Article
Multidisciplinary Sciences
Ryoichi Tashima, Keisuke Koga, Yu Yoshikawa, Misuzu Sekine, Moeka Watanabe, Hidetoshi Tozaki-Saitoh, Hidemasa Furue, Toshiharu Yasaka, Makoto Tsuda
Summary: Identified inhibitory interneurons in the spinal dorsal horn play a crucial role in converting touch-sensing A beta fiber signals into pain-like behavioral responses, and enhancing their activity may offer a novel strategy for treating neuropathic allodynia.
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
(2021)
Article
Neurosciences
Eric Brown, Ayma F. Malik, Elizabeth R. Moese, Abigail F. McElroy, Angelo C. Lepore
Summary: Neuropathic pain (NP) is a common and debilitating comorbidity of spinal cord injury (SCI). This study investigates the neural activity changes in the pain circuitry following cervical spinal cord injury. The findings reveal complex changes in neuronal activation, with increased activation in some neurons and decreased activation in inhibitory neurons.
JOURNAL OF NEUROSCIENCE
(2022)
Article
Multidisciplinary Sciences
Tyler S. Nelson, Ghanshyam P. Sinha, Diogo F. S. Santos, Peter Jukkola, Pranav Prasoon, Michelle K. Winter, Ken E. McCarson, Bret N. Smith, Bradley K. Taylor
Summary: Peripheral nerve injury enhances the excitability of Y1-INs in the spinal cord dorsal horn, leading to the development of allodynia and affective pain. Inhibition of Y1-INs or administration of Y1 agonists can alleviate allodynic symptoms. Conditional deletion of Npy1r in dorsal horn neurons prevents the anti-hyperalgesic effects of intrathecal Y1 agonists. These findings suggest that Y1-INs in the spinal cord are a promising target for the treatment of neuropathic pain.
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
(2022)
Article
Cell Biology
Fumihiro Saika, Shinsuke Matsuzaki, Shiroh Kishioka, Norikazu Kiguchi
Summary: The study focuses on investigating the sex-dependent roles of microglia in pain hypersensitivity, highlighting the importance of understanding the molecular aspects of spinal microglia regulation in pain. The results showed that chemogenetic activation of spinal microglia resulted in pain hypersensitivity in male mice, with sex differences observed in the upregulation of reactive microglia-dominant molecules and response to microglia depletion using pexidartinib.
Article
Medicine, Research & Experimental
Marc A. Russo, Willem Volschenk, Dominic Bailey, Danielle M. Santarelli, Elizabeth Holliday, Daniel Barker, Jason Dizon, Brett Graham
Summary: This study demonstrates the safety and efficacy of a novel paresthesia-free stimulation waveform for the treatment of chronic neuropathic low back pain. The waveform is compatible with all current commercial SCS systems and resulted in significant improvement in pain scores, quality of life, and patient satisfaction.
Article
Pharmacology & Pharmacy
Zhifeng Huang, Zijing Ding, Yangting Xu, Caiyun Xi, Liqiong He, Hui Luo, Qulian Guo, Changsheng Huang
Summary: Regulation of gene transcription in the spinal dorsal horn (SDH) through the transcription factor STAT2 plays a crucial role in the development of neuropathic pain. Chronic constriction injury of the rat sciatic nerve led to the downregulation of nuclear STAT2 in the SDH, which was associated with increased microglial activation and the development of neuropathic pain. In addition, siRNA-induced downregulation of STAT2 promoted microglial activation and pro-inflammatory cytokine expression in the SDH. Restoring nuclear expression of STAT2 could potentially be a therapeutic pathway for treating neuropathic pain.
FRONTIERS IN PHARMACOLOGY
(2023)
Review
Neurosciences
Lonne Heijmans, Martijn R. Mons, Elbert A. Joosten
Summary: This systematic review explores the involvement of the serotonergic system in modulating pain signaling, with a focus on both healthy adult rodents and those with chronic neuropathic pain. It highlights the role of specific serotonin receptors in inhibiting or facilitating pain modulation, and suggests that targeting these receptors could lead to improved pharmacological or neuromodulatory treatments for neuropathic pain. Additionally, the study identifies the descending serotonergic system as a key target for mechanism-based pain relief, particularly in the context of spinal cord stimulation.
