Advantx Pharmaceuticals Inc.’s therapeutic candidate ADV502 NCP for Neuropathic Cancer Pain is the first pharmaceutical grade, selective bispecific compound in clinical development that clearly and novelly targets in a single molecule the Sigma-1 receptor with unambiguous antagonist activity and the Mu-opioid receptor with partial agonist activity.
RECENT SCIENTIFIC PUBLICATIONS RELATED TO SIGMA RECEPTORS AND NEUROPATHIC PAIN
Highly specific σ2R/TMEM97 ligand FEM-1689 alleviates neuropathic pain and inhibits the integrated stress response
By Muhammad Saad Yousuf, James J. Sahn, Hongfen Yang, Eric T. David, Stephanie Shiers, Marisol Mancilla Moreno, Jonathan Iketem, Danielle M. Royer, Chelsea D. Garcia, Jennifer Zhang, Veronica M. Hong, Subhaan M. Mian, Ayesha Ahmad, Benedict J. Kolber, Daniel J. Liebl, Stephen F. Martin, and Theodore J. Price Excerpt from the article published in Proceedings […]
A Practical Guide to Sigma-1 Receptor Positron Emission Tomography/Magnetic Resonance Imaging: A New Clinical Molecular Imaging Method to Identify Peripheral Pain Generators in Patients with Chronic Pain
By Bin Shen, Daehyun Yoon, Jessa Castillo, and Sandip Biswal Excerpt from the article published in Semin Musculoskelet Radiol, November 2023; 27(06): 601-617 DOI: 10.1055/s-0043-1775744 Editor’s Highlights Abstract Accurately identifying the peripheral pain generator in patients with chronic pain remains a major challenge for modern medicine. Millions of patients around the world suffer endlessly from […]
Sigma-1 Receptor Inhibition Reduces Mechanical Allodynia and Modulate Neuroinflammation in Chronic Neuropathic Pain
By Simona Denaro, Lorella Pasquinucci, Rita Turnaturi, Cristiana Alberghina, Lucia Longhitano, Sebastiano Giallongo, Giuliana Costanzo, Salvatore Spoto, Margherita Grasso, Agata Zappalà, Giovanni Li Volti, Daniele Tibullo, Nunzio Vicario, Rosalba Parenti, and Carmela Parenti Excerpt from the article published in Mol Neurobiol (November 3, 2023). DOI: https://doi.org/10.1007/s12035-023-03717-w Editor’s Highlights Abstract Neuropathic pain is one of the most […]
Sigma1 Regulates Lipid Droplet–Mediated Redox Homeostasis Required for Prostate Cancer Proliferation
By Halley M. Oyer; Alexandra R. Steck; Charles G. Longen; Sanjana Venkat; Konuralp Bayrak; Eleanor B. Munger; Dan Fu; Paola A. Castagnino; Christina M. Sanders; Nathalia A. Tancler; My T. Mai; Justin P. Myers; Matthew J. Schiewer; Nan Chen; Elahe A. Mostaghel; and Felix J. Kim Excerpt from the article published in Cancer Research Communications (October […]
Genetic and Pharmacological Blockade of Sigma-1 Receptors Attenuates Inflammation-Associated Hypersensitivity during Acute Colitis in CD1 Mice
By Sergio López-Estévez, Mònica Aguilera, Georgia Gris, Beatriz de la Puente, Alicia Carceller, and Vicente Martínez Excerpt from the article published in Biomedicines. 12 October 2023; 11(10):2758. DOI: https://doi.org/10.3390/biomedicines11102758 Editor’s Highlights Abstract Sigma-1 receptors (σ1Rs) are implicated in nociception, including pain sensitization, and inflammation. We assessed the role of σ1Rs on acute colitis-associated hypersensitivity using […]
Sigma-1 receptor agonism exacerbates immune-driven nociception: Role of TRPV1 + nociceptors
By M. Carmen Ruiz-Cantero, Miguel Á. Huerta, Miguel Á. Tejada, Miriam Santos-Caballero, Eduardo Fernández-Segura, Francisco J. Cañizares, José M. Entrena, José M. Baeyens, and Enrique J. Cobos Excerpt from the article published in Biomedicine & Pharmacotherapy, Volume 167, November 2023, 115534, ISSN 0753-3322, DOI: https://doi.org/10.1016/j.biopha.2023.115534. Highlights Abstract The analgesic effects of sigma-1 antagonists are undisputed, but the […]
