Article
Clinical Neurology
Miklos Lengyel, Dominika Hajdu, Alice Dobolyi, Judit Rosta, Gabor Czirjak, Maria Dux, Peter Enyedi
Summary: The study found that inhibition of TRESK increased TRPV1-mediated calcium signal in dorsal root ganglion neurons and potentiated capsaicin-induced increases in calcitonin gene-related peptide release and meningeal blood flow. Activation of TRESK decreased capsaicin sensitivity in sensory neurons, leading to an attenuation of capsaicin-induced increase in meningeal blood flow. In animals lacking TRESK, TRPV1-mediated nociceptive reactions were not affected by TRESK modulators.
Article
Pharmacology & Pharmacy
Dingding Liu, Lulu Chang, Jingru Wang, Qiang Zhu, Ning Jiang, Mudassar Azhar, Ayaz Ahmed, Guirong Zeng
Summary: This study evaluated the effect of Xiongmatang (XMT) extract on rats with migraine induced by inflammatory soup. The results showed that XMT extract improved the behavioral performance of rats and improved the pathological changes in the trigeminal nerve. Further experiments demonstrated that XMT extract regulated the activity of the TRPV1-CGRP/CGRP-R pathway.
FRONTIERS IN PHARMACOLOGY
(2022)
Article
Plant Sciences
Qian Yu, Yu Zhao, Xinyue Zhang, Wenjie Li, Hongyin Zhang, Songlan Piao, Guangzhe Li, Mingming Yan
Summary: Sanhuang ointment (SHO) has been found to have anti-inflammatory and anti-vascular permeability effects, which can effectively alleviate the symptoms of hemorrhoids.
JOURNAL OF ETHNOPHARMACOLOGY
(2024)
Article
Neurosciences
Mira T. Kronschlaeger, Anna S. M. Siegert, Felix J. Resch, Pradeep S. Rajendran, Baljit S. Khakh, Juergen Sandkuehler
Summary: Astrocytes in the dorsal horn of the spinal cord show fine-tuned differences across different layers to meet the demands of processing sensory information of varying modalities. While astrocytes in laminae I and II exhibit higher density and elevated expression levels of certain markers compared to those in lamina III, they share similar membrane properties, network formation, and intracellular calcium signaling characteristics.
Review
Anesthesiology
Lou Cathenaut, Remy Schlichter, Sylvain Hugel
Summary: Somatosensory information is efficiently processed in the spinal cord by frequency-tuned synapses, which display activity-dependent forms of short-term plasticity. These properties allow for powerful gain control in neuronal networks and contribute to the integration of nociceptive messages and the effectiveness of nonpharmacological analgesic procedures.
Article
Neurosciences
Jinrong Li, Md Sams Sazzad Ali, Christian H. Lemon
Summary: This study demonstrates communication between TRPV1-lineage fibers and taste neurons, supporting dependencies between gustatory and somatosensory hedonic representations.
JOURNAL OF NEUROSCIENCE
(2022)
Article
Immunology
Mario Heles, Petra Mrozkova, Dominika Sulcova, Pavel Adamek, Diana Spicarova, Jiri Palecek
Summary: The study revealed that elevated levels of CCL2 may severely weaken the opioid-induced inhibition of excitatory synaptic transmission through a microglia activation mechanism, while the delayed enhancement of neurotransmission after mu OR activation is dependent on TRPV1 receptor activation.
JOURNAL OF NEUROINFLAMMATION
(2021)
Article
Neurosciences
Renaud Jeffrey-Gauthier, Julien Bouyer, Mathieu Piche, Marie-Pascale Cote, Hugues Leblond
Summary: This study found that musculoskeletal injury may hinder locomotor recovery after SCI, with involvement of microglia in this effect, but without modulation of KCC2 expression.
EXPERIMENTAL NEUROLOGY
(2021)
Article
Biology
Mariantonella Colucci, Azzurra Stefanucci, Adriano Mollica, Anna Maria Aloisi, Francesco Maione, Stefano Pieretti
Summary: Formyl peptide receptor type 2 (FPR2/ALX) plays a crucial role in recognizing pathogen-associated molecular patterns and damage-associated molecular patterns. It is highly expressed in myeloid cells and various other cell types. Research suggests that FPR2/ALX may be involved in pain control in the spinal cord.