Review
Clinical Neurology
Hemant Kumar, Ankita Bhagwani, Manjeet Chopra
Summary: Traumatic spinal cord injury can result in long-lasting complications such as chronic neuropathic pain and spasticity, which significantly impact the daily activities of patients. Current medical treatments for SCI-related neuropathic pain are limited due to the complex mechanisms involved, but restoring inhibitory GABAergic tone and preventing excitotoxicity may provide neuroprotective and analgesic effects.
Review
Neurosciences
Wu Zhou, Zhiping Xie, Chengcai Li, Zelong Xing, Shenke Xie, Meihua Li, Jianguo Yao
Summary: Neuropathic pain is a common symptom of many diseases, and the mechanisms underlying its onset and persistence are unclear, leading researchers to focus on the BDNF signaling pathway in the spinal dorsal horn.
NEUROSCIENCE LETTERS
(2021)
Article
Biochemistry & Molecular Biology
Kwan Yeop Lee, Dongchul Lee, Zachary B. Kagan, Dong Wang, Kerry Bradley
Summary: The study found that low-intensity 10 kHz SCS can inhibit pain-sensory processing in the spinal DH by activating inhibitory interneurons, resulting in paresthesia-free pain relief.
Article
Neurosciences
Laura Medlock, Kazutaka Sekiguchi, Sungho Hong, Salvador Dura-Bernal, William W. Lytton, Steven A. Prescott
Summary: Pain-related sensory input is processed in the spinal dorsal horn (SDH) before being relayed to the brain, influencing how stimuli are perceived as painful. Researchers developed a computational model constrained by experimental data to explore SDH function, which reproduced characteristic firing patterns of spinal neurons and responded consistently to inhibition reduction and specific neuron type ablation.
JOURNAL OF NEUROSCIENCE
(2022)
Article
Toxicology
Masatake Fujimura, Fusako Usuki, Atsushi Nakamura
Summary: The study revealed that MeHg exposure caused neurological damage in rats, leading to neuropathic pain, mainly through the activation of microglia in the dorsal horn. Furthermore, analysis of the cerebral cortex showed that MeHg exposure could result in the formation of new cortical circuits in specific areas, leading to hyperalgesia/allodynia.
ARCHIVES OF TOXICOLOGY
(2021)
Article
Cell Biology
Tadayuki Ishibashi, Daichi Sueto, Yu Yoshikawa, Keisuke Koga, Ken Yamaura, Makoto Tsuda
Summary: This study identified an inhibitory interneuron subset in the spinal dorsal horn that is depolarized by noradrenaline (NA) and showed that alpha(1B)-adrenoceptors (ARs) and AAV-NpyP(+) neurons are critical targets for spinal NA and necessary for the therapeutic effect of duloxetine on neuropathic pain.
Article
Neurosciences
Eric Brown, Aditi Falnikar, Nicolette Heinsinger, Lan Cheng, Carrie E. Andrews, Michael DeMarco, Angelo C. Lepore
Summary: The study revealed significant MM phi heterogeneity within and across pain transmission locations after SCI, including a prominent pro-inflammatory MM phi response in the sDH of cervical spinal cord. These data suggest a possible role for MM phi in DH neuron hyperexcitability and NP.
EXPERIMENTAL NEUROLOGY
(2021)
Article
Chemistry, Multidisciplinary
Ting Xu, Jing Wang, Yan Wu, Jia-Yan Wu, Wei-Cheng Lu, Meng Liu, Su-Bo Zhang, Dan Xie, Wen-Jun Xin, Jing-Dun Xie
Summary: This study investigates the role of N4-Acetylcytidine (ac4C) in neuropathic pain. Researchers discover that NAT10 mediates the increase in ac4C modification of Vegfa mRNA, facilitating the binding of polysomes, leading to enhanced translation efficiency. The upregulated VEGFA contributes to neuropathic pain by inducing central sensitivity. These findings may suggest a novel therapeutic approach in patients with neuropathic pain.
Review
Nanoscience & Nanotechnology
Saurabh Shah, Paras Famta, Vinod Tiwari, Arun K. Kotha, Rama Kashikar, Mahavir Bhupal Chougule, Young Hun Chung, Nicole F. Steinmetz, Mohammad Uddin, Shashi Bala Singh, Saurabh Srivastava
Summary: This article reviews and discusses the interplay between tumor microenvironment and the immunological cascade and how it can be utilized to develop nanoparticle-based cancer vaccines and immunotherapies. Nanoparticles and proteinaceous vaccines have enormous potential in cancer therapy.