Sigma-1 receptor expression in a subpopulation of lumbar spinal cord microglia in response to peripheral nerve injury
By Ethan Schonfeld, Thomas Michael Johnstone, Ghani Haider, Aaryan Shah, Neelan Joseph Marianayagam, Sandip Biswal, and Anand Veeravagu Excerpt from the article published in Scientific Reports 13, 14762 (07 September 2023). DOI: https://doi.org/10.1038/s41598-023-42063-8 Editor’s Highlights Abstract Sigma-1 Receptor has been shown to localize to sites of peripheral nerve injury and back pain. Radioligand probes have been […]
The Emerging Role of Sigma Receptors in Pain Medicine
By Joseph Pergolizzi Jr and Giustino Varrassi Excerpt from the article published in Cureus 15(7): e42626. July 28, 2023, doi:10.7759/cureus.42626 Abstract Sigma receptors are protein chaperones with the unexpected characteristic of being activated by ligand binding. As such, they represent intriguing new targets for potential drug development. As a protein chaperone, these “receptors” escort proteins from […]
Validation of σ2R/TMEM97 as a neuropathic pain target: Specificity, human expression and mechanism of action
By Muhammad Saad Yousuf, James J. Sahn, Eric T. David, Stephanie Shiers, Danielle M. Royer, Chelsea D. Garcia, Jennifer Zhang, Veronica M. Hong, Ayesha Ahmad, Benedict J. Kolber, Daniel J Liebl, Stephen F. Martin, and Theodore J. Price Excerpt from the article published in bioRxiv 2023.04.11., 536439; DOI: https://doi.org/10.1101/2023.04.11.536439 Editor’s Highlights Abstract The Sigma 2 receptor (σ2R) […]
TRPA1 modulation by Sigma-1 receptor prevents oxaliplatin-induced painful peripheral neuropathy
By Aida Marcotti, Jorge Fernández-Trillo, Alejandro González, Marta Vizcaíno-Escoto, Pablo Ros-Arlanzón, Luz Romero, José Miguel Vela, Ana Gomis, Félix Viana, and Elvira de la Peña Excerpt from the article published in Brain, Volume 146, Issue 2, February 2023, Pages 475–491, DOI: https://doi.org/10.1093/brain/awac273 Editor’s Highlights Abstract Chemotherapy-induced peripheral neuropathy is a frequent, disabling side effect of anticancer […]
αN-Acetyl β-Endorphin Is an Endogenous Ligand of σ1Rs That Regulates Mu-Opioid Receptor Signaling by Exchanging G Proteins for σ2Rs in σ1R Oligomers
By Javier Garzón-Niño, Elsa Cortés-Montero, María Rodríguez-Muñoz, and Pilar Sánchez-Blázquez Excerpt from the article published in the International Journal of Molecular Sciences. 2023; 24(1):582, 29 December 2022, DOI: https://doi.org/10.3390/ijms24010582 Editor’s Highlights Abstract The opioid peptide β-endorphin coexists in the pituitary and brain in its αN-acetylated form, which does not bind to opioid receptors. We now report […]
Hevin/Sparcl1 drives pathological pain through spinal cord astrocyte and NMDA receptor signaling
By Gang Chen, Jing Xu, Hao Luo, Xin Luo, Sandeep K. Singh, Juan J. Ramirez, Michael L. James, Joseph P. Mathew, Miles Berger, Cagla Eroglu, and Ru-Rong Ji Excerpt from the article published in JCI Insight, Volume 7, Issue 23 on December 8, 2022, e161028. DOI: https://doi.org/10.1172/jci.insight.161028. Editor’s Highlights Abstract High endothelial venule protein/SPARC-like 1 […]
The sigma-1 receptor curtails endogenous opioid analgesia during sensitization of TRPV1 nociceptors
By M. Carmen Ruiz-Cantero, Elsa Cortés-Montero, Aakanksha Jain, Ángeles Montilla-García, Inmaculada Bravo-Caparrós, Jaehoon Shim, Pilar Sánchez-Blázquez, Clifford J. Woolf, José M. Baeyens, and Enrique J. Cobos Excerpt from the article published in British Journal of Pharmacology, 1– 20, 07 December 2022, DOI: https://doi.org/10.1111/bph.16003 Editor’s Highlights Abstract Background and Purpose: Peripheral sensitization contributes to pathological pain. While prostaglandin […]