Article
Biochemistry & Molecular Biology
Gerlania de Oliveira Leite, Sacha Aubrey Alves Rodrigues Santos, Romerio Rodrigues dos Santos Silva, Claudener Souza Teixeira, Adriana Rolim Campos
Summary: The study shows that PPL lectin is effective in reducing nociceptive behavior in adult zebrafish, as well as in acute and chronic pain, indicating its potential pharmacological relevance.
Article
Biology
Xiaoyi Mo, Qiang Liu, Luna Gao, Chang Xie, Xin Wei, Peiyuan Pang, Quan Tian, Yue Gao, Youjing Zhang, Yuanyuan Wang, Tianchen Xiong, Bo Zhong, Dongdong Li, Jing Yao
Summary: 1,4-Dioxane potentiates TRPV1 channel and causes hyperalgesia in mice. The residue M572 in TRPV1 is crucial for the direct activation of the channel by 1,4-dioxane. TRPV1 acts as a co-receptor for 1,4-dioxane and dysregulates body nociceptive sensation.
Article
Biochemistry & Molecular Biology
Zhi-Hong Wen, Jhy-Shrian Huang, Yen-You Lin, Zhi-Kang Yao, Yu-Cheng Lai, Wu-Fu Chen, Hsin-Tzu Liu, Sung-Chun Lin, Yu-Chi Tsai, Tsung-Chang Tsai, Yen-Hsuan Jean
Summary: This study demonstrated that the marine-derived HDAC inhibitor panobinostat has chondroprotective effects on experimental OA rats, alleviating nociceptive behaviors, preventing cartilage degeneration, and regulating protein expressions in articular cartilage chondrocytes. These findings suggest that panobinostat may be a potential therapeutic drug for OA.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2021)
Article
Biology
Carmen Klein Herenbrink, Jonatan Fullerton Stoier, William Dalseg Reith, Abeer Dagra, Miguel Alejandro Cuadrado Gregorek, Reto B. Cola, Tommaso Patriarchi, Yulong Li, Lin Tian, Ulrik Gether, Freja Herborg
Summary: This study develops dopamine sensor cell lines expressing fluorescent reporters, which can be used to detect endogenous dopamine release, determine dopamine tissue content, and measure dopamine uptake and efflux. This versatile tool has a wide range of applications.
COMMUNICATIONS BIOLOGY
(2022)
Article
Pharmacology & Pharmacy
Fernanda Tibolla Viero, Patricia Rodrigues, Julia Maria Frare, Nathaly Andrighetto Ruviaro Da Silva, Marcella de Amorim Ferreira, Ana Merian Da Silva, Gabriele Cheiran Pereira, Juliano Ferreira, Micheli Mainardi Pillat, Guilherme Vargas Bocchi, Romina Nassini, Pierangelo Geppetti, Gabriela Trevisan
Summary: This study investigated the effects of sound stress on nociception and anxiety-related symptoms in mice. The results showed that sound stress led to alterations in pain sensitivity, anxiety-like symptoms, and exploratory behavior, with a more pronounced effect in female mice. Furthermore, these changes were alleviated by blocking CGRP receptors, and an increase in plasma inflammatory cytokines and CGRP levels was observed in stressed mice, with higher levels in female mice.
FRONTIERS IN PHARMACOLOGY
(2022)
Article
Clinical Neurology
Johanna Kleeberg-Hartmann, Birgit Vogler, Karl Messlinger
Summary: The study found that petasin and isopetasin can reduce CGRP release by inhibiting the activity of TRPA1 and TRPV1 receptor channels, potentially playing a role in the prophylactic effect against migraine. These results reveal the potential mechanisms by which petasins may reduce migraine attacks.
