Article
Biochemistry & Molecular Biology
Kaihua Zhang, David Julius, Yifan Cheng
Summary: This study utilized cryo-EM to visualize conformational transitions of TRPV1, revealing the dynamic transitions of its selectivity filter in response to algogenic agents. The findings also demonstrate a general framework for understanding how TRP channels function as polymodal signal integrators.
Article
Multidisciplinary Sciences
Heng Zhang, Jia-Jia Lin, Ya-Kai Xie, Xiu-Zu Song, Jia-Yi Sun, Bei-Lei Zhang, Yun-Kun Qi, Zhen-Zhong Xu, Fan Yang
Summary: The authors have engineered a peptide called s-RhTx as a positive allosteric modulator of the TRPV1 channel. It enhances the activity of TRPV1, allowing for reversible elimination of pain-sensing nerve terminals, providing long-lasting analgesia without affecting mice body temperature.
NATURE COMMUNICATIONS
(2023)
Article
Medicine, General & Internal
Weslania Nascimento, Noemi Tomsen, Saray Acedo, Cristina Campos-Alcantara, Christopher Cabib, Marta Alvarez-Larruy, Pere Clave
Summary: The study found that age and gender have an impact on spontaneous swallowing frequency in healthy individuals, with older age associated with lower spontaneous swallowing frequency. Gender did not have a significant effect on spontaneous swallowing frequency. Sensory stimulation with TRPV1 agonist capsaicin significantly increased spontaneous swallowing frequency in patients with post-stroke oropharyngeal dysphagia, suggesting a potential therapeutic strategy for central pattern generator activation in these patients.
Article
Neurosciences
Beiying Liu, Feng Qin
Summary: The study unveils the molecular basis underlying the high temperature dependence of the heat-sensitive TRPV2 channel, revealing a key molecular region in the proximal N-terminus that dictates the heat activation profile of the channel.
JOURNAL OF PHYSIOLOGY-LONDON
(2021)
Article
Multidisciplinary Sciences
Masayuki X. Mori, Ryo Okada, Reiko Sakaguchi, Hideharu Hase, Yuko Imai, Onur K. Polat, Satoru G. Itoh, Hisashi Okumura, Yasuo Mori, Yasushi Okamura, Ryuji Inoue
Summary: This study identified the crucial positions for PIP2 binding in TRPC6 channels through mutagenesis screening, and found that Arg437 and Lys442 in the pre-S1 domain/shoulder play a crucial role in interacting with PIP2. Computer simulations provided structural insights, showing that basic residues in the pre-S1 domain/shoulder are key regulators for PIP2-dependent gating.
SCIENTIFIC REPORTS
(2022)
Article
Biochemistry & Molecular Biology
Yin-Zi Ye, Hao Zhang, Jiameng Li, Ren Lai, Shilong Yang, Wei-Guo Du
Summary: Temperature sensing is crucial for living organisms' survival, and turtle embryos exhibit thermotaxic behavior by activating two heat-sensitive ion channels, MrTRPA1 and MrTRPV1. These TRP channels play a key role in controlling the thermal behavior of turtle embryos through a delicate functional balance.
Review
Physiology
Tamara Rosenbaum, Leon D. Islas
Summary: The ability to detect environmental stimuli is crucial for survival, and ion channels, such as TRP proteins, play a key role in this process. The TRPV subfamily, which belongs to the TRP family, responds to various chemical and physical changes. Despite intensive research in the past two decades, controversies still exist regarding the function of these proteins due to their complexity. In this article, we discuss important features of their regulation and highlight efforts to advance the field.
ANNUAL REVIEW OF PHYSIOLOGY
(2023)
Article
Physiology
Elisabeth Jubileum, Uta Binzen, Rolf-Detlef Treede, Wolfgang Greffrath
Summary: In this study, we investigated the transduction mechanisms for noxious laser heat pulses in native sensory neurons at milliseconds temporal and subcellular spatial resolution. We characterized strength-duration properties, intensity coding, and spatial summation within single neurons. Thermal excitation of parts of a nociceptor spread via both membrane depolarization and intracellular calcium diffusion.
PFLUGERS ARCHIV-EUROPEAN JOURNAL OF PHYSIOLOGY
(2022)
Article
Pharmacology & Pharmacy
Fang Hu, Xu Cao, Canyang Niu, KeWei Wang
Summary: The coassembly of TRPV3 and TRPV4 channels into heterotetrameric complexes increases the functional diversity within the channel subfamily and may play a role in fine-tuning environmental detection and temperature sensation in mammals.
MOLECULAR PHARMACOLOGY
(2022)
Review
Neurosciences
Tamara Rosenbaum, Sara L. Morales-Lazaro, Leon D. Islas
Summary: Recent studies on transient receptor potential (TRP) channel structure have provided valuable insights into their role in normal sensations and pain. This review article examines the recent advances in understanding the relationship between the structure and function of TRP ion channels and their involvement in pain. The perception of nociceptive signals and the avoidance of pain are crucial for survival. TRP channels, as transducers of harmful signals, play a significant role in detecting and translating these signals into pain. Cryogenic electron microscopy has allowed researchers to explore the molecular details of TRP channels, complementing functional studies and enhancing our understanding of their contribution to pain generation and maintenance.
