Article
Immunology
Chunliang Xu, Maria Gulinello, Paul S. Frenette
Summary: Sensory nerves play a protective role in SCD, relieving the severity of VOE, and manipulating nociception may provide a promising approach for treating SCD.
JOURNAL OF EXPERIMENTAL MEDICINE
(2021)
Article
Biochemistry & Molecular Biology
Leah J. Elias, Isabella K. Succi, Melanie D. Schaffler, William Foster, Mark A. Gradwell, Manon Bohic, Akira Fushiki, Aman Upadhyay, Lindsay L. Ejoh, Ryan Schwark, Rachel Frazer, Brittany Bistis, Jessica E. Burke, Victoria Saltz, Jared E. Boyce, Anissa Jhumka, Rui M. Costa, Victoria E. Abraira, Ishmail Abdus-Saboor
Summary: By studying mice, it is found that sensory neurons labeled by Mrgprb4 are able to detect mechanical stimulation and play a crucial role in sexual receptivity and dopamine release. Optogenetic stimulation of these neurons can induce a conditioned place preference and a copulatory posture even in social isolation. In the absence of Mrgprb4-lineage neurons, female mice no longer find male mounts rewarding and show aggression instead.
Article
Immunology
Saskia Wedel, Praveen Mathoor, Oliver Rauh, Tim Heymann, Cosmin Ciotu, Dominik C. Fuhrmann, Michael J. M. Fischer, Andreas Weigert, Natasja de Bruin, Felix Hausch, Gerd Geisslinger, Marco Sisignano
Summary: This study demonstrates that the FKBP51 inhibitor SAFit2 ameliorates nerve injury-induced neuropathic pain by reducing neuroinflammation. SAFit2 reduces the infiltration of immune cells into neuronal tissue and counteracts the increased NF-kappa B pathway activation, leading to reduced cytokine and chemokine levels. Additionally, SAFit2 desensitizes the TRPV1 channel and reduces the release of pro-inflammatory neuropeptides.
JOURNAL OF NEUROINFLAMMATION
(2022)
Review
Behavioral Sciences
Deborah Chiabrando, Veronica Fiorito, Sara Petrillo, Francesca Bertino, Emanuela Tolosano
Summary: This study examines the relationship between heme and the pathophysiology of pain, highlighting the important regulatory role of heme in nociception and its association with pain-related diseases. However, the molecular mechanisms linking heme to pain pathways remain unclear at present.
NEUROSCIENCE AND BIOBEHAVIORAL REVIEWS
(2021)
Article
Biochemistry & Molecular Biology
Rebecca Chase, June Bryan de la Pena, Patrick R. Smith, Jennifer Lawson, Tzu-Fang Lou, Alexander D. Stanowick, Bryan J. Black, Zachary T. Campbell
Summary: Nociceptors are sensory neurons that play a crucial role in pain sensation. A recent study explored the potential of using sensory neurons derived from human induced pluripotent stem cells (hiPSCs) as a model for nociceptor research. The study compared the gene expression profiles of hiPSC-derived sensory neurons with mouse dorsal root ganglion (DRG) tissues and found similarities in key pain-related transcripts. Additionally, the study identified a translation factor called eIF5A as a potential target for inflammation-associated pain. Inhibition of eIF5A activity showed promising results in preventing pain hypersensitivity in vivo and reducing hiPSC activity in vitro.
Article
Neurosciences
Luke Grundy, Ashlee Caldwell, Sonia Garcia-Caraballo, David Grundy, Nick J. Spencer, Xinzhong Dong, Joel Castro, Andrea M. Harrington, Stuart M. Brierley
Summary: This study demonstrates the functional expression of MrgprA3 and MrgprC11 in bladder afferents for the first time. Activation of these receptors triggers hypersensitivity to distension, which is a critically valuable factor for therapeutic target development.
JOURNAL OF NEUROSCIENCE
(2021)
Article
Anesthesiology
Yan Liu, Yutong Liu, Nathachit Limjunyawong, Claire Narang, Hanna Jamaldeen, Shimeng Yu, Shivanie Patiram, Hong Nie, Michael J. Caterina, Xinzhong Dong, Lintao Qu
Summary: Chronic pruritus is a significant symptom of allergic contact dermatitis, but its underlying mechanisms are not well understood. TRPC3 is highly expressed in primary sensory neurons and is involved in peripheral sensitization. However, its role in acute and chronic itch is still unclear.