JOURNAL OF HEADACHE AND PAIN
(2021)
Article
Chemistry, Medicinal
Arthur Gomtsyan, Robert G. Schmidt, Erol K. Bayburt, Gregory A. Gfesser, Eric A. Voight, Jerome F. Daanen, Diana L. Schmidt, Marlon D. Cowart, Huaqing Liu, Robert J. Altenbach, Michael E. Kort, Bruce Clapham, Phil B. Cox, Anurupa Shrestha, Rodger Henry, David N. Whittern, Regina M. Reilly, Pamela S. Puttfarcken, Jill-Desiree Brederson, Ping Song, Bin Li, Susan M. Huang, Heath A. McDonald, Torben R. Neelands, Steve P. McGaraughty, Donna M. Gauvin, Shailen K. Joshi, Patricia N. Banfor, Jason A. Segreti, Mohamad Shebley, Connie R. Faltynek, Michael J. Dart, Philip R. Kym
JOURNAL OF MEDICINAL CHEMISTRY
(2016)
Article
Chemistry, Organic
Eric A. Voight, Jerome F. Daanen, Robert G. Schmidt, Arthur Gomtsyan, Michael J. Dart, Philip R. Kym
JOURNAL OF ORGANIC CHEMISTRY
(2016)
Article
Neurosciences
Steve McGaraughty, Katharine L. Chu, Jun Xu, Laura Leys, Richard J. Radek, Michael J. Dart, Arthur Gomtsyan, Robert G. Schmidt, Philip R. Kym, Jill-Desiree Brederson
JOURNAL OF NEUROPHYSIOLOGY
(2017)
Article
Physiology
A. Garami, E. Pakai, H. A. McDonald, R. M. Reilly, A. Gomtsyan, J. J. Corrigan, E. Pinter, D. X. D. Zhu, S. G. Lehto, N. R. Gavva, P. R. Kym, A. A. Romanovsky
Article
Hematology
Scott W. Mittelstadt, Richard A. Nelson, Jerome F. Daanen, Andrew J. King, Michael E. Kort, Philip R. Kym, Nathan L. Lubbers, Bryan F. Cox, James J. Lynch
BLOOD COAGULATION & FIBRINOLYSIS
(2012)
Review
Pharmacology & Pharmacy
Jill-Desiree Brederson, Philip R. Kym, Arpad Szallasi
EUROPEAN JOURNAL OF PHARMACOLOGY
(2013)
Article
Chemistry, Medicinal
Vince S. C. Yeh, David W. A. Beno, Sevan Brodjian, Michael E. Brune, Steven C. Cullen, Brian D. Dayton, Madhup K. Dhaon, Hugh D. Falls, Ju Gao, Nelson Grihalde, Philip Hajduk, T. Matthew Hansen, Andrew S. Judd, Andrew J. King, Russel C. Klix, Kelly J. Larson, Yau Y. Lau, Kennan C. Marsh, Scott W. Mittelstadt, Dan Plata, Michael J. Rozema, Jason A. Segreti, Eric J. Stoner, Martin J. Voorbach, Xiaojun Wang, Xili Xin, Gang Zhao, Christine A. Collins, Bryan F. Cox, Regina M. Reilly, Philip R. Kym, Andrew J. Souers
JOURNAL OF MEDICINAL CHEMISTRY
(2012)
Article
Chemistry, Medicinal
Eric A. Voight, Arthur R. Gomtsyan, Jerome F. Daanen, Richard J. Perner, Robert G. Schmidt, Erol K. Bayburt, Stanley DiDomenico, Heath A. McDonald, Pamela S. Puttfarcken, Jun Chen, Torben R. Neelands, Bruce R. Bianchi, Ping Han, Regina M. Reilly, Pamela H. Franklin, Jason A. Segreti, Richard A. Nelson, Zhi Su, Andrew J. King, James S. Polakowski, Scott J. Baker, Donna M. Gauvin, LaGeisha R. Lewis, Joseph P. Mikusa, Shailen K. Joshi, Connie R. Faltynek, Philip R. Kym, Michael E. Kort
JOURNAL OF MEDICINAL CHEMISTRY
(2014)
Article
Neurosciences
Cristiane de Oliveira, Andras Garami, Sonya G. Lehto, Eszter Pakai, Valeria Tekus, Krisztina Pohoczky, Beth D. Youngblood, Weiya Wang, Michael E. Kort, Philip R. Kym, Erika Pinter, Narender R. Gavva, Andrej A. Romanovsky
JOURNAL OF NEUROSCIENCE
(2014)
Article
Pharmacology & Pharmacy
Ashvani K. Singh, Yihong Fan, Corina Balut, Sara Alani, Arlene M. Manelli, Andrew M. Swensen, Ying Jia, Torben R. Neelands, Timothy A. Vortherms, Bo Liu, Xenia B. Searle, Xueqing Wang, Wenqing Gao, Tzyh-Chang Hwang, Hong Y. Ren, Douglas Cyr, Philip R. Kym, Katja Conrath, Chris Tse
