Previous PET studies in healthy humans have shown that brain μ-opioid receptor activation during experimental pain is associated with reductions in the sensory and affective ratings of the individual pain experience. The aim of this study was to find out whether brain μ-opioid receptor binding at the resting state, in absence of painful stimulation, can be a long-term predictor of experimental pain sensitivity. We measured μ-opioid receptor binding potential (BP(ND)) with μ-opioid receptor selective radiotracer [(11)C]carfentanil and positron emission tomography (PET) in 12 healthy male subjects. Later, we recruited these subjects to participate in a separate psychophysical testing session to measure cold pressor pain threshold, cold pressor pain tolerance and tactile sensitivity with von Frey monofilaments. We used both voxel-by-voxel and region-of-interest image analyses to examine the potential associations between μ-opioid receptor BP(ND) and psychophysical measures. The results show that striatal μ-opioid receptor BP(ND) predicts cold pressor pain threshold, but not cold pressor pain tolerance or tactile sensitivity. This finding suggests that striatal μ-opioid receptor density is involved in setting individual pain threshold.
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http://dx.doi.org/10.1016/j.neulet.2012.05.042 | DOI Listing |
JCI Insight
January 2025
Department of Biomedical Engineering, Oregon Health and Science University, Portland, United States of America.
Spatial profiling of tissues promises to elucidate tumor-microenvironment interactions and generate prognostic and predictive biomarkers. We analyzed single-cell, spatial data from three multiplex imaging technologies: cyclic immunofluorescence (CycIF) data we generated from 102 breast cancer patients with clinical follow-up, and publicly available imaging mass cytometry and multiplex ion-beam imaging datasets. Similar single-cell phenotyping results across imaging platforms enabled combined analysis of epithelial phenotypes to delineate prognostic subtypes among estrogen-receptor positive (ER+) patients.
View Article and Find Full Text PDFJ Clin Invest
January 2025
Laboratory of Translational Oncology and Translational Cancer Therapeutics, Warren Alpert Medical School of Brown University, Providence, United States of America.
Radiotherapy can be limited by pneumonitis which is impacted by innate immunity, including pathways regulated by TRAIL death receptor DR5. We investigated whether DR5 agonists could rescue mice from toxic effects of radiation and found two different agonists, parenteral PEGylated trimeric-TRAIL (TLY012) and oral TRAIL-Inducing Compound (TIC10/ONC201) could reduce pneumonitis, alveolar-wall thickness, and oxygen desaturation. Lung protection extended to late effects of radiation including less fibrosis at 22-weeks in TLY012-rescued survivors versus un-rescued surviving irradiated-mice.
View Article and Find Full Text PDFJ Clin Invest
January 2025
Department of Laboratory Medicine, Division of Translational Cancer Researc, Lund University Cancer Centre, Lund University, Lund, Sweden.
The biology centered around the TGF-beta type I receptor Activin Receptor-Like Kinase (ALK)1 (encoded by ACVRL1) has been almost exclusively based on its reported endothelial expression pattern since its first functional characterization more than two decades ago. Here, in efforts to better define the therapeutic context in which to use ALK1 inhibitors, we uncover a population of tumor-associated macrophages (TAMs) that, by virtue of their unanticipated Acvrl1 expression, are effector targets for adjuvant anti-angiogenic immunotherapy in mouse models of metastatic breast cancer. The combinatorial benefit depended on ALK1-mediated modulation of the differentiation potential of bone marrow-derived granulocyte-macrophage progenitors, the release of CD14+ monocytes into circulation, and their eventual extravasation.
View Article and Find Full Text PDFExpert Opin Pharmacother
January 2025
Department of Obstetrics and Gynecology, University of Florence, Careggi University Hospital, Florence, Italy.
Introduction: Dysmenorrhea is a painful symptom associated with uterine contractions and menstrual bleeding and is treated by administering analgesic drugs. Since progesterone receptors (PRs) have a major role in regulating uterine tissues (myometrium and endometrium) oral contraceptives are used off-label for treating primary or secondary dysmenorrhea. The development of selective progesterone receptor modulators (SPRMs) a class of synthetic steroids with agonistic, antagonistic, or mixed effects in targeting PRs in different tissues stimulated their possible clinical use for treating secondary dysmenorrhea related to uterine diseases (endometriosis, adenomyosis, uterine fibroids).
View Article and Find Full Text PDFPharmacol Rep
January 2025
Department of Translational Neuroscience, Center for Addiction Research, Wake Forest University School of Medicine, 115 South Chestnut St, Winston-Salem, NC, 27101, USA.
Background: Cocaine Use Disorder (CUD) remains a significant problem in the United States, with high rates of relapse and no present FDA-approved treatment. The acetylcholine neurotransmitter system, specifically through modulation of muscarinic acetylcholine receptor (mAChR) function, has shown promise as a therapeutic target for multiple aspects of CUD. Enhancement of the M mAChR subtype via positive allosteric modulation has been shown to inhibit the behavioral and neurochemical effects of cocaine across several rodent models of CUD.
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