WILEY INTERDISCIPLINARY REVIEWS-NANOMEDICINE AND NANOBIOTECHNOLOGY
(2023)
Article
Biochemistry & Molecular Biology
Digambar Kumar Waiker, Akash Verma, Gajendra T. Akhilesh, T. A. Gajendra, Namrata Singh, Anima Roy, Hagera Dilnashin, Vinod Tiwari, Surendra Kumar P. Trigun, Surya P. Singh, Sairam Krishnamurthy, Prem Lama, Vincent Jo Davisson, Sushant Kumar Shrivastava
Summary: This study successfully designed and synthesized a new class of compounds for the treatment of Alzheimer's disease (AD) through a multitargeted directed ligand design approach. Compound 5d and 5f showed inhibitory activity against key enzymes involved in AD pathology and reduced the aggregation of Aβ. They also demonstrated neuroprotective effects and improved learning and memory behaviors in AD mouse models.
ACS CHEMICAL NEUROSCIENCE
(2023)
Article
Biochemistry & Molecular Biology
Priyanka Bose, Manoj K. Jaiswal, Sumit K. Singh, Rakesh K. Singh, Vinod K. Tiwari
Summary: In nature, glycan chains called sialic acids or nuraminic acids cover most cells and have long been recognized for their therapeutic importance. Sialic acid-containing glycans play a crucial role on cell surfaces, modulating and mediating various cellular interactions. Understanding the interaction between sialo-proteins and their roles in vertebrates has had a significant impact on medicine.
CARBOHYDRATE RESEARCH
(2023)
Article
Pharmacology & Pharmacy
Shivani Jaiswal, Vinod Akhilesh, Vinod Tiwari, Senthil Raja Ayyannan
Summary: The isatin-derived carbohydrazone, SIH 3, showed significant anti-nociceptive activity in the neuropathic pain model without altering locomotor activity. It also displayed excellent safety profile in acute oral toxicity study and exhibited antioxidant effect in oxidative stress induced by chronic constrictive injury.
PHARMACOLOGICAL REPORTS
(2023)
Article
Chemistry, Organic
Sunil Kumar, Mangal S. Yadav, Sumit K. Singh, Sanchayita Rajkhowa, Vinod K. Tiwari
Summary: A modular and reliable click approach was used to synthesize lactose- and galactose-coated calixarenecored G(1) and G(2) generation glycodendrimers efficiently. The characterization of the developed calixarene glycodendrimers was performed using extensive spectral analysis including NMR (H-1 and C-13), MS, IR, and SEC data.
Article
Biochemistry & Molecular Biology
Priyanka Bose, Anand K. Agrahari, Rajan Singh, Mala Singh, Sunil Kumar, Rakesh K. Singh, Vinod K. Tiwari
Summary: A click-inspired piperazine glycoconjugate was developed to synthesize water-soluble and biocompatible motifs. This study focused on designing and synthesizing versatile sugar-appended triazoles using "Click Chemistry", and evaluated their pharmacological properties on cyclin-dependent kinases (CDKs) and cytotoxicity on cancer cells through in silico and in vitro approaches, respectively. The galactose- and mannose-derived piperazine conjugates were identified as promising motifs. The galactosyl bis-triazolyl piperazine analogue 10b was found to be the most interactive with CDKs and showed significant anticancer activity.
CARBOHYDRATE RESEARCH
(2023)
Review
Chemistry, Multidisciplinary
Manoj K. Jaiswal, Vinod K. Tiwari
Summary: Click Chemistry is a modular, rapid, and reliable tool used for the regioselective 1,2,3-triazole forming [3+2] reaction of organic azide and terminal alkyne. It is widely explored in various emerging research domains. The intramolecular click chemistry, which involves metal-catalyzed cyclization, organo-catalyzed cyclization, and thermal-induced topochemical reaction, is less addressed compared to the intermolecular metal variant. Recent approaches on intramolecular azide-alkyne cycloaddition 'Click Chemistry' and their emerging applications in the development of diverse molecules are reported.