Sigma Antagonists for Treatment of Neuropathic Pain Syndromes in Cancer Patients: A Narrative Review
By Joseph V. Pergolizzi, Jr. and Jo Ann LeQuang Article published in Journal of Cancer Research Updates, 11, 70–77, 2022-10-27, DOI: https://doi.org/10.30683/1929-2279.2022.11.10 Abstract Almost 40% of cancer patients have neuropathic pain or mixed pain with a neuropathic component, which can be intense, debilitating, and challenging to treat. New studies on sigma receptors show these enigmatic ligand-binding […]
Bispecific sigma-1 receptor antagonism and mu-opioid receptor partial agonism: WLB-73502, an analgesic with improved efficacy and safety profile compared to strong opioids
By Alba Vidal-Torres, Begoña Fernández-Pastor, Mónica García, Eva Ayet, Anna Cabot, Javier Burgueño, Xavier Monroy, Bertrand Aubel, Xavier Codony, Luz Romero, Rosalía Pascual, Maria Teresa Serafini, Gregorio Encina, Carmen Almansa, Daniel Zamanillo, Manuel Merlos, and José Miguel Vela Excerpt from the article published in Acta Pharmaceutica Sinica B, September 25, 2022, ISSN 2211-3835, DOI: https://doi.org/10.1016/j.apsb.2022.09.018 […]
Characterization of CM-398, a Novel Selective Sigma-2 Receptor Ligand, as a Potential Therapeutic for Neuropathic Pain
By Lisa L. Wilson, Amy R. Alleyne, Shainnel O. Eans, Thomas J. Cirino, Heather M. Stacy, Marco Mottinelli, Sebastiano Intagliata, Christopher R. McCurdy, and Jay P. McLaughlin Excerpt from the article published in Molecules 2022, 27(11), 3617; DOI: https://doi.org/10.3390/molecules27113617 Editor’s Highlights First identified as Tmem97, the sigma-2 receptor (S2R) was only recently cloned in 2017 and is known […]
Pharmacologic Management of Persistent Pain in Cancer Survivors
by Glare, P., Aubrey, K., Gulati, A. et al. Excerpt from the article published in Drugs (2022). https://doi.org/10.1007/s40265-022-01675-6 Editor’s Highlights Abstract Improvements in screening, diagnosis and treatment of cancer has seen cancer mortality substantially diminish in the past three decades. It is estimated there are almost 20 million cancer survivors in the USA alone, but some 40% […]
Sigma-1 receptor increases intracellular calcium in cultured astrocytes and contributes to mechanical allodynia in a model of neuropathic pain
By Jae-Gyun Choi, Sheu-Ran Choi, Dong-Wook Kang, Jaehyuk Kima, Jin Bong Park, Jang-Hern Lee, and Hyun-Woo Kim Introduction to the article published in Brain Research Bulletin, Volume 178, January 2022, Pages 69-81 DOI: https://doi.org/10.1016/j.brainresbull.2021.11.010 Autors’ Highlights Abstract Recent studies have revealed that glial sigma-1 receptor (Sig-1R) in the spinal cord may be a critical factor […]
Sigma-1 receptors and progesterone metabolizing enzymes in nociceptive sensory neurons of the female rat trigeminal ganglia: A neural substrate for the antinociceptive actions of progesterone
By Rebecca S. Hornung, Namrata GR Raut, Daisy J. Cantu, Lauren M Lockhart, and Dayna L. Averitt Excerpt from the article published in Molecular Pain. January 2022. DOI: 10.1177/17448069211069255 Editor’s Highlights Pain signaled by the trigeminal nociceptors is common, often debilitating, and includes musculoskeletal, neurovascular, and neuropathic pain Trigeminal sensory neurons are an anatomical substrate for the […]
Examination of the Novel Sigma-1 Receptor Antagonist, SI 1/28, for Antinociceptive and Anti-allodynic Efficacy against Multiple Types of Nociception with Fewer Liabilities of Use
