Article
Plant Sciences
Donya Ziafatdoost Abed, Reyhaneh Sadeghian, Saeed Mohammadi, Muhammad Akram
Summary: The essential oil of Thymus persicus showed strong antinociceptive and anti-neuropathic effects in Swiss mice, involving various signaling pathways and receptors.
JOURNAL OF ETHNOPHARMACOLOGY
(2022)
Article
Medicine, Research & Experimental
Sergio Lopez-Estevez, Georgia Gris, Beatriz de la Puente, Alicia Carceller, Vicente Martinez
Summary: Sigma-1 receptors play an important role in intestinal inflammation-associated referred hyperalgesia, with knockout mice showing significant attenuation in inflammation associated hypersensitivity. The absence of sigma(1)Rs had little impact on colitis generation and progression, but did show reduction in edema and down-regulation of iNOS gene expression during the chronic phase.
BIOMEDICINE & PHARMACOTHERAPY
(2021)
Article
Chemistry, Medicinal
Zulkifal Malik, Muzaffar Abbas, Lina Tariq Al Kury, Fawad Ali Shah, Mahboob Alam, Arif-ullah Khan, Humaira Nadeem, Saad Alghamdi, Muhammad Umar Khayam Sahibzada, Shupeng Li
Summary: The study investigated the effects of thiazolidine derivatives 1b and 1d on inflammatory pain in mice. The compounds attenuated carrageenan-induced thermal hyperalgesia and mechanical allodynia, reduced IL-1 beta expression in the spinal cord, and were found to be safe with no motor coordination deficits.
DRUG DESIGN DEVELOPMENT AND THERAPY
(2021)
Article
Pharmacology & Pharmacy
Hichem Bouchenaki, Aurore Danigo, Amandine Bernard, Flavien Bessaguet, Laurence Richard, Franck Sturtz, David Balayssac, Laurent Magy, Claire Demiot
Summary: The study evaluated the effect of the ACE inhibitor ramipril in a mouse model of oxaliplatin-induced acute pain syndrome, showing that ramipril can prevent cold sensitivity and improve tactile sensitivity in treated mice.
FRONTIERS IN PHARMACOLOGY
(2021)
Article
Immunology
Andrew D. Gaudet, Laura K. Fonken, Monica T. Ayala, Steven F. Maier, Linda R. Watkins
Summary: Aging increases susceptibility to pain and death after SCI in mice, while deletion of miR-155 reduces pain symptoms and mortality. Aging mice exhibit heightened heat sensitivity and evoked pain symptoms, highlighting the importance of studying geriatric models of SCI.
BRAIN BEHAVIOR AND IMMUNITY
(2021)
Article
Anesthesiology
Polina Shabes, Daniela C. Rosenberger, Florian Henrich, Wolfgang Greffrath, Rolf-Detlef Treede, Ulf Baumgaertner, Walter Magerl
Summary: In this study, acute sensitization of the skin with topical capsaicin was found to enhance the sustained phase of pain in a noninvasive surrogate model of intraoperative pain. Capsaicin increased the pain magnitude and duration induced by the blade, but did not fully match the sustained duration of incisional pain. The blade model showed similarities to incisional pain in normal skin and acquired a more capsaicin-like pain descriptor pattern in capsaicin-treated skin, possibly due to peripheral sensitization of the TRPV1 receptor.
Article
Behavioral Sciences
Guadalupe Garcia, Vladimir A. Martinez-Rojas, Janet Murbartian
Summary: TREK-1 channels play a crucial role in acute and persistent nociceptive hypersensitivity, with selective blockade or activation affecting pain behaviors. The activity of TREK-1 at peripheral and spinal sites can reduce neuronal excitability in a formalin-induced nociception model.
BEHAVIOURAL BRAIN RESEARCH
(2021)
Article
Pharmacology & Pharmacy
Neha Munawar, Joelle Nader, Najat H. Khadadah, Ashraf Al Madhoun, Waleed Al-Ali, Linu A. Varghese, Willias Masocha, Fahd Al-Mulla, Milad S. Bitar
Summary: This study found that alpha-2A adrenoceptors (alpha 2-AR) in the nervous system of streptozotocin diabetic rats are upregulated, and the upregulation is associated with increased pain sensitivity. Chronic administration of the selective alpha 2-AR agonist guanfacine can downregulate the upregulation of alpha 2-AR and relieve hyperalgesia and allodynia in diabetic animals. These findings suggest that guanfacine may have potential as a potent analgesic for diabetic neuropathic pain.
