Browse by Audience
Chronic pain is one of the most significant medical problems throughout the world. Recent evidence has confirmed the hippocampus as an active modulator of pain chronicity, but the underlying mechanisms remain unclear. Using in vivo electrophysiology, we identify a neural ensemble in the ventral hippocampal CA1 (vCA1) that shows inhibitory responses to noxious but not innocuous stimuli. Following peripheral inflammation, this ensemble becomes responsive to innocuous stimuli, representing hypersensitivity. Mimicking the inhibition of vCA1 neurons using chemogenetics induces chronic pain-like behaviors in naive mice, whereas activating vCA1 neurons in mice with peripheral inflammation results in a reduction of pain-related behaviors. Pathway-specific manipulation of vCA1 projections to basolateral amygdala (BLA) and infralimbic cortex (IL) shows that these pathways are differentially involved in pain modulation at different temporal stages of chronic inflammatory pain. These results confirm a crucial role of the vCA1 and its circuits in modulating the development of chronic pain.
Learn More >Surgery is often advised when conservative treatment fails in musculoskeletal pain conditions, but a substantial proportion still suffers chronic pain after surgery. Somatosensory processing system (SPS) signs were previously studied as potential predictors for chronic postsurgical pain, but results are inconsistent. Therefore, studying the evolution of SPS signs could be of added value. The aim was to summarize all studies that measured how SPS signs evolved after nociceptive targeted surgery in musculoskeletal disorders, and to find pre-, peri- and postoperative predictors for the evolution of these SPS signs. Data was summarized, and risk of bias and level of evidence and recommendation were determined. Twenty-one studies were included. Five scored a low, three a moderate, and 13 a high risk of bias. In general, no consistent evolution of SPS signs comparing pre- and postoperative values and predictors for this evolution in musculoskeletal disorders could be found. In most cases, static quantitative sensory testing (QST) did not change or conflicting results were found. On the other hand, dynamic QST mostly improved after surgery. Worthfully mentioning is that worsening of SPS signs was only seen at a follow-up of < 3 months after surgery, that conclusions are stronger when evaluating dynamic QST with a follow up of ≥ 3 months after surgery, and that pain improvement postsurgery was an important predictor. Future high quality research should focus on the evolution of SPS signs after nociceptive targeted surgery, accounting for pain improvement groups and focusing on pre, peri- and postoperative predictors of this evolution.
Learn More >Culturally diverse communities face barriers managing chronic musculoskeletal pain conditions including navigation challenges, sub-optimal healthcare provider engagement and difficulty adopting self-management behaviours.
Learn More >Quantitative sensory testing (QST) is increasingly used in pediatric chronic pain; however, assessment in youth with acute musculoskeletal (MSK) pain is limited. This study evaluated the feasibility, reliability, and sources of variability of a brief QST protocol in two clinical samples of youth with acute MSK pain. Participants were 277 youth (Mage=14.5 years, SD=2.0, range=11-18 years, 59% female, 83% non-Hispanic) across 3 geographic study sites who completed a QST protocol assessing pressure and thermal pain sensitivity, temporal summation of pain (TSP), and conditioned pain modulation (CPM) 8-weeks post MSK surgery (n=100) or within 4-weeks following an acute MSK injury (n=177). High feasibility was demonstrated by protocol completion rates ranging from 97.5%-100% for each task, with 95.3% of youth completing all tasks. Reliability was high, with reliability coefficients > 0.97 for 7 out of 8 QST parameters and minimal influence of examiner or participating site effects. Younger youth had lower pressure and heat pain thresholds (11-12 vs. 13-18 years, d=-0.80 to -0.56) and cold pain tolerance (d=-0.33). Hispanic youth had higher pressure and heat pain thresholds (d=0.37-0.45) and pain ratings for cold pain tolerance (d=0.54) compared to non-Hispanic youth. No significant differences were observed in QST values by sex or personal contextual factors at time of assessment (momentary pain, menstrual period, use of pain medications). Overall findings demonstrate feasibility of a brief QST protocol with youth with diverse acute MSK pain and data provide initial support for the reliability of this QST protocol for multisite research studies.
Learn More >With sweeping advances in precision delivery systems and manipulation of the genomes and transcriptomes of various cell types, medical biotechnology offers unprecedented selectivity for and control of a wide variety of biological processes, forging new opportunities for therapeutic interventions. This perspective summarizes state-of-the-art gene therapies enabled by recent innovations, with an emphasis on the expanding universe of molecular targets that govern the activity and function of primary sensory neurons and which might be exploited to effectively treat chronic pain.
Learn More >Migraine is a highly prevalent neurovascular disorder among reproductive-aged women. Whether migraine history and migraine phenotype might serve as clinically useful markers of obstetric risk is not clear. The primary objective of this study was to examine associations of pre-pregnancy migraine and migraine phenotype with risks of adverse pregnancy outcomes.