Article
Biotechnology & Applied Microbiology
Zongyou Guo, Chi-Kun Tong, Joanna Jackow, Yanne S. Doucet, Hasan E. Abaci, Wangyong Zeng, Corey Hansen, Ryota Hayashi, Dominick DeLorenzo, Avina Rami, Alberto Pappalardo, Ellen A. Lumpkin, Angela M. Christiano
Summary: Researchers have successfully differentiated itch sensory neuron-like cells from iPSC lines and innervated them into full thickness human skin constructs, providing new possibilities for the treatment and drug development of skin diseases such as atopic dermatitis.
BIOENGINEERING & TRANSLATIONAL MEDICINE
(2022)
Article
Biochemistry & Molecular Biology
Uma Anand, Praveen Anand, Mikael Hans Sodergren
Summary: Terpenes in Cannabis sativa inhibit capsaicin-induced calcium influx by activating Na+/K+ ATPase, which contributes to their analgesic effects.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2023)
Article
Neurosciences
Adrien Tassou, Maxime Thouaye, Damien Gilabert, Antoine Jouvenel, Jean-Philippe Leyris, Corinne Sonrier, Lucie Diouloufet, Ilana Mechaly, Sylvie Mallie, Juliette Bertin, Myriam Chentouf, Madeline Neiveyans, Martine Pugniere, Pierre Martineau, Bruno Robert, Xavier Capdevila, Jean Valmier, Cyril Rivat
Summary: Acute pain can lead to chronic pain, and the FLT3-tyrosine kinase receptor plays a crucial role in pain chronification after peripheral nerve injury. This study aimed to investigate whether injury-induced pain sensitization can also contribute to long-term mood disorders. The results showed that mice with double paw incisions exhibited an anxiodepressive-like phenotype and increased pain sensitivity compared to those with single incisions. These behavioral changes were associated with peripheral and spinal changes, including increased microglia activation. Blocking FLT3 and microglia activation alleviated the exaggerated pain sensitivity and anxiodepressive behaviors induced by double incisions. Humanized antibodies against FLT3 also reduced behavioral and microglia changes. Overall, this study suggests that peripheral lesions can not only cause exaggerated pain behaviors but also induce anxiodepressive disorders, and targeting peripheral FLT3 may provide a potential therapeutic approach.
PROGRESS IN NEUROBIOLOGY
(2023)
Review
Cell Biology
Wei-Dong Lai, Song Wang, Wen-Ting You, Si-Jia Chen, Jun-Jun Wen, Cun-Rui Yuan, Meng-Jia Zheng, Yan Jin, Jie Yu, Cheng-Ping Wen
Summary: Chronic pain is a disease characterized by long-lasting pain mediated by central and (or) peripheral sensitization. Patients with chronic pain exhibit heightened sensitivity to both harmful and non-harmful stimuli, making them less responsive to first-line analgesic treatment. Sinomenine, the main active ingredient in the plant sinomenium acutum, has been shown to have a powerful inhibitory effect on chronic pain. However, the underlying mechanism is still not fully understood. The immune system, along with inflammatory factors and neuropeptides, plays a crucial role in the pathogenesis of chronic pain. The interaction between the immune system and sensory neurons is essential for the development and maintenance of chronic pain. This review focuses on describing the potential analgesic effects of sinomenine by regulating the neuroimmune interaction.
FRONTIERS IN CELL AND DEVELOPMENTAL BIOLOGY
(2022)
Article
Geriatrics & Gerontology
Natalia L. dos Santos, Melissa E. Lenert, Zachary W. Castillo, Prapti H. Mody, Lucien T. Thompson, Michael D. Burton
Summary: Surgical procedures in older adults are increasing, but effective postoperative pain treatments are lacking. This study found that older males experienced delayed onset of hypersensitivity and faster resolution compared to younger counterparts. Age-related changes in neuronal function and inflammatory mechanisms contribute to postoperative pain development in older adults.
NEUROBIOLOGY OF AGING
(2023)
Article
Clinical Neurology
Carin A. Colebaugh, Jenna M. Wilson, K. Mikayla Flowers, Demario Overstreet, Dan Wang, Robert R. Edwards, Peter R. Chai, Kristin L. Schreiber
Summary: This study evaluated the differences in pain processing and situational pain catastrophizing between two music interventions (Unwind and favorite music) and a control condition (white noise). The results showed that participants had lower pain sensitivity, lower OA levels, and lower situational pain catastrophizing when listening to their favorite music. More research is needed to understand the mechanism by which music modulates pain processing.
Article
Developmental Biology
Antonella S. Rios, Ana Paula De Vincenti, Mailin Casadei, Jorge B. Aquino, Pablo R. Brumovsky, Gustavo Paratcha, Fernanda Ledda
Summary: The transcription factor Etv4 plays a crucial role in the development and function of peptidergic sensory neurons. It is regulated by NGF and is involved in the expression of genes associated with extracellular matrix remodeling. Etv4-null mice show reduced sensitivity to noxious stimuli and a decrease in the expression of the pain-transducing ion channel TRPV1.