Article
Cell Biology
Huixing Wang, Xiaodong Huo, Chenyang Han, Jiang Ning, Hongguang Chen, Bo Li, Jingzhi Liu, Wenting Ma, Quanbo Li, Yonghao Yu, Kemei Shi
Summary: The study in rats indicated that ferroptosis is involved in the development of neuropathic pain by blocking neuron and astrocyte activation in the spinal dorsal horn.
MOLECULAR AND CELLULAR BIOCHEMISTRY
(2021)
Article
Biochemistry & Molecular Biology
Giada Amodeo, Silvia Franchi, Giulia Galimberti, Laura Comi, Simona D'Agnelli, Marco Baciarello, Elena Giovanna Bignami, Paola Sacerdote
Summary: Knee osteoarthritis is a common cause of pain and disability in old subjects. Pain may lead to the development of frailty. This study used a mice model and found that older mice are more vulnerable to the detrimental effects of pain, but treatment with morphine can mitigate these effects.
Article
Biochemistry & Molecular Biology
Neha Munawar, Milad S. Bitar, Willias Masocha
Summary: This study investigates the role of serotoninergic nervous system in diabetic neuropathic pain (DNP) and suggests that treatment with 8-OH-DPAT, a selective 5-HT1AR agonist, could be effective in alleviating DNP symptoms.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2023)
Article
Biochemistry & Molecular Biology
Santiago Coral-Perez, Ignacio Martinez-Martel, Maria Martinez-Serrat, Gerard Batalle, Xue Bai, Christie R. A. Leite-Panissi, Olga Pol
Summary: The study demonstrates the potential therapeutic application of molecular hydrogen-rich water (HRW) in chronic inflammatory pain and associated comorbidities, showing its analgesic, antidepressant, and anxiolytic actions, as well as its protective, anti-inflammatory, and antioxidant qualities.
Article
Anesthesiology
Tobias Schneider, Laura Zurbriggen, Markus Dieterle, Eckhard Mauermann, Priska Frei, Katja Mercer-Chalmers-Bender, Wilhelm Ruppen
Summary: This study assessed the effect of cannabidiol (CBD) on acute pain and found that oral administration of 800 mg CBD did not show a significant effect on pain intensity, hyperalgesia, and allodynia compared with placebo. The study suggests the need for further research on different dosing, routes of administration, and the use of CBD as part of multimodal treatment strategies.
Review
Clinical Neurology
Zhen-Rong Zhang, Yao Wu, Wen-Jing Wang, Fang-Yong Wang
Summary: The role of GABAergic cell transplantation in improving neuropathic pain is significant, showing statistically significant improvements in allodynia and hyperalgesia. Differentiated GABAergic cells and avoiding the use of antibiotics may have a better effect in improving neuropathic pain.
FRONTIERS IN NEUROLOGY
(2022)
Article
Biochemistry & Molecular Biology
Baiba Svalbe, Baiba Zvejniece, Gundega Stelfa, Karlis Vilks, Edijs Vavers, Jose Miguel Vela, Maija Dambrova, Liga Zvejniece
Summary: This study found that the absence of Sig1R significantly influenced metabolic pathways such as amino acids, sphingolipids, and serotonin. Sig1R KO mice had higher levels of serotonin and histamine in their blood and brain tissues, which were correlated with behavioral changes.
Article
Biochemistry & Molecular Biology
Leandro Ruiz-Leyva, Ana Vazquez-Agredos, Ana M. Jimenez-Garcia, Olga Lopez-Guarnido, Antonio Pla, Ricardo Marcos Pautassi, Ignacio Moron Henche, Cruz Miguel Cendan
Summary: The present study validates a novel model of voluntary ethanol consumption in male Wistar rats, in which ethanol access follows binge eating, and demonstrates a significant increase in ethanol consumption after binge eating compared to control eating. This model shows remarkable potential for research on different stages of alcohol addiction and assessing interactions between alcohol consumption and other addictive-like behaviors.
Article
Chemistry, Medicinal
Elena Bechthold, Julian A. Schreiber, Nadine Ritter, Lucie Grey, Dirk Schepmann, Constantin Daniliuc, Rafael Gonzalez-Cano, Francisco Rafael Nieto, Guiscard Seebohm, Bernhard Wuensch
Summary: This study synthesized several high affinity sigma(1) ligands by replacing the piperidine ring and introducing a bicyclic tropane system. Two of these compounds showed high antiallodynic activity in vivo and exhibited high selectivity for the sigma(1) receptor.
