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
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
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)
Review
Biochemistry & Molecular Biology
Andrea Bortolin, Estrela Neto, Meriem Lamghari
Summary: Calcium plays a crucial role in various physiological processes as a signalling mediator. It is involved in pathways that control fast responses like neuronal action potential firing and slow processes like gene transcriptional regulation. In pathological conditions, these mechanisms are also implicated in tumor cell reprogramming and pain regulation. Understanding the interactions between these mechanisms can lead to the identification of new therapeutic targets.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2022)
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
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
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
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
Anesthesiology
Markus Dieterle, Laura Zurbriggen, Eckhard Mauermann, Katja Mercer-Chalmers-Bender, Priska Frei, Wilhelm Ruppen, Tobias Schneider
Summary: This study suggests that a high single-oral dose of 1600 mg cannabidiol is not effective in reducing opioid-induced hyperalgesia (OIH).
Article
Pharmacology & Pharmacy
Myrna Deciga-Campos, Rodrigo Villafan-Gutierrez, Josue Vidal Espinosa-Juarez, Osmar Antonio Jaramillo-Morales, Francisco Javier Lopez-Munoz
Summary: The study found that specific combinations of gabapentin and haloperidol can synergistically reduce nerve injury-induced allodynia and hyperalgesia, demonstrating an antiallodynic and antihyperalgesic effect.
EUROPEAN JOURNAL OF PHARMACOLOGY
(2021)
Article
Dermatology
Sara Moradi Tuchayi, Ying Wang, Alla Khodorova, Isaac J. Pence, Conor L. Evans, R. Rox Anderson, Ethan A. Lerner, Clifford J. Woolf, Lilit Garibyan
Summary: We developed a neural selective and injectable cryoneurolysis method using ice slurry, which effectively reduces cutaneous pain caused by skin disease. This method shows comparable effects on nerve structure and function compared to an FDA-approved cryoneurolysis device. The decrease in mechanical pain from slurry injection, although less profound than that of the FDA-approved device, lasts longer without inducing dysesthesia.
JOURNAL OF INVESTIGATIVE DERMATOLOGY
(2023)
Article
Neurosciences
Ryo Ikeda, Daigo Arimura, Mitsuru Saito
Summary: Knee osteoarthritis impairs daily activities and causes pain, with involvement of mechanical allodynia and hyperalgesia. The role of Piezo channels in mechanically induced pain in osteoarthritis remains unclear, as studies have shown conflicting results regarding its expression levels in affected joints. Further research is needed to understand the mechanisms behind pain sensitization in knee osteoarthritis.
Article
Immunology
Mohammad Mehdi Haghighat Lari, Hamid Reza Banafshe, Elahe Seyed Hosseini, Hamed Haddad Kashani
Summary: In this study, the chronic administration of risperidone was found to be effective in reducing heat hyperalgesia and allodynia in rats with neuropathic pain induced by the CCI model. However, acute administration of risperidone did not show any significant changes in behavioral tests. Gene expression analysis indicated an increase in IL-4 and IL-10 gene expression in the risperidone group compared to the sham group.
INFLAMMOPHARMACOLOGY
(2023)
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
Instruments & Instrumentation
Weizhi Xu, Zonglan Zhao, James Falconer, Andrew K. Whittaker, Amirali Popat, Maree T. Smith, Tushar Kumeria, Felicity Y. Han
Summary: The study found that using a large scCO(2) vessel increased the encapsulation efficiency of ketamine, while pre-loading ketamine into pSi also slightly improved the drug incorporation level. Additionally, the use of a large scCO(2) vessel reduced burst release and extended the release period for PLGA microparticles containing ketamine.
DRUG DELIVERY AND TRANSLATIONAL RESEARCH
(2022)
Article
Behavioral Sciences
Felicity Y. Han, David A. Brockman, Janet R. Nicholson, Laura Corradini, Maree Therese Smith
Summary: Diabetic ketoacidosis (DKA) is a severe complication of diabetes characterized by insulin deficiency and elevated blood glucose levels. It can lead to significant metabolic disturbances and organ damage, including heart muscle, kidney, and neurological impairment, and can even be life-threatening.
