Article
Biochemistry & Molecular Biology
Yingying Nie, Yanxin Li, Lei Liu, Shouyan Ren, Yuhua Tian, Fan Yang
Summary: The study revealed that a series of polyols can significantly elevate the heat activation threshold temperature of TRPV1, suggesting a potential role in reducing heat-induced pain sensation. The modulatory effects of these polyols are observed only when perfused extracellularly, emphasizing the importance of the extracellular regions of TRPV1 for heat activation modulation.
JOURNAL OF BIOLOGICAL CHEMISTRY
(2021)
Article
Cell Biology
Yongxue Zhang, Qi Miao, Sai Shi, Han Hao, Xinmeng Li, Zeyao Pu, Yakun Yang, Hailong An, Wei Zhang, Youzhen Kong, Xu Pang, Cunyang Gu, Nikita Gamper, Yi Wu, Hailin Zhang, Xiaona Du
Summary: Protein disulfide isomerase (PDI) plays a key role in maintaining cellular homeostasis by mediating protein folding and it can be a potential therapeutic target for chronic pain. The expression and secretion of PDI from primary sensory neurons is upregulated in inflammatory and neuropathic pain models. Deletion of PDI in nociceptive DRG neurons reduces inflammatory and neuropathic heat hyperalgesia. Secreted PDI activates TRPV1 channels through oxidative modification, indicating that PDI acts as an unconventional positive modulator of TRPV1.
Review
Biochemistry & Molecular Biology
Marina Ramal-Sanchez, Nicola Bernabo, Luca Valbonetti, Costanza Cimini, Angela Taraschi, Giulia Capacchietti, Juliana Machado-Simoes, Barbara Barboni
Summary: TRPV1, a polymodal sensor, is extensively studied and plays important roles in various key events in post-ejaculatory life of sperm. This review gathers all the known modulators of TRPV1 function and their relationship with reproductive processes, providing insights into the indirect participation of TRPV1 receptor during sperm migration events such as chemotaxis, thermotaxis, and rheotaxis. Additionally, TRPV1 is highlighted as a potential pharmacological target in male reproductive system-related pathologies.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2021)
Article
Biology
Julian Alexander Schreiber, Anastasia Derksen, Gunnar Goerges, Sven Schuette, Jasmin Soergel, Aytug K. Kiper, Nathalie Strutz-Seebohm, Tobias Ruck, Sven G. Meuth, Niels Decher, Guiscard Seebohm
Summary: It is reported that the drug cloxyquin activates the TWIK-related spinal cord K+ channel (TRESK) by stabilizing the inner selectivity filter. This finding has significant implications for future drug development.
COMMUNICATIONS BIOLOGY
(2023)
Article
Pharmacology & Pharmacy
Jan Daniluk, Thomas Voets
Summary: TRPV1 antagonists have pH-dependent effects on channel inhibition, but their modality selectivity is not strict. The antagonistic efficacy of TRPV1 antagonists is limited at acidic pH, which may restrict their analgesic efficacy in injured tissues.
BRITISH JOURNAL OF PHARMACOLOGY
(2023)
Article
Pharmacology & Pharmacy
Mayo Tamada, Yoshiaki Ohi, Daisuke Kodama, Ken Miyazawa, Shigemi Goto, Akira Haji
Summary: The present study demonstrates that chronic orofacial pain in the PNL model is a result of facilitation of spontaneous excitatory synaptic transmission in the Vc region through TRPV1.
EUROPEAN JOURNAL OF PHARMACOLOGY
(2021)
Article
Biophysics
Taylor M. Mott, Jordan S. Ibarra, Nivitha Kandula, Eric N. Senning
Summary: Protein structures and mutagenesis studies have played a crucial role in understanding the function of ion channels, but selecting the right residues for mutagenesis can be challenging. This study explored the use of human population genomic data to guide the selection of mutagenesis sites in TRPV1. By analyzing the data from gnomAD 2.1.1, the researchers found that certain residues involved in interactions between subunits or domains of the channel had a reduced number of variants. Further investigations revealed the important roles of these residues in TRPV1 function.
BIOPHYSICAL JOURNAL
(2023)
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
Neurosciences
Ludivine Pidoux, Kevin Delanoe, Julie Barbier, Fabien Marchand, Eric Lingueglia, Emmanuel Deval
Summary: LPC, a member of the phospholipid family, plays an important role in pain modulation by regulating various pain-related ion channels, such as ASIC3, which is significant for understanding chronic pain conditions.
FRONTIERS IN MOLECULAR NEUROSCIENCE
(2022)
Article
Cell Biology
Zhongyang Lv, Xingquan Xu, Ziying Sun, Yannick Xiaofan Yang, Hu Guo, Jiawei Li, Kuoyang Sun, Rui Wu, Jia Xu, Qing Jiang, Shiro Ikegawa, Dongquan Shi
Summary: The study demonstrates that TRPV1 inhibits M1 macrophage polarization in synovium, thereby reducing synovitis and attenuating the progression of osteoarthritis.