Article
Neurosciences
Diego N. Messina, Emanuel D. Peralta, Cristian G. Acosta
Summary: The expression of the K2P channel TREK2 in neurons is regulated by GDNF, and this finding may have therapeutic potential in the treatment of chronic pain.
EXPERIMENTAL NEUROLOGY
(2022)
Article
Pharmacology & Pharmacy
Luca Eibach, Simone Scheffel, Madeleine Cardebring, Marie Lettau, M. Ozgur Celik, Andreas Morguet, Robert Roehle, Christoph Stein
Summary: The study investigated the effectiveness of cannabidivarin (CBDV) for treating HIV-associated neuropathic pain and found that it did not significantly reduce pain intensity. The results suggest that CBDV has no impact on the amount of pain medication used, pain characteristics, or quality of life.
CLINICAL PHARMACOLOGY & THERAPEUTICS
(2021)
Review
Pharmacology & Pharmacy
Partho Protim Adhikary, Zheng Tan, Brent D. G. Page, Sarah Hedtrich
Summary: Atopic diseases such as atopic dermatitis, allergic rhinitis, and allergic asthma are common allergic inflammatory diseases. Thymic stromal lymphopoietin (TSLP) plays a key role in regulating tissue microenvironment and driving atopic diseases.
PHARMACOLOGY & THERAPEUTICS
(2021)
Review
Biotechnology & Applied Microbiology
Qurrat Ul Ain, Estefania V. R. Campos, Ariel Huynh, Dominik Witzigmann, Sarah Hedtrich
Summary: Gene therapies are powerful in treating diseases, but face challenges in skin disorders due to the unique barrier properties of human skin that limit the efficient delivery of nucleic acid payloads. Delivery strategies are identified as the major obstacle in fully utilizing the potential of gene therapies for various human diseases, not just skin disorders.
TRENDS IN BIOTECHNOLOGY
(2021)
Article
Gastroenterology & Hepatology
Nestor Nivardo Jimenez-Vargas, Yang Yu, Dane D. Jensen, Diana Daeun Bok, Matthew Wisdom, Rocco Latorre, Cintya Lopez, Josue O. Jaramillo-Polanco, Claudius Degro, Mabel Guzman-Rodriguez, Quentin Tsang, Zachary Snow, Brian L. Schmidt, David E. Reed, Alan Edward Lomax, Kara Gross Margolis, Christoph Stein, Nigel W. Bunnett, Stephen J. Vanner
Summary: The fentanyl analogue NFEPP demonstrated effectiveness in inhibiting pain response in mice with colitis in an acidic environment, without causing respiratory depression, constipation, or hyperactivity. In contrast, fentanyl inhibited pain responses in both groups of mice and had side effects such as respiratory depression and hyperactivity.
Article
Biochemistry & Molecular Biology
Alexandra Gruber, Aaroh Anand Joshi, Patrick Graff, Jose Luis Cuellar-Camacho, Sarah Hedtrich, Daniel Klinger
Summary: Polymeric nanogels are potential nonirritating nanocarriers for topical delivery. Amphiphilic nanogels containing hydrophilic networks with hydrophobic domains can overcome the limitations of conventional hydrophilic networks, improving encapsulation of hydrophobic therapeutics and tailored interactions with the skin barrier.
Article
Engineering, Biomedical
Samuel Babity, Frederic Couture, Estefania V. R. Campos, Sarah Hedtrich, Raphael Hagen, Daniel Fehr, Mathias Bonmarin, Davide Brambilla
Summary: This study proposes a minimally invasive alternative strategy of delivering fluorescent ratiometric sensors to the skin using dissolving polymeric microneedles for real-time monitoring of physiological and pathological parameters. The sensors are capable of detecting reactive oxygen species, and are coupled with a custom-built, multiwavelength portable fluorescence detection system.
ADVANCED HEALTHCARE MATERIALS
(2022)
Article
Medicine, Research & Experimental
Patrick Graff, Stefan Honzke, Aaroh Anand Joshi, Guy Yealland, Emanuel Fleige, Michael Unbehauen, Monika Schafer-Korting, Andreas Hocke, Rainer Haag, Sarah Hedtrich
Summary: Human skin equivalents are useful tools in preclinical dermatological research. In this study, researchers investigated the suitability of inflammatory skin equivalents for testing the anti-inflammatory effects of dexamethasone. The results showed that topical application of dexamethasone reduced the expression of proinflammatory cytokines, increased the expression of skin barrier proteins, and facilitated the translocation of glucocorticoid receptors. The study also found that dexamethasone inhibited the gene expression of extracellular matrix components.
