Review
Environmental Sciences
Ines Klein, Helmar C. Lehmann
Summary: Peripheral neuropathy is a common side effect of chemotherapy, affecting up to 60% of cancer patients. Paclitaxel induces neuropathy in gynecological and urological cancer patients, leading to cell death and affecting both central and peripheral nervous system cells. Symptoms include pain and numbness in hands and feet, with pathomechanisms involving axonal damage and disrupted axonal transport.
Article
Multidisciplinary Sciences
Grace Ji-eun Shin, Maria Elena Pero, Luke A. Hammond, Anita Burgos, Atul Kumar, Samantha E. Galindo, Tanguy Lucas, Francesca Bartolini, Wesley B. Grueber
Summary: Chemotherapy-induced peripheral neuropathy (CIPN) is a major side effect from cancer treatment with no known prevention or cure. Studying a genetically tractable Drosophila model and mouse sensory neurons, researchers have identified potential protective pathways against CIPN, shedding light on the mechanisms underlying this condition.
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
(2021)
Article
Immunology
Martial Caillaud, Nipa H. Patel, Alyssa White, Mackinsey Wood, Katherine M. Contreras, Wisam Toma, Yasmin Alkhlaif, Jane L. Roberts, Tammy H. Tran, Asti B. Jackson, Justin Poklis, David A. Gewirtz, M. Imad Damaj
Summary: The study demonstrated the therapeutic potential of fibrates, specifically fenofibrate and choline fenofibrate, in reversing and preventing pain sensitivity in peripheral neuropathies associated with paclitaxel treatment. Additionally, these fibrates did not diminish the antitumoral effects of paclitaxel, suggesting a potential for their pharmacological repurposing in PIPN.
BRAIN BEHAVIOR AND IMMUNITY
(2021)
Article
Medicine, General & Internal
David Mizrahi, Susanna B. Park, Tiffany Li, Hannah C. Timmins, Terry Trinh, Kimberley Au, Eva Battaglini, David Wyld, Robert D. Henderson, Peter Grimison, Helen Ke, Peter Geelan-Small, Julie Marker, Brian Wall, David Goldstein
Summary: Chemotherapy-induced peripheral neuropathy (CIPN) is a debilitating adverse effect of neurotoxic cancer treatments, and this study suggests that participants with low pretreatment hemoglobin, higher body mass index, older age, and female sex were more likely to develop CIPN posttreatment after receiving paclitaxel or oxaliplatin chemotherapy. Future research should explore whether these risk factors are associated with a higher incidence of CIPN development.
Article
Oncology
Hannah C. Timmins, Tiffany Li, Terry Trinh, Matthew C. Kiernan, Michelle Harrison, Frances Boyle, Michael Friedlander, David Goldstein, Susanna B. Park
Summary: The study reveals that weekly paclitaxel treatment can induce neuropathy early on and patients may require closer monitoring. Dose reduction does not necessarily result in better neuropathy outcomes, with individual risk factors also playing a significant role.
Article
Oncology
Martial Caillaud, Nipa H. Patel, Wisam Toma, Alyssa White, Danielle Thompson, Jared Mann, Tammy H. Tran, Jane L. Roberts, Justin L. Poklis, John W. Bigbee, Xianjun Fang, David A. Gewirtz, M. Imad Damaj
Summary: The study demonstrates the therapeutic potential of fenofibrate in preventing paclitaxel-induced peripheral neuropathy by reducing pain symptoms through modulation of PPAR-alpha expression and decreasing neuroinflammation. This suggests a possible repurposing of fenofibrate in the clinic for preventing paclitaxel-induced neuropathy.
Review
Biochemistry & Molecular Biology
Takehiro Kawashiri, Mizuki Inoue, Kohei Mori, Daisuke Kobayashi, Keisuke Mine, Soichiro Ushio, Hibiki Kudamatsu, Mayako Uchida, Nobuaki Egashira, Takao Shimazoe
Summary: Paclitaxel is essential in chemotherapy for various cancers, but its frequent side effect of peripheral neuropathy poses challenges. While many drugs have shown neuroprotective effects in animal models, few have demonstrated efficacy in clinical trials. Therefore, enhancing translational research is crucial for bridging the gap between preclinical and clinical studies in addressing paclitaxel-induced peripheral neuropathy.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2021)
Article
Medicine, Research & Experimental
Kosar Hooshmand, David Goldstein, Hannah C. Timmins, Tiffany Li, Michelle Harrison, Michael L. Friedlander, Craig R. Lewis, Justin G. Lees, Gila Moalem-Taylor, Boris Guennewig, Susanna B. Park, John B. Kwok
Summary: This study identified genetic loci associated with paclitaxel-induced chemotherapy-induced peripheral neuropathy (CIPN) through a genome-wide association study. Further analysis revealed the potential involvement of axon development and regeneration pathways in CIPN.
