriatic arthritis [1].ObjectivesThe aim of the present study was to investigate the effect of CBD on quantitative sensory testing (QST) parameters.MethodsThe present randomised, placebo controlled, double blind study included 128 patients with hand osteoarthritis or psoriatic arthritis with chronic pain of moderate intensity. The trial compared 12 weeks of 20-30 mg CBD treatment with placebo. The QST parameters were assessed at baseline and after treatment. Pressure pain thresholds was measured at the most painful finger joint (local site) and the shin of the right leg (distal non-painful site). Temporal summation of pain and conditioned pain modulation were assessed using computer-controlled cuff algometry with the tourniquets on lower leg at the level of the upper portion of the gastrocnemius.ResultsBaseline characteristics (demographics and pain) for the CBD treated group and placebo group were comparable. No significant differences were observed in QST variables between baseline and end of treatment when comparing CBD and placebo.ConclusionNo differences in modulation in QST parameters were demonstrated in patients in treatment with 20-30 mg CBD compared to placebo. Further studies of patients with rheumatic diseases treated with different dosage of CBD are needed to clarify the effect of CBD on pain in this patient group.

Traditional acupuncture and laser acupuncture in chronic nonspecific neck pain: study protocol for a randomized controlled trial

BackgroundNonspecific neck pain is a multifactorial and very common condition in adult individuals, traditional acupuncture (TA) and laser acupuncture (LA) may be treatment options for certain individuals in such a condition. However, no reports were found in the literature comparing the effectiveness of TA and LA in cases of chronic nonspecific neck pain. Therefore, the aim of the present study is to investigate the effectiveness of TA and LA therapies in individuals with chronic nonspecific neck pain, noting which one is more efficient for this condition. The result of this research will have direct implications for pain management and, consequently, may benefit individuals suffering from nonspecific chronic neck pain.Methods/designThis will be a controlled and randomized clinical trial. Eighty-four individuals will be recruited and distributed equally and randomly into 3 groups: TA (which will receive the acupuncture treatment with needles), LA (which will receive the laser acupuncture treatment), and Sham (who will receive the placebo intervention). The acupuncture points (Tianzhu, Fengchi, Jianjing, and Jianzhongshu) will be stimulated bilaterally. The primary outcome will be pain intensity, determined using the Numerical Rating Scale. The secondary outcomes will be pressure pain threshold, temporal summation of pain, conditioned pain modulation, use of analgesic medicines after treatment, and the global perceived effect scale. The assessments will be performed immediately before and after the treatment, which will be a single session, at the follow-up and 1 month after the end of the treatments; evaluation will be made of the pain intensity and the global perceived effect. Statistical analysis of the data obtained will consider a significance level of p < 0.05.DiscussionThis study will provide evidence concerning the effects of LA treatment, in comparison with TA and sham intervention, leading to benefits for individuals suffering from chronic nonspecific neck pain.Trial registrationBrazilian Registry of Clinical Trials - ReBEC RBR-7vbw5gd. Date of registration: August 06th, 2021.

Exploring pain mechanisms in hypermobile Ehlers-Danlos syndrome: A case-control study.