Learn More >Background Intralesional corticosteroid administration (ICA) is a first-line treatment for keloids. However, its clinical results are still highly variable and often suboptimal. Treatment results may strongly be influenced by various operator dependent factors. The aim of this study is to map the details of ICA in keloids described in randomized controlled trials (RCTs), hence presenting the scientific practice of a first-line treatment for keloids in the best available evidence. Summary A systematic search was performed on PubMed, Ovid MEDLINE, Ovid EMBASE and CENTRAL. Eligible studies were RCTs including patients with keloids treated with intralesional corticosteroids. Treatment and study design related data were charted on a predefined form. Thirty-eight RCTs were included for data extraction. Triamcinolone acetonide was used in 37 (97.4%) studies. Dosing per cm2 could only be compared among ten (26%) studies, and varied from 1 to 20 mg. The maximum dose per session varied from 20 to 80 mg. Anesthetics were administered locally and orally in seven and one RCT(s). Treatment intervals varied from weekly to monthly, with four weeks most frequently (50%) used. Needle size was reported in eleven (29%) studies and varied from 26 to 30-gauge. Syringe size was specified in four (11%) studies, being 1 mL. The injection level was described in eleven (29%) studies. Blanching as endpoint was reported in ten (26%) studies. Outcome measures varied widely, from height, surface area or volume, to Vancouver Scar Scale, Patient and Observer Scar Assessment Scale, pain and itch scores, patient satisfaction and different efficacy rates. Only six studies had a follow-up of ≥6 months. Recurrence was identified in two studies with 18 weeks and 1 year of follow-up. Adverse events were reported in 25 (66%) studies. Key messages There is incomplete reporting and substantial heterogeneity in many aspects of ICA and study design among RCTs. This scoping review underscores the urgent need for standardization of treatment protocol and study design to enhance and uniform research conduct among keloid studies.
Learn More >Endometriosis is a chronic gynecological condition that affects about 10% of women of reproductive age. Despite its prevalence, diagnosis is often delayed, misdiagnosis is common, and treatment options are poor. This study aimed at capturing ideas to improve endometriosis care from the patients' perspectives. We analyzed cross-sectional data from 1,000 adult patients in ComPaRe-Endometriosis (a French prospective e-cohort focused on endometriosis) who answered to the open-ended question: "If you had a magic wand, what would you change about your health care?". The free-text responses were analyzed by qualitative thematic analysis using an inductive approach. Patients had a mean age of 34.1 years (standard deviation = 8.1); 56% and 42% had stage IV disease or deep endometriosis, respectively. They elicited 2,487 ideas to improve the management of endometriosis, which were categorized into 61 areas of improvement, further grouped into 14 themes. The top five areas of improvement were mentioned by >10% of the patients and were to (1) train caregivers to develop their knowledge on the disease, (2) provide better management of daily pain and pain attacks, (3) take patient-reported symptoms seriously, (4) standardize diagnostic processes to improve early detection, and (5) have caregivers listen more to the patients. We identified 61 areas for improvement in endometriosis care. These results reflect patients' expectations in terms of management of their disease and will be useful to design a better global care for endometriosis from the patients' perspectives.
Learn More >Previous reports showed that LncRNA D26496 was downregulated and N6-methyladenosine (m6A) methyltransferase METTL3 was upregulated in sciatic nerve injury (SNI). YTH-Domain Family Member 2 (YTHDF2) regulated RNA degradation through recognizing m6A sites. However, whether METTL3-mediated m6A of D26496 plays a role in development of SNI is unknown. Therefore, in this study, we established a rat SNI model and a HO-induced Schwann cell injury model to investigate the role of D26496 in modulating SNI and how the expression of D26496 was regulated during this process. D26496 expression was downregulated in both models. Rats with SNI displayed severe oxidative stress, manifested as increased MDA production and decreased SOD and GSH activity. Moreover, overexpression of D26496 alleviated HO-induced Schwann cell injury likely by promoting cell proliferation and migration and suppressing cell apoptosis and oxidative stress. Mechanism studies found that METTL3 expression was upregulated after SNI, and silencing METTL3 reduced the D26496 m6A level, but upregulated D26496 expression. Subsequent studies found that YTHDF2 was upregulated after SNI, and abundant m6A modified D26496 in the precipitated protein-RNA complexes by anti-YTHDF2 antibody, whereas silencing YTHDF2 promoted D26496 expression but had no effect on m6A levels of D29496. Silencing D26496 reversed the protective effect of knocking down METTL3 or knocking down YTHDF2 on HO-induced cell damage. In vivo, D26496 overexpression alleviated SNI-induced neuropathic pain and oxidative stress. In conclusion, our results suggested that D26496 m6A modification mediated by METTL3 and recognition of D26496 m6A sites by YTHDF2 induced D26496 degradation, thereby participating in the progression of SNI.
Learn More >The aim of this NMA is to comprehensively analyze evidence of oral GnRH antagonist in the treatment of moderate-to-severe endometriosis-associated pain.
Learn More >