RNAscope

Global Analyses of mRNA Expression in Human Sensory Neurons Reveals eIF5a as a Conserved Target for Inflammation-associated Pain

Sensory neurons derived from human induced pluripotent stem cells (hiPSCs) are a promising model. One limitation posed by the use of monocultures is the loss of cellular heterogeneity found in tissues. Here we make use of high-throughput RNA sequencing to quantify gene expression in hiPSC-derived mono-cultured and co-cultured sensory neurons.

Advanced Age and Sex Modulate Multiple Mu Opioid Receptor Signaling Mechanisms in the Rat Midbrain Periaqueductal Gray: Implications for Analgesia

Chronic pain is exceedingly prevalent in individuals over 65 years of age. Still, it is under-managed due in large part to a dearth of knowledge regarding the suitable dosing of opioids for chronic pain management. We have shown that advanced age and sex alter morphine modulation of persistent inflammatory pain (induced by intraplantar Complete Freund's adjuvant (CFA)). Specifically, morphine potency was highest in adult male rats (2mos), with a 2-fold rightward shift in the dose-response curve for aged males (18mos) and females regardless of age.

Different than Your Mother's Pain: Postsurgical Pain Modulation by Psychosocial Factors among Younger and Older Breast Cancer Patients

Younger age is a risk factor for worse outcomes following breast cancer surgery, including acute pain, development of persistent post-surgical pain, physical symptoms (arm disability), and greater psychological distress (depression). The biopsychosocial model of pain emphasizes the importance of considering the psychosocial context of pain experience, in addition to biological factors (age). Potentially, younger women's worse psychosocial adjustment after breast cancer surgery may explain their greater pain-related functional disability.

Brain-predicted Age Difference Mediates the Association between Self-reported Pain and PROMIS Sleep Impairment in Persons with Knee Osteoarthritis.

Knee osteoarthritis (KOA) is the most common cause of musculoskeletal pain (MSK), constituting a major public health burden. Sleep is among the multiple factors contributing to KOA-related pain, as sleep disturbance increases risk for worse pain-related outcomes in KOA. In addition, our lab found that brain cortical structure mediated the relationship between sleep qualities and pain severity in older adults with MSK.

Improving the Congruence between Knee Radiographs and Clinical/Experimental Pain: The Importance of Dispositional Traits

Knee osteoarthritis (OA) is a common progressive joint disease with increasing prevalence. There are inconsistent findings on the concordance between radiograph derived Kellgren-Lawrence (KL) scores and pain measures. We have previously reported that dispositional traits predict sensory sensitivity and psychosocial functioning. This study aims to determine whether consideration of a measure of dispositional trait, affect balance style (ABS), improves the congruence between KL scores and clinical and experimental pain.

Role of Cannabinoid CB2 Receptor in Alcohol Use Disorders: From Animal to Human Studies

Cumulative evidence has pointed out cannabinoid CB2 receptors (CB2r) as a potential therapeutic key target for treating alcohol use disorder (AUD). This review provides the most relevant results obtained from rodent and human studies, including an integrative section focused on the involvement of CB2r in the neurobiology of alcohol addiction. A literature search was conducted using the electronic databases Medline and Scopus for articles.

Molecular Basis of Bile Acid-FXR-FGF15/19 Signaling Axis

Bile acids (BAs) are a group of amphiphilic molecules consisting of a rigid steroid core attached to a hydroxyl group with a varying number, position, and orientation, and a hydrophilic side chain. While BAs act as detergents to solubilize lipophilic nutrients in the small intestine during digestion and absorption, they also act as hormones.

Loss of BMP2 and BMP4 Signaling in the Dental Epithelium Causes Defective Enamel Maturation and Aberrant Development of Ameloblasts

BMP signaling is crucial for differentiation of secretory ameloblasts, the cells that secrete enamel matrix. However, whether BMP signaling is required for differentiation of maturation-stage ameloblasts (MA), which are instrumental for enamel maturation into hard tissue, is hitherto unknown. To address this, we used an in vivo genetic approach which revealed that combined deactivation of the Bmp2 and Bmp4 genes in the murine dental epithelium causes development of dysmorphic and dysfunctional MA.

Orphan G-Protein Coupled Receptor GPRC5B Is Critical for Lymphatic Development

Numerous studies have focused on the molecular signaling pathways that govern the development and growth of lymphatics in the hopes of elucidating promising druggable targets. G protein-coupled receptors (GPCRs) are currently the largest family of membrane receptors targeted by FDA-approved drugs, but there remain many unexplored receptors, including orphan GPCRs with no known biological ligand or physiological function.

TGF-β as a Key Modulator of Astrocyte Reactivity: Disease Relevance and Therapeutic Implications

Astrocytes are essential for normal brain development and functioning. They respond to brain injury and disease through a process referred to as reactive astrogliosis, where the reactivity is highly heterogenous and context-dependent. Reactive astrocytes are active contributors to brain pathology and can exert beneficial, detrimental, or mixed effects following brain insults. Transforming growth factor-β (TGF-β) has been identified as one of the key factors regulating astrocyte reactivity.

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