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"Non-inflammatory" pain, pain that is not associated with measures of inflammation, is common in patients with inflammatory arthritis including rheumatoid arthritis (RA). One important cause of non-inflammatory pain is concomitant fibromyalgia. Systematic review has shown that fibromyalgia is common in inflammatory arthritis including RA affecting 1 in 5 patients and is associated with higher disease activity scores due to inflated tender joint count and patient global assessment. Consequently, many patients with RA and concomitant fibromyalgia may fail to reach treatment target and switch to alternate disease modifying drugs frequently. European Alliance of Association for Rheumatology has highlighted that concomitant fibromyalgia is an important consideration in assessing difficult-to-treat RA. The incidence and prevalence of fibromyalgia are higher in RA than the general population raising the possibility that fibromyalgia may be "secondary "to RA rather than a concomitant disease. The precise mechanisms whereby patients with RA develop fibromyalgia are unknown. In this review, we discussed fibromyalgia in RA, its clinical impact and epidemiology as well as data suggesting fibromyalgia might be "secondary". Lastly, we reviewed potential pathogenic mechanisms which included inflammatory cytokines sensitizing nociceptive neurones, temporal summation, also known as windup, from chronic pain and impaired coping from poor quality sleep and mental well-being. Deciphering the exact mechanisms may lead to treatment strategies that prevent development of secondary fibromyalgia and will address a common factor associated with difficult to treat RA.

Peripheral sensitization contributes to pathological pain. While prostaglandin E2 (PGE2) and nerve growth factor (NGF) sensitize peptidergic C-nociceptors (TRPV1+), glial cell line-derived neurotrophic factor (GDNF) sensitizes non-peptidergic C-neurons (IB4+). Sigma-1 receptor (σ1R) is a Ca -sensing chaperone known to modulate analgesia induced by opioid drugs. This receptor binds both to TRPV1 and the μ-opioid receptor (MOPr), although the functional repercussions of these physical interactions in peripheral sensitization are unknown.

Adolescents with recurrent pain miss out from school more often than pain-free peers. Research has so far used cross-sectional designs, focusing on non-specific absenteeism in clinical samples. Hence, it is unknown whether estimates of absenteeism are specifically linked to the pain itself or reflects the characteristics of clinical samples. This study aimed to prospectively explore pain-related school absenteeism in a non-clinical sample, its variance and potential risk factors.

Modern antiretroviral therapy (ART) has increased longevity of people with HIV (PWH) and shifted the age distribution of the HIV pandemic upward toward that of the general population. This positive development has also led to concerns about premature and/or accelerated neurocognitive and physical aging due to the combined effects of chronic HIV, accumulating comorbidities, adverse effects or possible toxicities of antiretroviral therapy (ART) and biological aging. Here we present results of comprehensive assessments over 12 years of 402 PWH in the CNS HIV ART Effects Research (CHARTER) program, who at follow-up were composed of younger (<60 years) and older (≥60 years) subgroups. Over the 12 years, ART use and viral suppression increased in both subgroups as did systemic and psychiatric comorbidities; participants in both subgroups also evidenced neurocognitive decline beyond what is expected in typical aging. Contrary to expectations, all these adverse effects were comparable in the younger and older CHARTER subgroups, and unrelated to chronological age. Neurocognitive decline was unrelated to HIV disease or treatment characteristics but was significantly predicted by the presence of comorbid conditions, specifically diabetes, hypertension, chronic pulmonary disease, frailty, neuropathic pain, depression, and lifetime history of cannabis use disorder. These results are not consistent with premature or accelerated neurocognitive aging due to HIV itself but suggest important indirect effects of multiple, potentially treatable comorbidities that are more common among PWH than in the general population. Good medical management of HIV disease did not prevent these adverse outcomes, and increased attention to a range of comorbid conditions in PWH may be warranted in their care.

TRPA1 channels have been implicated in mechanical and cold hypersensitivity in chronic pain. But how TRPA1 mediates this process is unclear. Here we show that IQ-motif containing GTPase activating protein 1 (IQGAP1) is responsible using a combination of biochemical, molecular, Ca2+ imaging and behavioural approaches. TRPA1 and IQGAP1 bind to each other and are highly colocalised in sensory DRG neurons in mice. The expression of IQGAP1 but not TRPA1 is increased in chronic inflammatory and neuropathic pain. However, TRPA1 undergoes increased trafficking to the membrane of DRG neurons catalysed by the small GTPase Cdc42 associated with IQGAP1, leading to functional sensitization of the channel. Activation of PKA is also sufficient to evoke TRPA1 trafficking and sensitization. All these responses are, however, completely prevented in the absence of IQGAP1. Concordantly, deletion of IQGAP1 markedly reduces mechanical and cold hypersensitivity in chronic inflammatory and neuropathic pain in mice. IQGAP1 thus promotes chronic pain by coupling the trafficking and signalling machineries to TRPA1 channels.

The incidence and prevalence of pediatric-onset inflammatory bowel disease (PIBD) are on the rise worldwide. Initial symptoms are often recognized with a delay, which reduces the quality of life and may lead to an increased rate of complications. The aim of this study was to determine the diagnostic delay in PIBD and to identify potential influencing factors. Therefore, data from the German-Austrian patient registry CEDATA-GPGE for children and adolescents with PIBD were analyzed for the period January 2014 to December 2018. There were 456 children identified in the data, thereof 258 children (57%) with Crohn's disease (CD) and 198 children (43%) with Ulcerative colitis (UC). The median age was 13.3 years (interquartile range (IQR) = 10.9-15.0), and 44% were females. The median diagnostic delay was 4.1 months (IQR = 2.1-7.0) in CD and 2.4 months (IQR = 1.2-5.1) in UC (p = 0.01). UC was associated with earlier diagnosis than CD (p < 0.001). Only a few factors influencing the diagnostic delay have been verified, e.g., abdominal pain at night and if video capsule endoscopy was performed. Diagnostic delay improved over the years in participating centers, but the level of awareness needs to be high even in common symptoms like abdominal pain.

