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The enteric nervous system (ENS) coordinates diverse functions in the intestine but has eluded comprehensive molecular characterization because of the rarity and diversity of cells. Here we develop two methods to profile the ENS of adult mice and humans at single-cell resolution: RAISIN RNA-seq for profiling intact nuclei with ribosome-bound mRNA and MIRACL-seq for label-free enrichment of rare cell types by droplet-based profiling. The 1,187,535 nuclei in our mouse atlas include 5,068 neurons from the ileum and colon, revealing extraordinary neuron diversity. We highlight circadian expression changes in enteric neurons, show that disease-related genes are dysregulated with aging, and identify differences between the ileum and proximal/distal colon. In humans, we profile 436,202 nuclei, recovering 1,445 neurons, and identify conserved and species-specific transcriptional programs and putative neuro-epithelial, neuro-stromal, and neuro-immune interactions. The human ENS expresses risk genes for neuropathic, inflammatory, and extra-intestinal diseases, suggesting neuronal contributions to disease.
Learn More >Objectives Chronic postoperative pain is prevalent after robot-assisted laparoscopic hysterectomy for endometrial cancer. Preoperative Quantitative Sensory Testing (QST) has been utilized to identify patients at risk of developing chronic postoperative pain after a range of surgical procedures. The aim of this prospective, observational study was to (1) determine the prevalence of chronic postoperative pain, (2) assess selected preoperative risk factors for chronic postoperative pain, and (3) evaluate if preoperative QST profiling could predict the development of chronic postoperative pain following robot-assisted laparoscopic hysterectomy for endometrial cancer. Methods One-hundred and sixty consecutive patients were included and handheld pressure algometry, cuff pressure algometry, temporal summation of pain, conditioned pain modulation, and heat pain thresholds were assessed prior to surgery. Patients were asked to fill out a questionnaire concerning pain in the pre- and post-operative time period six months after surgery. Chronic postoperative pain was defined as persistent, moderate to severe pain (mean visual analogue scale (VAS)≥3) on a daily basis six months after surgery. Results The prevalence of chronic postoperative pain after robot-assisted laparoscopic hysterectomy for endometrial cancer was of 13.6% (95% CI 8.4-20.4%). Patients that would develop chronic postoperative pain had a lower BMI (p=0.032), a higher prevalence of preoperative pelvic pain (p<0.001), preoperative heat pain hyperalgesia (p=0.043) and a higher level of acute postoperative pain (p<0.001) when compared to patients that would not develop chronic postoperative pain. A logistic regression model demonstrated that the presence of preoperative pelvic pain was a significant, independent predictive risk factor for development of chronic postoperative pain (OR=6.62, 95% CI 2.26-19.44), whereas none of the QST parameters could predict postoperative pain. Conclusions Preoperative QST assessment could not predict the development of chronic postoperative pain despite preoperative heat pain hyperalgesia in patients that would develop chronic postoperative pain.
Learn More >Greater acceptance of chronic pain is associated with lesser levels of pain-related distress and disability and better overall functioning. Pain acceptance is most often assessed using the Chronic Pain Acceptance Questionnaire (CPAQ), which includes both an eight-item short form (CPAQ-8) and a twenty item parent measure (CPAQ-20). This study derived a two-item CPAQ for use in busy clinical settings and for repeated measurement during treatment, the CPAQ-2. An Item Response Theory approach was used to identify the strongest items from the CPAQ-20, one from each of its two subscales. Next, regression analyses were conducted to evaluate the utility of the CPAQ-2 by examining variance accounted for in the CPAQ-8, CPAQ-20, and in measures of depression, pain-related fear, physical disability, and psychosocial disability. Four clinical databases were combined (N = 1776) for the analyses. Items 9 and 14 were identified as the strongest CPAQ-20 items in the IRT analyses. The sum score of these two items accounted for over 60% of the variance in the CPAQ-8 and CPAQ-20. Furthermore, this score accounted for significant variance in measures of depression, pain-related fear, physical disability, and psychosocial disability after controlling for data collection method (i.e., in clinic or online), participant age, education, pain duration, and usual pain. Finally, the amount of variance accounted for by the CPAQ-2 was comparable to that accounted for by both the CPAQ-8 and CPAQ-20. These results provide initial support for the CPAQ-2 and suggest that it is well suited as a brief assessment of chronic pain acceptance.
Learn More >Retrospective longitudinal cohort.
Learn More >Classification of headache disorders is dependent on a subjective self-report from patients and its interpretation by physicians. We aimed to apply objective data-driven machine learning approaches to analyze patient-reported symptoms and test the feasibility of the automated classification of headache disorders. The self-report data of 2162 patients were analyzed. Headache disorders were merged into five major entities. The patients were divided into training (n = 1286) and test (n = 876) cohorts. We trained a stacked classifier model with four layers of XGBoost classifiers. The first layer classified between migraine and others, the second layer classified between tension-type headache (TTH) and others, and the third layer classified between trigeminal autonomic cephalalgia (TAC) and others, and the fourth layer classified between epicranial and thunderclap headaches. Each layer selected different features from the self-reports by using least absolute shrinkage and selection operator. In the test cohort, our stacked classifier obtained accuracy of 81%, sensitivity of 88%, 69%, 65%, 53%, and 51%, and specificity of 95%, 55%, 46%, 48%, and 51% for migraine, TTH, TAC, epicranial headache, and thunderclap headaches, respectively. We showed that a machine-learning based approach is applicable in analyzing patient-reported questionnaires. Our result could serve as a baseline for future studies in headache research.
Learn More >Migraine has consistently been connected with rosacea. Commonalities in epidemiology, trigger factors and associated neuropeptides support shared aetiology and pathophysiological pathways, though underlying mechanisms remain unclear. We established two cohorts of patients diagnosed with either migraine and/or rosacea. All patients were phenotyped in regard to migraine and rosacea. In this article, we describe the baseline parameters of the cohorts. In the future, we expect that these cohorts will help uncover potential disease overlaps and allow for prolonged follow-up through national Danish health registers.
Learn More >The Headache Disability Inventory assesses the dimensions of headache disability, but it is not available in Brazilian Portuguese yet. We aimed to translate the Headache Disability Inventory into Brazilian Portuguese and analyze its measurement properties.
Learn More >Breast cancer is the most frequent cancer in women. Chronic pain following mastectomy remains a significant problem. This study aimed to evaluate risk factors associated with postoperative chronic pain.
Learn More >Clinical heterogeneity is a peculiarity of vestibular migraine, in contrast to other vestibular disorders that have a more stereotypical expression. Migraine presents a range of variability in symptoms depending on the age of the patient. Supposing that migraine headache and vestibular migraine share the same pathogenetic mechanisms, a multiparametric analysis was performed to verify the hypotheses of an age-related influence on the clinical features of vestibular migraine at the onset.
Learn More >Cerebral proliferative angiopathy is a vascular malformation associated with compromised blood-brain barrier and with migraine-like headache. Treating blood-brain barrier-compromised patients with erenumab, an anti-calcitonin gene-related peptide receptor monoclonal antibody, may be risky.
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