JOURNAL OF PHARMACOLOGY AND EXPERIMENTAL THERAPEUTICS
(2020)
Article
Clinical Neurology
Matthew Rosebraugh, Eric A. Voight, Ehab M. Moussa, Feroz Jameel, Xiaochun Lou, Geoff G. Z. Zhang, Peter T. Mayer, Deanne Stolarik, Robert A. Carr, Brian P. Enright, Wei Liu, Maurizio F. Facheris, Philip R. Kym
Summary: This study demonstrates the effectiveness of continuous subcutaneous infusion of a soluble levodopa/carbidopa phosphate prodrug combination in delivering stable levodopa exposure, potentially treating Parkinson's disease patients who are not well controlled on oral medication. The prepared drugs show high water solubility, excellent chemical stability, and good tolerability in both animals and healthy volunteers. The prepared combination supports further clinical studies as a potentially transformative option for Parkinson's disease treatment.
ANNALS OF NEUROLOGY
(2021)
Article
Chemistry, Medicinal
Eric A. Voight, Stephen N. Greszler, Philip R. Kym
Summary: The paramount importance of synthetic organic chemistry in the pharmaceutical industry lies in the necessity to physically prepare designed molecules to obtain key data for the design-synthesis-data cycle, with medicinal chemists at the center. Synthesis specialists accelerate medicinal chemistry innovation by rapidly identifying and executing impactful synthetic methods, addressing the synthetic accessibility bottleneck. AbbVie’s Discovery Synthesis Groups (DSGs) like Centralized Organic Synthesis (COS) bridge the gap between discovery and process chemistry, providing tools and compounds to fuel the pipeline, showcasing key contributions in developing advanced drug candidates.
ACS MEDICINAL CHEMISTRY LETTERS
(2021)
Article
Biochemistry & Molecular Biology
Meena Patel, Hillary M. Peltier, Mark A. Matulenko, John R. Koenig, Marc J. C. Scanio, Rebecca J. Gum, Odile F. El-Kouhen, Meagan M. Fricano, Greta L. Lundgaard, Torben Neelands, Xu-Feng Zhang, Cenchen Zhan, Madhavi Pai, Nayereh Ghoreishi-Haack, Thomas Hudzik, Gary Gintant, Ruth Martin, Steve McGaraughty, Jun Xu, Daniel Bow, John C. Kalvass, Philip R. Kym, David A. DeGoey, Michael E. Kort
Summary: The voltage-gated sodium channel Na(v)1.7 is a promising target for pain treatment, and the discovery of 2-substituted quinolines and quinolones as potent small molecule Na(v)1.7 blockers has shown good efficacy and analgesic effects.
BIOORGANIC & MEDICINAL CHEMISTRY
(2022)
Article
Pharmacology & Pharmacy
Regina M. Reilly, Heath A. McDonald, Pamela S. Puttfarcken, Shailen K. Joshi, LaGeisha Lewis, Madhavi Pai, Pamela H. Franklin, Jason A. Segreti, Torben R. Neelands, Ping Han, Jun Chen, Patrick W. Mantyh, Joseph R. Ghilardi, Teresa M. Turner, Eric A. Voight, Jerome F. Daanen, Robert G. Schmidt, Arthur Gomtsyan, Michael E. Kort, Connie R. Faltynek, Philip R. Kym
JOURNAL OF PHARMACOLOGY AND EXPERIMENTAL THERAPEUTICS
(2012)
Article
Pharmacology & Pharmacy
Bruce R. Bianchi, Xu-Feng Zhang, Regina M. Reilly, Philip R. Kym, Betty B. Yao, Jun Chen
JOURNAL OF PHARMACOLOGY AND EXPERIMENTAL THERAPEUTICS
(2012)