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Catheter radiofrequency (RF) ablation for cardiac arrhythmias is a painful procedure. Prior work using functional near-infrared spectroscopy (fNIRS) in patients under general anesthesia has indicated that ablation results in activity in pain-related cortical regions, presumably due to inadequate blockade of afferent nociceptors originating within the cardiac system. Having an objective brain-based measure for nociception and analgesia may in the future allow for enhanced analgesic control during surgical procedures. Hence, the primary aim of this study is to demonstrate that the administration of remifentanil, an opioid widely used during surgery, can attenuate the fNIRS cortical responses to cardiac ablation.
Learn More >This prospective observational study evaluated preoperative predictors of CRPS outcomes 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 proinflammatory 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. PERSPECTIVE: : This 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.
Learn More >The current study used a dyadic analytic approach (actor-partner interdependence models) to assess the stability and interrelationships of intolerance of uncertainty (IU) among a cohort of youth with chronic pain and their parents (n = 156 dyads). Relationships between parent and youth IU, parent and youth pain interference, and parent and youth internalizing mental health symptoms were examined. At baseline and follow-up, youth and parents completed psychometrically-sound questionnaires to assess their respective IU, pain characteristics, and clinical outcomes (pain interference, anxiety, depressive, and posttraumatic stress symptoms). Our findings support the construct stability of IU over time, as well as intrapersonal (i.e., actor) effects of IU on follow-up youth pain interference and mental health symptoms and parents' mental health symptoms (but not parent pain interference). There were no interpersonal (i.e., partner) effects over time between youth and parent IU or between youth and parent IU and pain interference or mental health symptoms. These findings align with previous research evidencing IU as a transdiagnostic risk factor for a range of mental health concerns and extend previous findings by showing the stability of parent and youth IU over time and its potential predictive relevance to outcomes in a clinical sample of youth with chronic pain. Perspective: This article presents dyadic analyses assessing intrapersonal and interpersonal associations between intolerance of uncertainty (IU) and pain and mental health symptoms in youth with chronic pain and their parents. Analyses evidenced short-term construct stability of IU and intrapersonal (but not interpersonal) effects of IU on pain and mental health symptoms.
Learn More >In the lexical assessment of pain, an offshoot of the McGill Pain Questionnaire is the Pain Descriptor System (PDS) which assesses sensory, affective, and overall intensity of pain. To determine if sensory versus affective pain components might be selectively related to different aspects of disability, PDS scores were examined in relation to functional status and psychosocial impairment on the Pain Disability Questionnaire (PDQ). A sample of 629 chronic pain patients rated the degree to which each of 36 PDS words described their pain and also rated 15 items of the PDQ. Three regression models (including Group Lasso) were applied to the data. Results showed that as hypothesized, PDS sensory scores significantly predicted PDQ functional status, accounting for about 13% of the variance; PDS affective scores significantly predicted PDQ psychosocial impairment, accounting for 17% of the variance; PDS total scores significantly predicted PDQ total scores, accounting for approximately 24% of the variance. This supports the overall predictive validity of pain descriptors, while confirming more specific links between components of pain and facets of disability. Clinically, the patient's description of pain sensation may hold valuable clues to physical impairment, whereas the communication of affect/suffering is more likely to connote psychosocial difficulties in functioning. Perspective: Regression models (including Group Lasso) were applied to data on pain and disability from 629 patients. Findings support the Pain Descriptor System in assessing pain but further suggest that sensory descriptors are predictive of physical impairment from chronic pain, whereas affective descriptors are more predictive of psychologically-related disability.
Learn More >Pain chronicity is considered an important prognostic factor for outcome. Here, it was investigated whether pain duration influences outcome when only chronic patients (pain > three months) are considered. Secondary aims were to determine, in patients of any pain duration, how much variance in outcome is explained by pain duration and whether pain duration truly predicts outcomes, i.e. out-of-sample prediction in independent data.