JOURNAL OF TRANSLATIONAL MEDICINE
(2022)
Article
Immunology
Anil Kumar Kalvala, Arvind Bagde, Peggy Arthur, Sunil Kumar Surapaneni, Nimma Ramesh, Aakash Nathani, Mandip Singh
Summary: The purpose of this study was to evaluate the protective effects of phytocannabinoids, synthetic cannabidiol (CBD), and tetrahydrocannabivarin (THCV), both individually and in combination, against Paclitaxel-induced peripheral neuropathy (PIPN) in mice. The combination of CBD and THCV showed a twofold improvement in neurobehavioral symptoms compared to individual treatments. The study identified specific protein targets and mechanisms involved in the therapeutic effects of CBD and THCV. Furthermore, the combination therapy protected neurons in mice by modulating mitochondrial function and through the activation of specific receptors.
INTERNATIONAL IMMUNOPHARMACOLOGY
(2022)
Article
Biotechnology & Applied Microbiology
Weiwei Zhang, Yinggang Xu, Xiaoqing Shi, Xiaofeng Huang, Rui Chen, Haiping Xu, Wenjie Shi, Xinyu Wan, Ye Wang, Jinzhi He, Cuiying Li, Jue Wang, Xiaoming Zha
Summary: This study retrospectively compared the efficacy and safety of two potential neoadjuvant systemic treatment drugs, liposomal paclitaxel (Lps-P) and nanoparticle albumin-bound paclitaxel (Nab-P), in breast cancer. The results showed that more participants who received Nab-P had no signs of cancer in their breast and axillary lymph nodes than participants who received Lps-P. Although Nab-P can cause a higher incidence and severity of peripheral sensory neuropathy (PSN), most symptoms are temporary and reversible. In conclusion, Nab-P might be superior to Lps-P for neoadjuvant systemic treatment of breast cancer.
Review
Oncology
Alisha Joan Leen, Dominic Wei Ting Yap, Chong Boon Teo, Benjamin Kye Jyn Tan, Alex Molassiotis, Hiroshi Ishiguro, Sarah Wei Xian Fan, Raghav Sundar, Yu Yang Soon, Aishwarya Bandla
Summary: The study found that non-pharmacological neuroprotective interventions are more effective than pharmacological methods in preventing PIPN, leading to a significant reduction in the incidence of PIPN.
FRONTIERS IN ONCOLOGY
(2022)
Article
Oncology
Ciao-Sin Chen, Ellen M. Lavoie Smith, Kathleen A. Stringer, N. Lynn Henry, Daniel L. Hertz
Summary: This study investigates whether sensory and motor chemotherapy-induced peripheral neuropathy (CIPN) are distinct subtypes with different predictive biomarkers in breast cancer patients receiving paclitaxel. The findings suggest that sensory and motor CIPN co-occur and may not have differentiating metabolic biomarkers. Further research is needed to validate these findings and improve the prediction, prevention, and treatment of CIPN.
BREAST CANCER RESEARCH AND TREATMENT
(2022)
Article
Neurosciences
Pavel Adamek, Mario Heles, Anirban Bhattacharyya, Monica Pontearso, Jakub Slepicka, Jiri Palecek
Summary: The novel FDA-approved PI3K delta/gamma isoform-specific inhibitor duvelisib shows promising ability in preventing paclitaxel-induced peripheral neuropathy, indicating its potential for use in human medicine.
JOURNAL OF NEUROSCIENCE
(2022)
Article
Pharmacology & Pharmacy
Yuhao Xu, Zongsheng Jiang, Xiaowei Chen
Summary: Paclitaxel is a widely used chemotherapeutic agent, but its use often leads to severe neuropathic pain that is difficult to manage. The mechanisms underlying paclitaxel-induced neuropathic pain are still unclear, but evidence suggests correlations with ion channels, neuroinflammation, and mitochondrial damage.