CELL DEATH & DISEASE
(2021)
Article
Pharmacology & Pharmacy
Masakazu Kotoda, Toru Matsuoka, Keiichi Wada, Selwyn Jayakar, Hirofumi Ino, Koji Kawago, Yasutomo Kumakura
Summary: This study investigated the potential of amiodarone, a multiple channel blocker, as a long-lasting local anesthetic and analgesic. It was found that amiodarone produced robust anesthesia and the co-administration of TRPV1 agonist capsaicin prolonged the duration of sensory blockade without affecting motor blockade. Low-dose amiodarone was also effective in relieving inflammatory pain without the need for capsaicin co-administration. Furthermore, local amiodarone did not cause any cardiovascular or central nervous system side effects.
FRONTIERS IN PHARMACOLOGY
(2022)
Article
Chemistry, Medicinal
Johan L. A. Nilsson, Christophe Mallet, Kiseko Shionoya, Anders Blomgren, Anders P. Sundin, Lars Grundemar, Ludivine Boudieu, Anders Blomqvist, Alain Eschalier, Ulf J. Nilsson, Peter M. Zygmunt
Summary: Research suggests that analgesics and antipyretics without liver toxicity can be derived from paracetamol, showing potential for future applications. Paracetamol exhibits separate mechanisms for producing antipyretic and analgesic effects, which may lead to better therapeutic benefits for various conditions.
EUROPEAN JOURNAL OF MEDICINAL CHEMISTRY
(2021)
Article
Biochemistry & Molecular Biology
Alessio Lissoni, Siyu Tao, Rosalie Allewaert, Katja Witschas, Luc Leybaert
Summary: Cx43 hemichannels (HCs) and Panx1 channels, two genetically distant protein families, have been debated for their similarities in expression, membrane topology, and electrical properties. This study used mimetic peptides Gap19 and (10)Panx1 to investigate their cross-effects on Cx43 HCs and Panx1 channels. The results showed that Gap19 significantly inhibited Panx1 channels, while high concentrations of (10)Panx1 significantly reduced the activity of Cx43 HCs.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2023)
Article
Neurosciences
Kihwan Lee, Young In Choi, Sang-Taek Im, Sung-Min Hwang, Han-Kyu Lee, Jay-Zoon Im, Yong Ho Kim, Sung Jun Jung, Chul-Kyu Park
Summary: Riboflavin, also known as vitamin B-2, can be found in foods and used as a dietary supplement. Research indicates that riboflavin inhibits histamine-dependent itch by modulating TRPV1 activity, suggesting it may be a useful drug for treating this type of itch.
FRONTIERS IN MOLECULAR NEUROSCIENCE
(2021)
Article
Biochemistry & Molecular Biology
Nannan Su, Wenxuan Zhen, Heng Zhang, Lingyi Xu, Yitian Jin, Xiaoying Chen, Cheng Zhao, Qinrui Wang, Xinyan Wang, Shaowei Li, Han Wen, Wei Yang, Jiangtao Guo, Fan Yang
Summary: This study reports the presence of an endogenous cholesterol molecule inside the TRPV2 receptor, which antagonizes ligand activation and is removed by methyl-beta-cyclodextrin. Additionally, the study shows that estradiol can enhance TRPV2 activation. These findings provide a structural basis for understanding the regulation of TRPV2.
NATURE CHEMICAL BIOLOGY
(2023)
Article
Neurosciences
Sergio Lainez, Christoforos Tsantoulas, Martin Biel, Peter A. McNaughton
JOURNAL OF PHYSIOLOGY-LONDON
(2019)
Article
Anesthesiology
Benjamin L. Allen, Karli Montague-Cardoso, Raffaele Simeoli, Romain A. Colas, Silvia Oggero, Bruno Vilar, Peter A. McNaughton, Jesmond Dalli, Mauro Perretti, Emanuele Sher, Marzia Malcangio
Letter
Multidisciplinary Sciences
Bruno Vilar, Chun-Hsiang Tan, Peter A. McNaughton
Article
Anesthesiology
Graziele C. Zanata, Larissa G. Pinto, Nicole R. da Silva, Alexandre H. P. Lopes, Francisco F. B. de Oliveira, Ieda R. S. Schivo, Fernando Q. Cunha, Peter McNaughton, Thiago M. Cunha, Rangel L. Silva
Summary: The study found that kinin-kallikrein and renin-angiotensin systems, through B1, B2 and AT2 receptors, play a role in the induction of P-APS in mice, and AT2R antagonists are potential alternatives to prevent P-APS.
EUROPEAN JOURNAL OF PAIN
(2021)
Review
Neurosciences
Tamara Joelle Buijs, Peter Anthony McNaughton
FRONTIERS IN CELLULAR NEUROSCIENCE
(2020)
Article
Neurosciences
Mark N. Wallace, Christian J. Sumner, Joel I. Berger, Peter A. McNaughton, Alan R. Palmer
Summary: Tinnitus may be related to a decrease in the firing rate of high spontaneous firing rate fibers in the auditory nerve, with administration of high doses of sodium salicylate being an effective method to induce tinnitus in experimental animals. This leads to an increase in the proportion of medium spontaneous rate fibers and a decrease in the proportion of high spontaneous firing rate fibers.