NATURE REVIEWS NEUROSCIENCE
(2022)
Article
Cell Biology
Aida Aghazadeh, Mohammad Ali Hosseinpour Feizi, Leila Mehdizadeh Fanid, Mohammad Ghanbari, Leila Roshangar
Summary: Heat stress increases core body temperature, leading to the release of free radicals and neuronal damage in the central nervous system. TRPV1 and TRPV4 channels play essential roles in this process as thermosensors. Results demonstrate a significant upregulation of TRPV1 expression, while TRPV4 expression decreases in a time-dependent manner in heat-stressed mice, along with alterations in oxidative markers.
CELLULAR AND MOLECULAR NEUROBIOLOGY
(2021)
Article
Chemistry, Multidisciplinary
Anny Treat, Vianie Henri, Junke Liu, Joyce Shen, Mauricio Gil-Silva, Alejandro Morales, Avaneesh Rade, Kevin Joseph Tidgewell, Benedict Kolber, Young Shen
Summary: Capsaicin, a compound found in hot chili peppers, is a known analgesic but its high pungency limits its application. To address this issue, novel capsaicin analogues were developed with reduced pungency. These analogues have been shown to alleviate pain behavior and reduce thermal sensitivity.
Article
Multidisciplinary Sciences
Yuta Masuda, Riho Sakai, Issei Kato, Kei Nagashima
Summary: This study assessed the heat-escape/cold-seeking behavior during thermoregulation in mice and the influence of TRPV1 channels. The findings suggest that capsaicin-induced desensitization of TRPV1 channels suppresses heat-escape/cold-seeking behavior in mice during heat exposure, resulting in hyperthermia.
Article
Pharmacology & Pharmacy
Roger L. Papke, Marta Quadri, Alican Gulsevin
Summary: We discuss models for the activation and desensitization of alpha 7 nicotinic acetylcholine receptors (nAChRs), as well as the effects of type II positive allosteric modulators (PAMs) that destabilize alpha 7 desensitized states. The cholinergic anti-inflammatory system (CAS) modulates inflammation and pain through alpha 7 nAChRs in cells of the immune system. Silent agonists and type II PAMs play important roles in CAS regulation.
PHARMACOLOGICAL RESEARCH
(2023)
Review
Biochemistry & Molecular Biology
Felix Yang, Andy Sivils, Victoria Cegielski, Som Singh, Xiang-Ping Chu
Summary: Pharmacomodulation of membrane channels is a crucial field in understanding physiological conditions and diseases. Transient receptor potential (TRP) channels, especially TRPM, TRPV, and TRPC, have been shown to mediate pain sensation, neuropsychiatric disorders, and epilepsy, providing potential therapeutic targets. This review emphasizes the importance of these TRP channels and their potential for future clinical treatments, giving patients hope for improved care.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2023)
Article
Biochemistry & Molecular Biology
Anna K. Becker, Andrea Auditore, Monika Pischetsrieder, Karl Messlinger, Thomas Fleming, Peter W. Reeh, Susanne K. Sauer
JOURNAL OF BIOLOGICAL CHEMISTRY
(2020)
Letter
Cell Biology
Lisa A. Gebhardt, Tetyana I. Kichko, Michael J. M. Fischer, Peter W. Reeh
JOURNAL OF CELL BIOLOGY
(2020)
Article
Anesthesiology
Alexandru Babes, Tatjana I. Kichko, Tudor Selescu, Alexandra Manolache, Cristian Neacsu, Lisa Gebhardt, Peter W. Reeh
Summary: This study investigated the adverse effects of PUVA therapy and found that TRPA1 and TRPV1 channels play important roles in the activation and photosensitization of peripheral nociceptors. The results suggest a possible therapeutic approach to alleviate the adverse effects associated with PUVA therapy.
EUROPEAN JOURNAL OF PAIN
(2021)
Article
Medicine, Research & Experimental
M. Khalil, Z. Zhang, H. Abdel-Aziz, S. Rabini, R. M. Ammar, P. W. Reeh, M. A. Engel
Article
Medicine, Research & Experimental
Z. Zhang, M. A. Engel, E. Koch, P. W. Reeh, M. Khalil
Summary: The herbal combination Menthacarin has been shown to induce calcium influx in sensory neurons, macrophages, and colonic organoids, potentially contributing to its clinical desensitizing effects in patients with FGIDs. Additionally, repeated applications of Menthacarin lead to desensitization of calcium responses in sensory neurons and colonic organoids.
Article
Anesthesiology
Miriam M. Duell, Martina Stengel, Vivien Ries, Marion Strupf, Peter W. Reeh, Andreas E. Kremer, Barbara Namer
Summary: LPA can cause pain and itch in humans depending on the mode of application and activates afferent human C fibers.