EUROPEAN JOURNAL OF PHARMACOLOGY
(2022)
Article
Oncology
Su-Hyun Kim, Ki Hoon Kim, Jae-Won Hyun, Ji Hyun Kim, Sang-Soo Seo, Ho Jin Kim, Sang-Yoon Park, Myong Cheol Lim
Summary: This study evaluated the potential of sNfL and sBDNF as reliable biomarkers for PIPN. The study found that sNfL levels were associated with the severity of PIPN and may indicate PIPN progression. Additionally, low sBDNF levels within 6 months after chemotherapy may affect PIPN recovery.
FRONTIERS IN ONCOLOGY
(2022)
Article
Anesthesiology
Lisa Boinon, Jie Yu, Cynthia L. Madura, Aude Chefdeville, Douglas L. Feinstein, Aubin Moutal, Rajesh Khanna
Summary: CRMP2 is a key regulator of synaptic transmission and contributes to the transition of physiological pain into pathological pain.
Article
Multidisciplinary Sciences
Yoshiaki Suzukia, Takumi Ozawa, Tomo Kurata, Nanami Nakajima, Gerald W. Zamponi, Wayne R. Giles, Yuji Imaizumi, Hisao Yamamura
Summary: Elevation of intracellular Ca2+ concentration activates Ca2+/calmodulin-dependent kinases (CaMK) and promotes gene transcription. The complex of Ca(v)1.2/CaMKK2/CaMK1a located in caveolae plays a crucial role in vascular myocytes, converting changes in Ca2+ influx into gene transcription, ultimately leading to macrophage accumulation and media remodeling.
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
(2022)
Article
Pharmacology & Pharmacy
Paz Duran, Santiago Loya-Lopez, Dongzhi Ran, Cheng Tang, Aida Calderon-Rivera, Kimberly Gomez, Harrison J. Stratton, Sun Huang, Ya-ming Xu, E. M. Kithsiri Wijeratne, Samantha Perez-Miller, Zhiming Shan, Song Cai, Anna T. Gabrielsen, Angie Dorame, Kyleigh A. Masterson, Omar Alsbiei, Cynthia L. Madura, Guoqin Luo, Aubin Moutal, John Streicher, Gerald W. Zamponi, A. A. Leslie Gunatilaka, Rajesh Khanna
Summary: This study identified argentatin C, a compound derived from the Native American medicinal plant Parthenium incanum, which can block the activity of voltage-gated sodium and calcium channels and has potential as a novel treatment for painful conditions. Experimental results demonstrated that argentatin C decreased ion currents and excitability in sensory neurons and relieved postsurgical pain in a mouse model. Therefore, argentatin C may serve as an alternative therapy for chronic pain management.
BRITISH JOURNAL OF PHARMACOLOGY
(2023)
Article
Pharmacology & Pharmacy
Erika K. Harding, Ivana A. Souza, Maria A. Gandini, Vinicius M. Gadotti, Md Yousof Ali, Sun Huang, Flavia T. T. Antunes, Tuan Trang, Gerald W. Zamponi
Summary: Cannabinoids are a potential therapy for chronic pain, but their analgesic efficacy is often not reported in clinical trials. This study found that cannabinoids can produce analgesia by inhibiting voltage gate calcium channels, and different cannabinoids target different types of channels through distinct mechanisms. The cannabinoid CBD binds to and occludes the pore of the Ca(v)3.2 channel, alleviating inflammatory and neuropathic pain.
BRITISH JOURNAL OF PHARMACOLOGY
(2023)
Article
Biochemistry & Molecular Biology
Md Yousof Ali, Vinicius M. Gadotti, Sun Huang, Agustin Garcia-Caballero, Flavia T. T. Antunes, Hyun Ah Jung, Jae Sue Choi, Gerald W. Zamponi
Summary: Cav3.2 channels are important in pain transmission, and ICA-II can inhibit these channels and has analgesic effects in mice.
ACS CHEMICAL NEUROSCIENCE
(2023)
Article
Biochemistry & Molecular Biology
Md Yousof Ali, Se Eun Park, Su Hui Seong, Gerald W. Zamponi, Hyun Ah Jung, Jae Sue Choi
Summary: This study found that ursonic acid (UNA) and ursolic acid (ULA), two main compounds in Artemisia montana, have inhibitory effects on protein tyrosine phosphatase 1B (PTP1B) and alpha-glucosidase. UNA also increases glucose uptake and decreases PTP1B expression by activating the IRS-1/PI3K/Akt/GSK-3 signaling pathway, showing potential for the treatment of diabetes and its complications.