Learn More >Sleep restriction alters cortical inhibition in migraine: A transcranial magnetic stimulation study.
Migraine is a primary headache disorder with a well-known association with insufficient sleep. However, both the underlying pathophysiology of the disease and the relationship with sleep is still unexplained. In this study, we apply transcranial magnetic stimulation to investigate possible mechanisms of insufficient sleep in migraine.
Learn More >To evaluate the efficacy and safety of intra-articular injection of diclofenac etalhyaluronate (DF-HA) in patients with osteoarthritis (OA) of the hip, ankle, shoulder, or elbow.
Learn More >Few studies have investigated factors associated with acute postsurgical pain (APSP) trajectories, and whether the APSP trajectory can predict chronic postsurgical pain (CPSP) remains unclear. We aimed to identify the predictors of APSP trajectories in patients undergoing gastrointestinal surgery. Moreover, we hypothesised that APSP trajectories were independently associated with CPSP. We conducted a prospective cohort study of 282 patients undergoing gastrointestinal surgery to describe APSP trajectories. Psychological questionnaires were administered 1 day before surgery. Meanwhile, demographic characteristics and perioperative data were collected. Average pain intensity during the first 7 days after surgery was assessed by a numeric rating scale (NRS). Persistent pain intensity was evaluated at 3 and 6 months postoperatively by phone call interview. CPSP was defined as pain at the incision site or surrounding areas of surgery with a pain NRS score ≥ 1 at rest. The intercept and slope were calculated by linear regression using the least squares method. The predictors for the APSP trajectory and CPSP were determined using multiple linear regression and multivariate logistic regression, respectively. Body mass index, morphine milligram equivalent (MME) consumption, preoperative chronic pain and anxiety were predictors of the APSP trajectory intercept. Moreover, MME consumption and preoperative anxiety could independently predict the APSP trajectory slope. The incidence of CPSP at 3 and 6 months was 30.58% and 16.42% respectively. APSP trajectory and age were predictors of CPSP 3 months postoperatively, while female sex and preoperative anxiety were predictive factors of CPSP 6 months postoperatively. Preoperative anxiety and postoperative analgesic consumption can predict APSP trajectory. In addition, pain trajectory was associated with CPSP. Clinicians need to stay alert for these predictors and pay close attention to pain resolution.
Learn More >An ACVR1 activating mutation causes neuropathic pain and sensory neuron hyperexcitability in humans.
Altered bone morphogenetic protein (BMP) signaling is associated with many musculoskeletal diseases. However, it remains unknown whether BMP dysfunction has direct contribution to debilitating pain reported in many of these disorders. Here we identified a novel neuropathic pain phenotype in patients with fibrodysplasia ossificans progressiva (FOP), a rare autosomal-dominant musculoskeletal disorder characterized by progressive heterotopic ossification. Ninety-seven percent of these patients carry an R206H gain-of-function point mutation in the bone morphogenetic protein (BMP) type I receptor ACVR1 (ACVR1R206H), which causes neofunction to Activin A and constitutively activates signaling through phosphorylated SMAD1/5/8. Although FOP patients can harbor pathological lesions in the peripheral and central nervous system, their etiology is unclear. Quantitative Sensory Testing (QST) of patients with FOP revealed significant heat and mechanical pain hypersensitivity. Although there was no major impact of ACVR1R206H on differentiation and maturation of nociceptive sensory neurons (iSNs) derived from FOP induced pluripotent stem cells (iPSCs), both intracellular and extracellular electrophysiology analysis of the ACVR1R206H iSNs displayed ACVR1-dependent hyperexcitability, a hallmark of neuropathic pain. Consistent with this phenotype, we recorded enhanced responses of ACVR1R206H iSNs to TRPV1 and TRPA1 agonists. Thus, activated ACVR1 signaling can modulate pain processing in humans and may represent a potential target for pain management in FOP and related BMP pathway diseases.
Learn More >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.
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