EUROPEAN JOURNAL OF MEDICINAL CHEMISTRY
(2022)
Article
Neurosciences
Agustin Salguero, Leonardo Marengo, Enrique Portillo-Salido, Leandro Ruiz-Leyva, Cruz Miguel Cendan, Ignacio Moron Henche, Ricardo Marcos Pautassi
Summary: The study explored the effects of sigma-1 receptors (S1-R) activation on ethanol-induced conditioned taste aversion (CTA) in early adolescence and terminal adolescence/emerging adulthood in female Wistar rats. The results showed that S1-R activation attenuated the learning of ethanol-induced CTA at terminal adolescence but not at early adolescence. Additionally, S1-R activation did not significantly affect binge-like ethanol intake in terminal adolescents.
NEUROSCIENCE LETTERS
(2022)
Article
Clinical Neurology
Teresa Vezza, Jose Alberto Molina-Tijeras, Rafael Gonzalez-Cano, Alba Rodriguez-Nogales, Federico Garcia, Julio Galvez, Enrique J. Cobos
Summary: Abdominal pain is a common symptom in patients with inflammatory bowel disease (IBD) and has a significant impact on their quality of life. Minocycline, a broad-spectrum tetracycline antibiotic, has been identified as a potential therapy for managing visceral pain in IBD-induced colitis in mice.
Article
Clinical Neurology
Juan-Fernando Padin, Marcos Maroto, Jose Manuel Entrena, Javier Egea, Eulalia Montell, Josep Verges, Manuela G. Lopez, Enrique J. Cobos, Antonio G. Garcia
Summary: A new sulfated disaccharide compound, BIS014, has been found to have analgesic effects and can alleviate various neuropathic pain conditions. Unlike existing drugs, BIS014 does not cause sedation and has the potential to become a new effective non-sedative oral medication for neuropathic pain treatment.
Article
Pharmacology & Pharmacy
M. Carmen Ruiz-Cantero, Elsa Cortes-Montero, Aakanksha Jain, Angeles Montilla-Garcia, Inmaculada Bravo-Caparros, Jaehoon Shim, Pilar Sanchez-Blazquez, Clifford J. Woolf, Jose M. Baeyens, Enrique J. Cobos
Summary: The sigma-1 receptor interacts with TRPV1 and the μ-opioid receptor, and antagonizing sigma-1 receptor can reduce PGE2- and NGF-induced hyperalgesia by increasing the activity of the μ-opioid receptor. This mechanism is not effective against GDNF-induced hyperalgesia. The sigma-1 antagonism transfers the sigma-1 receptor from TRPV1 to μ-opioid receptor and harnesses endogenous opioids produced by TRPV1+ neurons to reduce hyperalgesia.
BRITISH JOURNAL OF PHARMACOLOGY
(2023)
Article
Biochemistry & Molecular Biology
Maria Dichiara, Francesca Alessandra Ambrosio, Carla Barbaraci, Rafael Gonzalez-Cano, Giosue Costa, Carmela Parenti, Agostino Marrazzo, Lorella Pasquinucci, Enrique J. Cobos, Stefano Alcaro, Emanuele Amata
Summary: The development of diazabicyclo[4.3.0]nonane and 2,7-diazaspiro[3.5]nonane derivatives as sigma receptors (SRs) ligands is discussed. The compounds were evaluated for their binding to S1R and S2R, and modeling studies were conducted to analyze the binding mode. Three notable compounds, 4b, 5b, and 8f, were further tested for their analgesic effects and functional profiles. Compound 4b showed S1R agonistic effects, while compounds 5b and 8f exhibited S1R antagonism.
ACS CHEMICAL NEUROSCIENCE
(2023)
Article
Chemistry, Medicinal
Luca Blicker, Rafael Gonzalez-Cano, Erik Laurini, Francisco R. Nieto, Judith Schmidt, Dirk Schepmann, Sabrina Pricl, Bernhard Wunsch
Summary: Antagonists targeting sigma 1 receptors show promise for neuropathic pain treatment. A series of aminodiols were synthesized from (-)-isopulegol (1) and transformed into bicyclic and tricyclic derivatives. The aminodiols exhibited higher sigma 1 affinity compared to the derivatives. The study also revealed the importance of stereochemistry and compound structure in modulating sigma 1 affinity.
JOURNAL OF MEDICINAL CHEMISTRY
(2023)
Review
Chemistry, Medicinal
Miguel A. Huerta, Javier de la Nava, Antonia Artacho-Cordon, Francisco R. Nieto
Summary: The current pharmacological treatment for cancer-related pain is not satisfactory. This study conducted a systematic review and meta-analysis to evaluate the clinical evidence of tetrodotoxin (TTX) in treating cancer-related pain. The results showed that TTX significantly increased the number of responders to treatment and the occurrence of non-severe adverse events.