CHEMICO-BIOLOGICAL INTERACTIONS
(2023)
Editorial Material
Neurosciences
Tyler S. Nelson, Rajesh Khanna
Article
Physiology
Abdulaziz M. M. Alaklabi, Eder Gambeta, Gerald W. W. Zamponi
Summary: Trigeminal neuralgia is a rare and debilitating disorder that leads to severe pain attacks and poor quality of life. A recent study discovered a new missense mutation in the CACNA1G gene, which encodes the Ca(V)3.1 calcium channel, suggesting its important role in trigeminal pain.
PFLUGERS ARCHIV-EUROPEAN JOURNAL OF PHYSIOLOGY
(2023)
Article
Neurosciences
Vinicius de Maria Gadotti, Flavia Tasmin Techera Antunes, Gerald W. Zamponi
Summary: Spinally delivered ?(9)-THC produces analgesic effects by acting on T-type calcium channels rather than activating spinal cannabinoid receptors.
Article
Cell Biology
Tatiana Brustovetsky, Rajesh Khanna, Nickolay Brustovetsky
Summary: Mitochondrial bioenergetics and dynamics, specifically alterations in morphology and motility, play vital roles in the response of neurons to energy requirements in health and Alzheimer's disease (AD). The hyperphosphorylation of collapsin response mediator protein 2 (CRMP2) in AD disrupts its interaction with proteins regulating mitochondrial morphology and motility, resulting in increased Drp1 recruitment to mitochondria, augmented mitochondrial fragmentation, and reduced mitochondrial motility. The small molecule (S)-lacosamide ((S)-LCM) decreases CRMP2 phosphorylation, restores its interaction with related proteins, and improves mitochondrial dynamics and neuronal survival in AD.
Article
Chemistry, Multidisciplinary
Ya-ming Xu, E. M. Kithsiri Wijeratne, Aida Calderon-Rivera, Santiago Loya-Lopez, Samantha Perez-Miller, Rajesh Khanna, A. A. Leslie Gunatilaka
Summary: Four new triterpenes were isolated from Parthenium incanum and their structures were determined. These compounds were found to decrease the excitability of dorsal root ganglia neurons. The binding sites of these compounds in pain-relevant voltage-gated sodium and calcium channels were evaluated, and preliminary structure-activity relationships were established.
Article
Neurosciences
Robin N. Stringer, Leos Cmarko, Gerald W. Zamponi, Michel De Waard, Norbert Weiss
Summary: T-type calcium channelopathies are a group of human disorders caused or exacerbated by mutations in genes encoding T-type calcium channels. A new mutation in the CACNA1H gene encoding the Ca(v)3.2 T-type calcium channel was found in a patient with epilepsy and hearing loss, the first CACNA1H mutation associated with a sensorineural hearing condition. This mutation results in minor gating alterations and enhanced sensitivity to external pH change in the channel.
Article
Neurosciences
Heloisa Alonso-Matielo, Zizhen Zhang, Eder Gambeta, Junting Huang, Lina Chen, Gabriel Oliveira de Melo, Camila Squarzoni Dale, Gerald W. Zamponi
Summary: This study found inhibitory neurons projecting from the posterior insula to the anterior cingulate cortex, and stimulation of these projections did not affect mechanical nociception but induced affective responses.
Article
Neurosciences
Daniel F. Martins, Victor Sorrentino, Leidiane Mazzardo-Martins, William R. Reed, Adair R. S. Santos, Vinicius M. Gadotti, Gerald W. Zamponi
Summary: The present study aimed to investigate the role of Cav3.2 T-type channels in mediating the antihyperalgesic effects of joint manipulation (JM) therapy. Using a chronic constriction injury model in mice, we demonstrated that JM produced long-lasting mechanical antihyperalgesia, which was abolished in Cav3.2 null mice. Additionally, we found that JM displayed a similar analgesic profile to the fatty acid amide hydrolase inhibitor URB597, suggesting a possible shared mechanism of action involving endocannabinoids. Overall, our findings contribute to the understanding of the analgesic mechanisms of JM.
Review
Physiology
Norbert Weiss, Gerald W. Zamponi
Summary: T-type calcium channels play crucial roles in both neuronal and non-neuronal systems, and their functions depend on the interaction with other proteins. This review provides a comprehensive exploration of the current understanding of T-type channel interactors and highlights their potential for drug-based therapeutic interventions.
PFLUGERS ARCHIV-EUROPEAN JOURNAL OF PHYSIOLOGY
(2023)