Article
Neurosciences
Tal Hoffmann, Katrin Kistner, Sonja L. J. Joksimovic, Slobodan M. Todorovic, Peter W. Reeh, Susanne K. Sauer
Summary: The study evaluated the role of the Ca(V)3.2 T-type calcium channel in painful diabetic neuropathy induced by hyperglycemia, showing significant changes in peripheral C-fiber functions.
EXPERIMENTAL NEUROLOGY
(2021)
Review
Physiology
Peter W. Reeh, Michael J. M. Fischer
Summary: This article reviews the discoveries of the Nobel laureates David Julius and Ardem Patapoutian in the field of temperature and touch receptors, TRPV1 and PIEZO1/2, and discusses topics such as mechanosensitivity and mechanical hyperalgesia.
PFLUGERS ARCHIV-EUROPEAN JOURNAL OF PHYSIOLOGY
(2022)
Correction
Physiology
Peter W. Reeh, Michael J. M. Fischer
PFLUGERS ARCHIV-EUROPEAN JOURNAL OF PHYSIOLOGY
(2022)
Article
Multidisciplinary Sciences
Isabel Wank, Lisa Kutsche, Silke Kreitz, Peter Reeh, Andreas Hess
Summary: RTX desensitization of TRPV1-signaling disrupts thermal nociception and affects two distinct brain subnetworks, leading to reduced central nervous system responses to high temperatures in male rats. Resting state and graph-theoretical network analyses provide detailed insight into cerebral processing of noxious temperatures.
Article
Physiology
Tal Hoffmann, Florian Klemm, Tatjana Kichko, Susanne K. Sauer, Katrin Kistner, Bernhard Riedl, Patrick Raboisson, Lei Luo, Alexandru Babes, Laurence Kocher, Giancarlo Carli, Michael J. M. Fischer, Peter W. Reeh
Summary: The formalin test, widely used to screen antinociceptive drug candidates, may not accurately target inflammatory pain. Formaldehyde can stimulate nerve fibers and induce pain-related behaviors. TRPA1 is identified as the primary transducer of formaldehyde effects on sensory neurons, but the actions of formaldehyde require further discussion and research.
PHYSIOLOGICAL REPORTS
(2022)
Article
Clinical Neurology
Anna K. Becker, Alexandru Babes, Miriam M. Duell, Mohammad Khalil, Zoltan Kender, Jan Groener, Barbara Namer, Peter W. Reeh, Susanne K. Sauer
Summary: This study investigates the contribution of MGO to the development of pain and hyperalgesia in diabetic neuropathy. It found that TRPA1-expressing C-nociceptors play a crucial role in the development of spontaneous activity and sensitization in response to MGO.
JOURNAL OF THE PERIPHERAL NERVOUS SYSTEM
(2023)
Article
Medicine, Research & Experimental
Monika Hollenhorst, Rajender Nandigama, Saskia B. Evers, Igor Gamayun, Noran Abdel Wadood, Alaa Salah, Mario Pieper, Amanda Wyatt, Alexey Stukalov, Anna Gebhardt, Wiebke Nadolni, Wera Burow, Christian Herr, Christoph Beisswenger, Soumya Kusumakshi, Fabien Ectors, Tatjana Kichko, Lisa Huebner, Peter Reeh, Antje Munder, Sandra-Maria Wienhold, Martin Witzenrath, Robert Bals, Veit Flockerzi, Thomas Gudermann, Markus Bischoff, Peter Lipp, Susanna Zierler, Vladimir Chubanov, Andreas Pichlmair, Peter Koenig, Ulrich Boehm, Gabriela Krasteva-Christ
Summary: This study reveals that tracheal brush cells express functional taste receptors and that bitter taste signaling induces neurogenic inflammation, which mediates secretion of immune mediators and defense against bacterial infections.
JOURNAL OF CLINICAL INVESTIGATION
(2022)
Review
Substance Abuse
Lars Arendt-Nielsen, Earl Carstens, Gordon Proctor, Yves Boucher, Pere Clave, Kent Albin Nielsen, Thomas A. Nielsen, Peter W. Reeh
Summary: Nicotine provokes irritation, burning and pain in the oral cavity and throat. Managing these side effects will ensure better compliance to oral NRT products and hence increase the success of smoking cessation. A specific class of sensory receptors (TRP channels) are involved in mediating nicotine's sensory side effects, making them potential treatment targets. Many natural compounds are potentially beneficial modulators of TRP channels.
NICOTINE & TOBACCO RESEARCH
(2022)
Article
Physiology
Kristina Rodionova, Roland Veelken, Karl F. Hilgers, Eva-Maria Paulus, Peter Linz, Michael J. M. Fischer, Martina Schenker, Peter Reeh, Gisa Tiegs, Christian Ott, Roland Schmieder, Mario Schiffer, Kerstin Amann, Tilmann Ditting
AMERICAN JOURNAL OF PHYSIOLOGY-RENAL PHYSIOLOGY
(2020)