Article
Chemistry, Medicinal
Maria Dichiara, Francesca Alessandra Ambrosio, Sang Min Lee, M. Carmen Ruiz-Cantero, Jessica Lombino, Adriana Coricello, Giosue Costa, Dhara Shah, Giuliana Costanzo, Lorella Pasquinucci, Kyung No Son, Giuseppe Cosentino, Rafael Gonzalez-Cano, Agostino Marrazzo, Vinay Kumar Aakalu, Enrique J. Cobos, Stefano Alcaro, Emanuele Amata
Summary: This work focuses on the design and synthesis of 2,7-diazaspiro[4.4]nonane derivatives as potent sigma receptor (SR) ligands with analgesic activity. The affinities of the compounds at S1R and S2R were measured, and molecular modeling studies were conducted to investigate the binding characteristics. The most promising compound 9d (AD258) showed negligible in vitro cellular toxicity, high binding affinity to both SRs, and high potency in a capsaicin-induced allodynia model.
JOURNAL OF MEDICINAL CHEMISTRY
(2023)
Article
Chemistry, Medicinal
Katarzyna Szczepanska, Tadeusz Karcz, Maria Dichiara, Szczepan Mogilski, Justyna Kalinowska-Tluscik, Boguslaw Pilarski, Arkadiusz Leniak, Wojciech Pietrus, Sabina Podlewska, Katarzyna Popiolek-Barczyk, Laura J. Humphrys, M. Carmen Ruiz-Cantero, David Reiner-Link, Luisa Leitzbach, Dorota Lazewska, Steffen Pockes, Michal Gorka, Adam Zmyslowski, Thierry Calmels, Enrique J. Cobos, Agostino Marrazzo, Holger Stark, Andrzej J. Bojarski, Emanuele Amata, Katarzyna Kiec-Kononowicz
Summary: In search of new dual-acting histamine H-3/sigma-1 receptor ligands, a series of compounds were designed based on previously studied highly active in vivo ligands. An in-depth analysis was conducted on the protonation states of piperazine and piperidine derivatives in the compounds, due to the significant difference in affinity at sigma-1 receptors observed in closely related compounds. Three lead structures (3, 7, and 12) were selected for further biological evaluation, and compound 12 showed a broad spectrum of analgesic activity based on a novel molecular mechanism in both nociceptive and neuropathic pain models.
JOURNAL OF MEDICINAL CHEMISTRY
(2023)
Article
Chemistry, Medicinal
Luca Blicker, Rafael Gonzalez-Cano, Erik Laurini, Francisco R. Nieto, Judith Schmidt, Dirk Schepmann, Sabrina Pricl, Bernhard Wuensch
Summary: Antagonists at a1 receptors have great potential for treating neuropathic pain. The study examined different compounds and found that amino-diols showed higher a1 affinity than bicyclic and tricyclic derivatives. The configuration and structure of the compounds also influenced their a1 affinity and selectivity. A specific compound, aminodiol 8b, demonstrated high a1 affinity, selectivity, and promising activity in pain relief.
JOURNAL OF MEDICINAL CHEMISTRY
(2023)
Article
Chemistry, Medicinal
Sandra Codony, Jose M. Entrena, Carla Calvo-Tusell, Beatrice Jora, Rafael Gonzalez-Cano, Silvia Osuna, Ruben Corpas, Christophe Morisseau, Belen Perez, Marta Barniol-Xicota, Christian Grinan-Ferre, Concepcion Perez, Maria Isabel Rodriguez-Franco, Anton L. Martinez, M. Isabel Loza, Merce Pallas, Steven H. L. Verhelst, Coral Sanfeliu, Ferran Feixas, Bruce D. Hammock, Jose Brea, Enrique J. Cobos, Santiago Vazquez
Summary: A new benzohomoadamantane-based sEH inhibitor has been developed to improve the drug metabolism and pharmacokinetics properties for pain-related disorders, showing anti-allodynic and analgesic effects in murine models of capsaicin-induced allodynia and cyclophosphamide-induced cystitis.
JOURNAL OF MEDICINAL CHEMISTRY
(2022)
Article
Pharmacology & Pharmacy
Laura Cabeza, Mazen M. El-Hammadi, Raul Ortiz, Maria D. Cayero-Otero, Julia Jimenez-Lopez, Gloria Perazzoli, Lucia Martin-Banderas, Jose M. Baeyens, Consolacion Melguizo, Jose Prados
Summary: The study demonstrated that PTX-PLGA nanoparticles significantly reduced the IC50 of breast cancer cells to paclitaxel, showing higher antitumor activity in vivo. The nanoformulation preserved the mechanism of action of paclitaxel and increased its intracellular uptake.