By Lisa L. Wilson, Shainnel O. Eans, Insitar Ramadan-Siraj, Maria N. Modica, Giuseppe Romeo, Sebastiano Intagliata,and Jay P. McLaughlin Excerpt from the article published in International Journal of Molecular Sciences 23, no. 2: 615. Published: 6 January 2022, DOI: https://doi.org/10.3390/ijms23020615 Editor’s Highlights Chronic neuropathic pain is a common cause of decreased quality of life and disability […]
The Sigma-1 Receptor and the HINT1 Protein Control Alpha2Delta-1 Binding to Glutamate NMDA Receptors: Implications in Neuropathic Pain
by Rodríguez-Muñoz M, Cortés-Montero E, Onetti Y, Sánchez-Blázquez P, Garzón-Niño J. Excerpt from the article published in Biomolecules. 2021 Nov 12;11(11):1681. doi: 10.3390/biom11111681. PMID: 34827679; PMCID: PMC8615847. Editor’s Highlights Abstract Nerve injury produces neuropathic pain through the binding of α2δ1 proteins to glutamate N-methyl-D-aspartate receptors (NMDARs). Notably, mice with a targeted deletion of the sigma 1 […]
Targeting strategies for oxaliplatin-induced peripheral neuropathy: clinical syndrome, molecular basis, and drug development
By Yang Yang, Bing Zhao, Xuejiao Gao, Jinbing Sun, Juan Ye, Jun Li, and Peng Cao Excerpt from the article published in Journal of Experimental & Clinical Cancer Research volume 40, Article number: 331 (2021), Published: 22 October 2021, DOI: https://doi.org/10.1186/s13046-021-02141-z Editor’s Highlights Chemotherapy-induced peripheral neuropathy (CIPN) is a serious clinical problem caused by cytotoxic drugs that cause different pathologic insults to […]
Intrathecal interleukin-1β decreases sigma-1 receptor expression in spinal astrocytes in a murine model of neuropathic pain
By Sheu-Ran Choi, Ho Jae Han, Alvin J. Beitz, and Jang-Hern Lee Excerpt from the article published in Biomedicine & Pharmacotherapy, Volume 144, December 2021, 112272, ISSN 0753-3322, published online October 1, 2021, DOI: https://doi.org/10.1016/j.biopha.2021.112272. Editor’s Highlights Autors’ Highlights Abstract The sigma-1 receptor (Sig-1R) plays an important role in spinal pain transmission by increasing phosphorylation of the N-methyl-D-aspartate […]
Bifunctional μ opioid and σ1 receptor ligands as novel analgesics with reduced side effects
By Tao Zhuang, Jiaying Xiong, Shuaishuai Hao, Wei Du, Zhenming Liu, Bifeng Liu, Guisen Zhang, and Yin Chen Introduction to the article published in European Journal of Medicinal Chemistry, Volume 223, 2021. Doi: https://doi.org/10.1016/j.ejmech.2021.113658 Editor’s Highlights Pain is undoubtedly both a major clinical and economic problem, affecting approximately 20% of the adult population worldwide. There […]
Nociceptive TRP Channels and Sex Steroids
By Óscar Enciso-Pablo, Karina Angélica Méndez-Reséndiz, Tamara Rosenbaum, and Sara Luz Morales-Lázaro Excerpt from the article published in Reproductive Hormones, edited by Courtney Marsh. London: IntechOpen, March 24th, 2021. DOI: 10.5772/intechopen.95552 Editor’s Highlights Several experiments made in pain animal models have demonstrated the existence of sexual dimorphism in response to pain. Rats from a diabetic […]
Genomic Action of Sigma-1 Receptor Chaperone Relates to Neuropathic Pain
By Shao-Ming Wang, Nino Goguadze, Yuriko Kimura, Yuko Yasui, Bin Pan, Tzu-Yun Wang, Yoki Nakamura, Yu-Ting Lin, Quinn H. Hogan, Katherine L. Wilson, Tsung-Ping Su, and Hsiang-en Wu Excerpt from the article published in Molecular Neurobiology volume 58, pages 2523–2541 (2021) DOI: https://doi.org/10.1007/s12035-020-02276-8 Editor’s Highlights Neuropathic pain is one of the most debilitating forms of […]
Spinal mechanisms contributing to the development of pain hypersensitivity induced by sphingolipids in the rat