NEUROSCIENCE LETTERS
(2021)
Article
Multidisciplinary Sciences
Hassan Morad, Suaib Luqman, Chun-Hsiang Tan, Victoria Swann, Peter A. McNaughton
Summary: The study demonstrates that neutrophils accurately navigate towards pathogens by activating TRPM2 ion channels to generate intracellular leading-edge calcium pulses. This mechanism is not only observed for hydrogen peroxide but also for other chemoattractants. Leading-edge calcium pulses are proposed as the universal drivers of the motile machinery involved in neutrophil chemotaxis.
SCIENTIFIC REPORTS
(2021)
Article
Neurosciences
Matthew Swire, Peggy Assinck, Peter A. McNaughton, David A. Lyons, Charles Ffrench-Constant, Matthew R. Livesey
Summary: HCN2 ion channels play a key role in regulating myelin sheath length in the central nervous system. Pharmacological blockade or genetic knockout of HCN2 can affect myelin sheath length, highlighting their importance in the relationship between neuronal activity and myelin formation.
JOURNAL OF NEUROSCIENCE
(2021)
Article
Biochemistry & Molecular Biology
Matthew Watson, Teresa B. Almeida, Arundhati Ray, Christina Hanack, Rory Elston, Joan Btesh, Peter A. McNaughton, Katherine Stott
Summary: Disordered scaffold proteins play an important role in orchestrating cellular processes through the interaction of Short Linear Motifs (SLiMs). One such protein, AKAP5, was found to interact with Calcineurin through multiple lower-affinity SLiMs. This interaction is similar to the binding of DNA-binding proteins to DNA, but involves the interaction between two proteins.
JOURNAL OF MOLECULAR BIOLOGY
(2022)
Article
Neurosciences
Christoforos Tsantoulas, Aidan Ng, Larissa Pinto, Anna P. Andreou, Peter A. McNaughton
Summary: Migraine is triggered by neuronal activity and can cause unilateral throbbing headache. HCN2 is identified as a critical trigger of migraine, and its inhibition can suppress pain sensation and neuronal activity.
JOURNAL OF NEUROSCIENCE
(2022)
Article
Immunology
Thiago Neves Vieira, Andre L. Lopes Saraiva, Rafaela Mano Guimaraes, Joao Paulo Mesquita Luiz, Larissa Garcia Pinto, Veridiana de Melo Rodrigues Avila, Luiz Ricardo Goulart, Jair Pereira Cunha-Junior, Peter Anthony McNaughton, Thiago Mattar Cunha, Juliano Ferreira, Cassia Regina Silva
Summary: This study found that the antagonist of AT(2)R has the potential to alleviate pain and inflammation in a mouse model of acute gout attack, suggesting it could be a potential therapeutic option for managing gout arthritis.
INFLAMMOPHARMACOLOGY
(2022)
Article
Biochemistry & Molecular Biology
Tamara J. Buijs, Bruno Vilar, Chun-Hsiang Tan, Peter A. McNaughton
Summary: Moderate coolness is sensed by TRPM8 ion channels in peripheral sensory nerves, but the mechanism by which noxious cold is detected remains elusive. In this study, two distinct mechanisms to detect noxious cold were discovered in somatosensory and sympathetic neurons. The first mechanism involves inhibition of a background outward current by cold, leading to membrane depolarization and activation of an inward current through voltage-dependent calcium channels. The second mechanism is independent of membrane voltage and involves the activation of ORAI ion channels by aggregation of STIM1, which is directly activated by cold and not by calcium store depletion.
Article
Multidisciplinary Sciences
Hassan O. J. Morad, Suaib Luqman, Larissa Garcia Pinto, Kevin P. Cunningham, Bruno Vilar, Georgia Clayton, Manu Shankar-Hari, Peter A. McNaughton
Summary: The antimalarial compound artemisinin has been identified as a potent inhibitor of neutrophil and macrophage chemotaxis induced by various chemotactic agents. It releases calcium from intracellular stores and selectively blocks the SERCA3 isoform. In mouse infection models, artemisinin suppresses neutrophil invasion and inhibits the release of cytokines/chemokines and NETs.
SCIENTIFIC REPORTS
(2022)
Article
Neurosciences
Shannon A. Bernard Healey, Ingrid Scholtes, Mark Abrahams, Peter A. McNaughton, David K. Menon, Michael C. Lee
Summary: HCN ion channels are important in mediating action potential firing in the heart and nervous system. Ivabradine, a nonselective HCN blocker, has shown potential as a treatment for neuropathic pain. In this study, increasing doses of ivabradine were administered to patients with chronic peripheral neuropathic pain, and a correlation between ivabradine dose and pain scores was observed.
Article
Neurosciences
Shannon A. Bernard Healey, Ingrid Scholtes, Mark Abrahams, Peter A. Mcnaughton, David K. Menon, Michael C. Lee
Summary: Studies suggest that ivabradine may be effective at higher doses, particularly in patients with diabetic neuropathic pain. Importantly, participants reported no adverse effects.