Gram-negative bacterial infections are accompanied by inflammation and somatic or visceral pain. These symptoms are generally attributed to sensitization of nociceptors by inflammatory mediators released by immune cells. Nociceptor sensitization during inflammation occurs through activation of the Toll-like receptor 4 (TLR4) signalling pathway by lipopolysaccharide (LPS), a toxic by-product of bacterial lysis. Here we show that LPS exerts fast, membrane delimited, excitatory actions via TRPA1, a transient receptor potential cation channel that is critical for transducing environmental irritant stimuli into nociceptor activity. Moreover, we find that pain and acute vascular reactions, including neurogenic inflammation (CGRP release) caused by LPS are primarily dependent on TRPA1 channel activation in nociceptive sensory neurons, and develop independently of TLR4 activation. The identification of TRPA1 as a molecular determinant of direct LPS effects on nociceptors offers new insights into the pathogenesis of pain and neurovascular responses during bacterial infections and opens novel avenues for their treatment.
Download full-text PDF |
Source |
|---|---|
| http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3905718 | PMC |
| http://dx.doi.org/10.1038/ncomms4125 | DOI Listing |
Publication Analysis
Top Keywords
Similar Publications
Navigating the Complexities of Anterior Cord Syndrome in a 71-Year-Old: A Case Study of Vertebral Osteomyelitis and Methicillin-Resistant Staphylococcus aureus Bacteremia.
Cureus
December 2024
Internal Medicine, Merit Health Wesley, Hattiesburg, USA.
Anterior cord syndrome is a rare yet critical neurological condition that poses significant challenges in clinical management. We present the case of a 71-year-old male with a medical history of hypertension, uncontrolled type II diabetes mellitus, hypothyroidism, and end-stage renal disease requiring dialysis who presented to the emergency department with complaints of chills, back pain, abdominal pain, and vomiting episodes. Based on the severity of the patient's illness, it was decided that inpatient admission would be best.
View Article and Find Full Text PDFEffects of radiotherapy on the hippocampus and hippocampal neurogenesis: a systematic review of preclinical studies.
Strahlenther Onkol
January 2025
Department of Radiation Medicine, Lenox Hill Hospital, Zucker School of Medicine at Hofstra/Northwell, New York, NY, USA.
Purpose: A comprehensive literature review was undertaken to understand the effects and underlying mechanisms of cranial radiotherapy (RT) on the hippocampus and hippocampal neurogenesis as well as to explore protective factors and treatments that might mitigate these effects in preclinical studies.
Methods: PubMed/MEDLINE, Web of Science, and Embase were queried for studies involving the effects of radiation on the hippocampus and hippocampal neurogenesis. Data extraction followed the Animal Research Reporting of In Vivo Experiments (ARRIVE) guidelines, and a risk of bias assessment was conducted for the included animal studies using the Systematic Review Centre for Laboratory Animal Experimentation (SYRCLE) risk of bias tool.
Frontal Fibrosing Alopecia Part II: Etiopathogenesis and Management.
J Am Acad Dermatol
January 2025
Dr. Phillip Frost Department of Dermatology and Cutaneous Surgery, University of Miami Miller School of Medicine, Miami, FL.
Frontal Fibrosing Alopecia (FFA) poses a distinct dermatological challenge with epithelial-mesenchymal transition (EMT) at its core, driving follicular cell transformation and fibrotic changes. Genetic studies highlight significant associations, while environmental triggers, such as implicated cosmetic products (sunblock, personal hair care products, and moisturizers), introduce complexity. Managing FFA proves daunting due to its chronic and unpredictable nature.
View Article and Find Full Text PDFNeurogenic inflammation and itch in barrier tissues.
Semin Immunol
January 2025
Center for Immunology and Inflammatory Diseases, Division of Rheumatology, Allergy & Immunology, Massachusetts General Hospital, Harvard Medical School, Boston, MA 02114, USA. Electronic address:
Once regarded as distinct systems, the nervous system and the immune system are now recognized for their complex interactions within the barrier tissues. The neuroimmune circuitry comprises a dual-network system that detects external and internal disturbances, providing critical information to tailor a context-specific response to various threats to tissue integrity, such as wounding or exposure to noxious and harmful stimuli like pathogens, toxins, or allergens. Using the skin as an example of a barrier tissue with the polarized sensory neuronal responses of itch and pain, we explore the molecular pathways driving neuronal activation and the effects of this activation on the immune response.
View Article and Find Full Text PDFLactoferrin Attenuates Pro-Inflammatory Response and Promotes the Conversion into Neuronal Lineages in the Astrocytes.
Int J Mol Sci
January 2025
Department of Biosciences, Biotechnologies and Environment, University of Bari, 70125 Bari, Italy.
Neurodegenerative diseases are characterized by progressive loss of neurons and persistent inflammation. Neurons are terminally differentiated cells, and lost neurons cannot be replaced since neurogenesis is restricted to only two neurogenic niches in the adult brain, whose neurogenic potential decreases with age. In this regard, the astrocytes reprogramming into neurons may represent a promising strategy for restoring the lost neurons and rebuilding neural circuits.
View Article and Find Full Text PDFWant AI Summaries of new PubMed Abstracts delivered to your In-box?
Enter search terms and have AI summaries delivered each week - change queries or unsubscribe any time!