Article
Chemistry, Multidisciplinary
Manoj K. Jaiswal, Abhishek Gupta, Mangal S. Yadav, Vinay K. Pandey, Vinod K. Tiwari
Summary: A novel organocatalyzed [3+2] cycloaddition reaction has been developed for the construction of 1,5-disubstituted triazolyl glycoconjugates. The reaction involves the use of Schreiner thiourea organocatalysts to activate nitroolefins through double hydrogen bonding. This metal-free and acid-free synthetic protocol is operationally simple, regioselective, and complements the classical RuAAC catalyzed synthesis of 1,5-disubstituted 1,2,3-triazoles. By using catalytic amounts of the Schreiner thiourea organocatalyst, a wide range of organic azides can react with nitroolefins to produce diverse 1,5-disubstituted 1,2,3-triazoles in good yields with excellent regioselectivity.
CHEMISTRY-A EUROPEAN JOURNAL
(2023)
Article
Immunology
Anagha Gadepalli, Obulapathi Ummadisetty, Akhilesh, Deepak Chouhan, Anmol, Vinod Tiwari
Summary: This study demonstrates the therapeutic effect of loperamide, a peripherally acting mu-opioid receptor agonist, on neuropathic pain in rats and elucidates its underlying mechanism.
INTERNATIONAL IMMUNOPHARMACOLOGY
(2023)
Article
Chemistry, Organic
Sumit K. Singh, Sunil Kumar, Mangal S. Yadav, Abhishek Gupta, Vinod K. Tiwari
Summary: This report describes a convenient method for the Cu(I)-catalyzed Sonogashira cross-coupling reaction of aryl/heteroaryl halides and alkynyl sugars using a glycohybrid ligand. The method has notable features, including low catalytic loading, cost-effectiveness, and a wide substrate scope.
JOURNAL OF ORGANIC CHEMISTRY
(2023)
Article
Chemistry, Organic
Sumit K. Singh, Sunil Kumar, Mangal S. Yadav, Subrato Bhattacharya, Vinod K. Tiwari
Summary: This report describes a convenient Cu(I)-catalyzed tandem synthesis method for the efficient synthesis of dihydrophenanthridinediones and substituted isoquinolinones using glycosyl 1,2,3-triazole-based pyridinamide ligands. The method successfully forms biologically relevant heterocyclic scaffolds in high yields through intermolecular C-C cross-coupling followed by intramolecular cyclization. Notable features of this method include low catalytic loading, use of cost-effective and biocompatible ligands, high reaction yield, and easily accessible starting materials, making it a versatile protocol.
SYNTHESIS-STUTTGART
(2023)
Review
Chemistry, Organic
Mangal S. Yadav, Abhishek Gupta, Priyanka Bose, Anoop S. Singh, Prabhu P. Mohapatra, Vinod K. Tiwari
Summary: N-Acylbenzotriazoles are important synthons in organic synthesis and can serve as alternative acylating agents in various organic transformations. This review summarizes the preparation methods of N-Acylbenzotriazole derivatives and their diverse applications, highlighting their ability to conveniently synthesize biologically important organic compounds as alternative acylating agents. The significance of using benzotriazole ring cleavage methodology in compound synthesis is also emphasized.
Article
Immunology
Deepak Akhilesh, Deepak Chouhan, Obulapathi Ummadisetty, Nivedita Verma, Vinod Tiwari
Summary: Chemotherapy-induced neuropathic pain is a disabling complication that affects patients' quality of life. This study found that bergenin effectively reduces neuropathic pain by modulating TRPA1/TRPV1/NR2B signaling pathway. The findings suggest that bergenin could be a promising therapeutic approach for chemotherapy-induced neuropathic pain.
INTERNATIONAL IMMUNOPHARMACOLOGY
(2023)
Article
Endocrinology & Metabolism
Ankit Uniyal, Anuj Mehta, Vinod Tiwari
Summary: Chemotherapy-induced neuropathic pain (CINP) is a therapeutic challenge with no approved drugs or effective treatments. This study established and validated a combination-based chemotherapeutic model of peripheral neuropathy, demonstrating heightened and prolonged hypersensitivity compared to the traditional paclitaxel-induced neuropathic pain model. Pharmacological investigations showed that gabapentin treatment mitigated pain hypersensitivity and reversed cellular and molecular changes in the rats. This model provides a potential alternative platform for screening analgesic drugs targeted at CINP.
METABOLIC BRAIN DISEASE
(2023)