By Hong Wei, Zuyue Chen, Ari Koivisto, and Antti Pertovaara Excerpt from the article published in Pharmacological Reports 73, 672–679 (2021). 03 January 2021 DOI: https://doi.org/10.1007/s43440-020-00207-x Editor’s Highlights Dysregulation of sphingolipid metabolism has been associated with pathophysiological pain conditions. Among spinal receptors that sphingolipids, including DMS, can activate is the transient receptor potential melastatin-3 channel (TRPM3). In […]
Calmodulin Supports TRPA1 Channel Association with Opioid Receptors and Glutamate NMDA Receptors in the Nervous Tissue
By Elsa Cortés-Montero, María Rodríguez-Muñoz, M. Carmen Ruiz-Cantero, Enrique J. Cobos, Pilar Sánchez-Blázquez, and Javier Garzón-Niño Excerpt from the article published in International Journal of Molecular Sciences 22, no. 1: 229. Published: 28 December 2020, DOI: https://doi.org/10.3390/ijms22010229 Editor’s Highlights TRPA1 is the only mammalian member of the transient receptor potential (TRP) ankyrin channel subfamily. There is […]
The Sigma 2 receptor promotes and the Sigma 1 receptor inhibits mu-opioid receptor-mediated antinociception
By Sánchez-Blázquez, P., Cortés-Montero, E., Rodríguez-Muñoz, M. et al. Excerpt from the article published in Mol Brain 13, 150 (2020). https://doi.org/10.1186/s13041-020-00676-4 Editor’s Highlights σ2R is essential for the antinociceptive effects of exogenous and endogenous ligands of MOR but not for the antinociceptive effects of other families of G-receptors that also mediate analgesia, such as DOR, CB1R and α2AR. […]
Role of transient receptor potential ankyrin 1 (TRPA1) on nociception caused by a murine model of breast carcinoma
By Amanda Spring de Almeida, Flávia Karine Rigo, Samira Dal-Toé De Prá, Alessandra Marcone Milioli, Gabriele Cheiran Pereira, Débora Denardin Lückemeyer, Caren Tatiane Antoniazzi, Sabrina Qader Kudsi, Daniel Mendes Pereira Ardisson Araújo, Sara Marchesan Oliveira, Juliano Ferreira, and Gabriela Trevisan Excerpt from the article published in Pharmacological Research, Volume 152, February 2020, 104576, ISSN 1043-6618, […]
Ligands Exert Biased Activity to Regulate Sigma 1 Receptor Interactions With Cationic TRPA1, TRPV1, and TRPM8 Channels
By Elsa Cortés-Montero, Pilar Sánchez-Blázquez, Yara Onetti, Manuel Merlos and Javier Garzón Excerpt from the article published in Frontiers in Pharmacology, 2019 volume 10 DOI=10.3389/fphar.2019.00634 Editor’s Highlights The sigma 1 receptor (σ1R) and the mu-opioid receptor (MOR) regulate the transient receptor potential (TRP) V1 calcium channel. TRP ankyrin member 1 (TRPA1) receptors are coexpressed with TRPV1 […]
TRPV1 channels and the progesterone receptor Sig-1R interact to regulate pain
By Miguel Ortíz-Rentería, Rebeca Juárez-Contreras, Ricardo González-Ramírez, and Sara L. Morales-Lázaro Excerpt from the article published in PNAS, January 29, 2018, 115 (7) E1657-E1666, DOI: https://doi.org/10.1073/pnas.1715972115 Significance The TRPV1 ion channel has been widely associated with the generation of painful responses. The responses of cells expressing this ion channel and, presumably, the overall pain response of an […]
Sigma 2 Receptor/Tmem97 Agonists Produce Long Lasting Antineuropathic Pain Effects in Mice
By James J Sahn, Galo L Mejia, Pradipta R Ray, Stephen F Martin, and Theodore J Price Excerpt from the article published in ACS chemical neuroscience, 2017 Aug 16;8(8):1801-1811. DOI: https://doi.org/10.1021/acschemneuro.7b00200 Free PMC article Editor’s Highlights Abstract Neuropathic pain is an important medical problem with few effective treatments. The sigma 1 receptor (σ1R) is known to be […]