MOLECULAR PHARMACEUTICS
(2022)
Article
Microbiology
Jeanett Holzknecht, Sandrine Dubrac, Sarah Hedtrich, Laszlo Galgoczy, Florentine Marx
Summary: Candida albicans is a common opportunistic fungal pathogen in humans, causing superficial skin and mucosal infections as well as life-threatening systemic infections. To combat emerging drug resistance, there is an urgent need to identify new antifungal compounds with novel mechanisms of action. In this study, small cationic antifungal proteins from filamentous fungi show promise as next-generation antifungals for topical application, demonstrating efficacy against cutaneous C. albicans infection in a 3D skin model.
MICROBIOLOGY SPECTRUM
(2022)
Editorial Material
Medicine, Research & Experimental
Shyh-Dar Li, Ellen Wasan, Marcel Bally, Sarah Hedtrich
MOLECULAR PHARMACEUTICS
(2022)
Article
Multidisciplinary Sciences
Melih Oe Celik, Roger Negrete, Riccardo Di Rosso, Halina Machelska, Christoph Stein
Summary: Opioid agonist NFEPP can activate peripheral opioid receptors in injured tissue under acidic conditions, reducing side effects. By studying its interaction with the commonly used NSAID diclofenac, we found that diclofenac reduced inflammation-induced nociceptive responses and tissue acidosis, and had a moderate effect on the antinociceptive efficacy of NFEPP.
SCIENTIFIC REPORTS
(2022)
Article
Multidisciplinary Sciences
Arne Thies, Vikram Sunkara, Sourav Ray, Hanna Wulkow, M. Oezguer Celik, Fatih Yergoez, Christof Schuette, Christoph Stein, Marcus Weber, Stefanie Winkelmann
Summary: We have successfully designed, synthesized, and tested the prototype opioid painkiller NFEPP, which does not have adverse side effects. The design process was based on mathematical modeling of interactions between G-protein coupled receptors (GPCRs) and ligands, considering the different functions of GPCRs under pathological and healthy conditions. Additionally, we have proposed a novel stochastic model of GPCR function that takes into account intracellular dissociation of G-protein subunits and modulation of plasma membrane calcium channels, which depend on the parameters of inflamed and healthy tissue (pH, radicals). The model has been validated using in vitro experimental data for NFEPP and fentanyl at different pH values and radical concentrations.
SCIENTIFIC REPORTS
(2023)
Article
Anesthesiology
Claudius E. Degro, Nestor Nivardo Jimenez-Vargas, Quentin Tsang, Yang Yu, Mabel Guzman-Rodriguez, Elahe Alizadeh, David Hurlbut, David E. Reed, Alan E. Lomax, Christoph Stein, Nigel W. Bunnett, Stephen J. Vanner
Summary: This study found that repeated dosing of N-(3-fluoro-1-phenethylpiperidine-4-yl)-N-phenyl propionamide can provide safe and effective analgesia for colitis by targeting the acidified layers of the inflamed colon. The drug is able to inhibit human colonic nociceptors and has minimal side effects.
Article
Chemistry, Multidisciplinary
Juliana Bolsoni, Danny Liu, Fatemeh Mohabatpour, Ronja Ebner, Gaurav Sadhnani, Belal Tafech, Jerry Leung, Selina Shanta, Kevin An, Tessa Morin, Yihang Chen, Alfonso Arguello, Keith Choate, Eric Jan, Colin J. D. Ross, Davide Brambilla, Dominik Witzigmann, Jayesh Kulkarni, Pieter R. Cullis, Sarah Hedtrich
Summary: Despite advances in gene editing, delivering genetic tools to extrahepatic tissues, especially the skin, remains challenging. This study compared the efficacy of Cas9 mRNA and RNP-loaded LNPs for gene editing in the epidermal layers of human skin. The results showed that RNPs had a longer presence in slow-cycling epithelial cells. While Cas9 RNP and mRNA achieved similar gene editing rates, mRNA-loaded LNPs were more cytotoxic.
Review
Biotechnology & Applied Microbiology
Belal Tafech, Fatemeh Mohabatpour, Sarah Hedtrich
Summary: Gene therapies have the potential to effectively treat various diseases, but there are limitations in gene delivery. Surface modification of lipid nanoparticles can improve targeting efficacy for extrahepatic tissues.
JOURNAL OF GENE MEDICINE
(2023)
Article
Biochemical Research Methods
James J. Feng, Sarah Hedtrich
Summary: Organ-on-chip devices (OoCs) provide a more detailed understanding of (patho)physiological processes than traditional tissue models. However, the current design approach lacks systematic scaling, limiting the predictive value. The proposed similarity scaling approach can significantly improve the design and operation of OoCs.