The hypermobile type of Ehlers-Danlos syndrome (hEDS) is a heritable connective tissue disorder, associated with joint hypermobility and prominent chronic pain. Because experimental pain testing in hEDS is scarce, the underlying mechanisms are still poorly understood. The present study assesses endogenous pain facilitation and pain inhibition in hEDS, using a protocol for temporal summation of pain (TSP), conditioned pain modulation (CPM) and exercise-induced hypoalgesia (EIH). Twenty women with hEDS and 20 age-matched healthy controls participated. After evaluating thermal and mechanical pain thresholds (PPT), TSP was assessed using 10 repetitive painful pressure stimuli. CPM was provoked using pressure as the test stimulus and hand immersion in hot water (46°) as the conditioning stimulus. EIH was assessed after a submaximal cycling protocol. The hEDS group demonstrated reduced PPTs and showed significantly more TSP after repeated painful stimuli than the control group. In comparison to the healthy control group, the hEDS group demonstrated significantly less EIH at the quadriceps test location. At the trapezius, EIH did not significantly differ between groups. No significant differences were found between the hEDS group and control group in the CPM response. The results demonstrate increased TSP in hEDS, suggesting increased central pain facilitation. EIH should be studied more extensively but may be disturbed when evaluated in the muscles that are activated during exercise. The CPM results are inconclusive and require more research. Studies regarding the mechanisms that underlie pain in hEDS are scarce, although it is the most prevalent and disabling symptom in this patient population. This study demonstrates increased temporal summation in hEDS and suggests that exercise-induced hypoalgesia may be reduced. Because exercise is a cornerstone in the multidisciplinary treatment of heritable connective tissue disorders, gaining knowledge in this field is important. Pressure stimuli were used to facilitate the international usability of the protocols, allowing for future data acquisition in large cohorts.

Sleep and Experimental Pain Sensitivity in People with HIV

People with HIV (PWH) appear to be at high risk for the experience of recurring pain symptoms throughout their lifetimes. There is also evidence to suggest a high prevalence of insomnia and sleep difficulties in PWH. Insomnia may lead to exaggerated pain states in PWH such as hyperalgesia, which refers to the phenomenon of heightened sensitivity to painful stimuli. The goals of this research are to examine differences in insomnia severity, sleep behaviors, and experimental pain sensitivity between PWH and controls without HIV. Participants included 25 PWH and 25 without HIV, who were all recruited from a local HIV treatment center (PWH) and the surrounding community (without HIV). Participants completed the Insomnia Severity Index and the RU_SATED scale, a measure of subjective sleep health. A quantitative sensory testing (QST) battery was then completed that included an assessment of pressure pain threshold (PPT) followed by temporal summation (TS) of mechanical pain; both administered at the trapezius. Compared to those without HIV, PWH reported greater severity of insomnia symptoms (p<.001) as well as poorer sleep health (p<.001). PWH also demonstrated significantly greater TS of mechanical pain compared to participants without HIV (p=.027). There was no significant difference for PPT (p=.901). In a stratified correlation analysis, the association between poorer sleep health and greater TS of mechanical pain was larger for PWH (r=-.344, p=.092) than it was for participants without HIV (r=-.004, p=.985). This ongoing study provides tentative evidence that PWH may experience worse sleep and enhanced pain facilitation (i.e., TS of mechanical pain) compared to those without HIV. It may also be that poor sleep is promoting enhanced pain facilitation in PWH; however, this possibility should be considered with caution given the small sample size and cross-sectional study design. Grant support from NHLBI - R01HL147603.

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

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). 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. 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). 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.

Preoperative Predictors of Complex Regional Pain Syndrome Outcomes in the 6 Months Following Total Knee Arthroplasty

This prospective observational study evaluated preoperative predictors of complex regional pain syndrome (CRPS) outcomes in the 6 months following total knee arthroplasty (TKA). Participants were n = 110 osteoarthritis patients (64.5% female) undergoing unilateral TKA with no prior CRPS history. Domains of negative affect (depression, anxiety, catastrophizing), pain (intensity, widespread pain, temporal summation of pain [TSP]), pain interference, sleep disturbance, and pro-inflammatory status (tumor necrosis factor-alpha [TNF-a]) were assessed preoperatively. CRPS outcomes at 6-week and 6-month follow-up included the continuous CRPS Severity Score (CSS) and dichotomous CRPS diagnoses (2012 IASP criteria). At 6 months, 12.7% of participants met CRPS criteria, exhibiting a “warm CRPS” phenotype. Six-week CSS scores were predicted by greater preoperative depression, anxiety, catastrophizing, TSP, pain intensity, sleep disturbance, and TNF-a (P’s < .05). Provisional CRPS diagnosis at 6 weeks was predicted by higher preoperative TSP, sleep disturbance, and TNF-a (P’s < .05). CSS scores at 6 months were predicted by more widespread and intense preoperative pain, and higher preoperative TSP, pain interference, and TNF-a (P’s < .01). CRPS diagnosis at 6 months was predicted only by more widespread and intense pain preoperatively (P’s < .05). Risk for CRPS following TKA appears to involve preoperative central sensitization and inflammatory mechanisms. Preoperative negative affect is unlikely to directly influence long-term CRPS risk. PerspectiveThis article identifies preoperative predictors of CRPS features at 6 months following total knee arthroplasty, including more widespread pain and higher pain intensity, temporal summation of pain, pain interference, and tumor necrosis factor-alpha levels. Findings suggest the importance of central sensitization and inflammatory mechanisms in CRPS risk following tissue trauma.