Most patients with psoriatic arthritis begin with cutaneous psoriasis, which is why all early detection strategies are based on screening in the dermatological consultation and referral to a rheu matologist. However, there are cases of patients who consult initially for musculoskeletal symptoms, mostly joint pain, regardless of family and/or personal history of psoriasis. This study aimed to esti mate the frequency of psoriatic arthritis in a cohort of patients who consulted for polyarthralgia and to determine the differential features, at the time of clinical presentation, in relation to both patients with final diagnosis other than psoriatic arthritis and patients with diagnosis of rheumatoid arthritis.

Self-management (SM) is a key recommended strategy for managing chronic low back pain (CLBP). However, SM programmes generate small to moderate benefits for reducing pain and disability in patients with CLBP. The benefits of the SM programme can potentially be optimised by identifying specific subgroups of patients who are the best responders. To date, no longitudinal study has examined the predictive relationships between SM and biopsychosocial factors in patients with CLBP. The aim was to determine whether biopsychosocial factors predict SM and its change over time in patients with CLBP.

Mice are the most commonly used model animals for itch research and for development of anti-itch drugs. Most labs manually quantify mouse scratching behavior to assess itch intensity. This process is labor-intensive and limits large-scale genetic or drug screenings. In this study, we developed a new system, Scratch-AID Automatic Itch Detection), which could automatically identify and quantify mouse scratching behavior with high accuracy. Our system included a custom-designed videotaping box to ensure high-quality and replicable mouse behavior recording and a convolutional recurrent neural network (CRNN) trained with frame-labeled mouse scratching behavior videos, induced by nape injection of chloroquine (CQ). The best trained network achieved 97.6% recall and 96.9% precision on previously unseen test videos. Remarkably, Scratch-AID could reliably identify scratching behavior in other major mouse itch models, including the acute cheek model, the histaminergic model, and a chronic itch model. Moreover, our system detected significant differences in scratching behavior between control and mice treated with an anti-itch drug. Taken together, we have established a novel deep learning-based system that is ready to replace manual quantification for mouse scratching behavior in different itch models and for drug screening.

Neuroprognostication in severe traumatic brain injury (sTBI) is challenging and occurs in critical care settings to determine withdrawal of life sustaining therapies (WSLT). However, formal pediatric sTBI neuroprognostication guidelines are lacking, brain death criteria vary and dilemmas regarding WLST persist which lead to institutional differences. We studied WLST practice and outcome in pediatric sTBI to provide insight into WLST-associated factors and survivor recovery trajectory ≥ 1 year post-sTBI. This retrospective, single center observational study included patients < 18 years admitted to the Pediatric Intensive Care Unit (PICU) of Erasmus MC-Sophia (a tertiary university hospital) between 2012 and 2020 with sTBI defined as a Glasgow Coma Scale (GCS) ≤ 8 and requiring intracranial pressure (ICP) monitoring. Clinical, neuroimaging and electroencephalogram (EEG) data were reviewed. Multidisciplinary follow-up included the Pediatric Cerebral Performance Category (PCPC) score, educational level and commonly cited complaints. Seventy-eight children with sTBI were included (median age 10.5 years; IQR 5.0 – 14.1; 56% male; 67% traffic-related accidents). Median ICP monitoring was 5 days [IQR 3-8], 19 (24%) underwent decompressive craniectomy. PICU mortality was 21% (16/78): clinical brain death (cBD, 5/16), WLST due to poor neurological prognosis (WLST_neuro, 11/16). Significant differences (p < 0.001) between survivors and nonsurvivors: first GCS score, first pupillary reaction and first lactate, Injury Severity Score (ISS), pre-hospital cardiopulmonary resuscitation and Rotterdam CT score. WLST_neuro decision timing ranged from 0 to 31 days [median 2 days, IQR 0-5]. WLST_neuro decision (n=11) was based on neurologic examination (100%), brain imaging (100%) and refractory intracranial hypertension (5/11; 45%). WLST discussions were multidisciplinary with 100% agreement. Immediate agreement between medical team and caregivers was 81%. The majority (42/62, 68%) of survivors were poor outcome (PCPC score 3 to 5) at PICU discharge, of which 12 (19%) in a vegetative state. One year post-injury no patients were in a vegetative state and the median PCPC score had improved to 2 [IQR 2-3]. No patients died after PICU discharge. Twenty percent of survivors could not attend school two years post-injury. Survivors requiring an adjusted educational level increased to 45% within this timeframe. Chronic complaints were headache, behavioral and sleeping problems. In conclusion, two thirds of sTBI PICU mortality was secondary to WLST_neuro and occurred early post-injury. Median survivor PCPC score improved from 4 to 2 with no vegetative patients one year post-sTBI. Our findings show the WLST decision process was multidisciplinary and guided by specific clinical features at presentation, clinical course and (serial) neurological diagnostic modalities of which the testing combination was determined by case-to-case variation. This stresses the need for international guidelines to provide accurate neuroprognostication within an appropriate timeframe whereby overall survivor outcome data provides valuable context and guidance in the acute phase decision process.