Evaluating the Relationship Between Acute Pain Perception and Gut Microbiota Among Female University Students in Japan: A Prospective Cohort Study.

The gut microbiota (GM) plays an important role in gut-brain communication, and the ‘gut-brain axis’ has attracted much attention as a factor influencing human host health. We previously reported that pain perception may be associated with GM composition in males. The aim of this study was to investigate the relationship between GM composition and pain perception among 42 healthy female university students in Japan. Pain perception was evaluated by pressure pain threshold (PPT), current perception threshold (CPT), temporal summation of pain (TSP), conditioned pain modulation (CPM), and a questionnaire on psychological state. CPT was stimulated at 5, 250, and 2,000 Hz, which reflected the thresholds of the C, Aδ, and Aβ fibers, respectively. Also, GM composition was estimated using 16S rRNA analysis. The lower alpha diversity was associated with, the lower PPT (rs = 0.330, P < 0.05) and CPT of 2000 Hz (re = 0.339, P < 0.05). Furthermore, alpha diversity was identified as an explanatory variable for PPT (β = 0.424, P < 0.01) and TSP (β = -0.317, P < 0.05), alpha diversity and state anxiety for CPT of 2000 Hz (β = 0.321, P < 0.05), and state anxiety for CPT of 250 Hz (β = 0.320, P < 0.05). However, there was no relationship between the rate of major phylum and pain perception.

Multimodal prediction of pain and functional outcomes 6 months following total knee replacement: a prospective cohort study

BackgroundKnee 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.MethodsThis 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.ResultsThe 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.ConclusionsThis 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.

Dynamic Functional Brain Connectivity Underlying Temporal Summation of Pain in Fibromyalgia.

Abnormal central pain processing is a leading cause of pain in fibromyalgia (FM) and is perceptually characterized with the psychophysical measure of temporal summation of pain (TSP). TSP is the perception of increasingly greater pain in response to repetitive or tonic noxious stimuli. Previous neuroimaging studies have used static (i.e., summary) measures to examine the functional magnetic resonance imaging (fMRI) correlates of TSP in FM. However, functional brain activity rapidly and dynamically reorganizes over time, and, similarly, TSP is a temporally evolving process. This study was undertaken to demonstrate how a complete understanding of the neural circuitry supporting TSP in FM thus requires a dynamic measure that evolves over time. We utilized novel methods for analyzing dynamic functional brain connectivity in patients with FM in order to examine how TSP-associated fluctuations are linked to the dynamic functional reconfiguration of the brain. In 84 FM patients and age- and sex-matched healthy controls, we collected high-temporal-resolution fMRI data during a resting state and during a state in which sustained cuff pressure pain was applied to the leg. FM patients experienced greater TSP than healthy controls (mean ± SD TSP score 17.93 ± 19.24 in FM patients versus 9.47 ± 14.06 in healthy controls; P = 0.028), but TSP scores varied substantially between patients. In the brain, the presence versus absence of TSP in patients with FM was marked by more sustained enmeshment between sensorimotor and salience networks during the pain period. Furthermore, dynamic enmeshment was noted solely in FM patients with high TSP, as interactions with all other brain networks were dampened during the pain period. This study elucidates the dynamic brain processes underlying facilitated central pain processing in FM. Our findings will enable future investigation of dynamic symptoms in FM.