BEHAVIOURAL PHARMACOLOGY
(2022)
Article
Chemistry, Medicinal
Maree T. Smith, Dehui Kong, Andy Kuo, Mohammad Z. Imam, Craig M. Williams
Summary: This article discusses the limitations and problems associated with strong opioid analgesics and describes international efforts to discover new and safer opioids. It focuses on medicinal chemistry strategies using structurally diverse compounds derived from natural sources as lead molecules and elaborates on the current research status and approaches in the discovery of novel opioid ligands that retain analgesic effects with improved safety and reduced adverse effects, particularly addiction liability.
JOURNAL OF MEDICINAL CHEMISTRY
(2022)
Article
Chemistry, Multidisciplinary
Minze Zhu, Andrew K. Whittaker, Felicity Y. Han, Maree T. Smith
Summary: Biodegradable polymers have been used as carriers in drug delivery systems for over four decades. They have applications at different scales, from macroscale to nanoscale. These materials have been approved for human use and achieved commercial success. Current research focuses on developing new formulation types for improved drug delivery.
APPLIED SCIENCES-BASEL
(2022)
Article
Instruments & Instrumentation
Weizhi Xu, Faheem Maqbool, Vinod Kumar, James R. Falconer, Cedric S. Cui, Trent M. Woodruff, Karin Borges, Andrew K. Whittaker, Maree T. Smith, Felicity Y. Han
Summary: A sustained-release formulation of ketamine, known as KSL, was developed with high loading and demonstrated prolonged release in mice after intravenous administration. The formulation showed high encapsulation efficiency and drug loading, achieving 100% release in vitro within 8 hours.
DRUG DELIVERY AND TRANSLATIONAL RESEARCH
(2022)
Article
Biochemistry & Molecular Biology
Dehui Kong, Alaa A. Saqer, Matheus Carpinelli de Jesus, Nemat Khan, Alun Jones, Joanne T. Blanchfield, Maree T. Smith, Craig M. Williams
Summary: Multiple sclerosis-associated central neuropathic pain (MS-CNP) is difficult to alleviate and requires novel treatments. A study found that (R)-alpha lipoic acid (ALA) may have pain relief efficacy, but with poor oral bioavailability. By designing and synthesizing biocompatible ester prodrugs of (R)-ALA, a promising candidate (PD-ALA4 HCl salt) was identified.
BIOORGANIC & MEDICINAL CHEMISTRY
(2022)
Article
Pharmacology & Pharmacy
Mohammad Zafar Imam, Andy Kuo, Sussan Ghassabian, Yunxin Cai, Yajuan Qin, Tingyou Li, Maree T. Smith
Summary: CYX-5 is a novel opioid peptide that acts as a G-protein biassed MOP receptor agonist, DOP receptor antagonist, and KOP receptor agonist. It provides pain relief, reduces stool output, and does not cause respiratory depression. The mechanism underlying its constipation effect may involve factors other than beta-arrestin2 recruitment.
PHARMACOLOGICAL REPORTS
(2023)
Review
Oncology
A. E. Smith, A. Muralidharan, M. T. Smith
Summary: Metastatic spread of prostate cancer to the skeleton may result in debilitating bone pain. This review discusses the mechanisms underlying the pathobiology of metastatic prostate cancer induced bone pain and reviews current treatment modalities and pain responses in clinical trials.
Letter
Pharmacology & Pharmacy
Mohammad Zafar Imam, Sussan Ghassabian, Andy Kuo, Yunxin Cai, Yajuan Qin, Tingyou Li, Maree T. Smith
EUROPEAN JOURNAL OF DRUG METABOLISM AND PHARMACOKINETICS
(2023)
Article
Chemistry, Medicinal
Maree T. Smith, Dehui Kong, Andy Kuo, Mohammad Z. Imam, Craig M. Williams
Summary: The opioid crisis has increased the demand for novel opioid analgesics that have superior profiles compared to morphine. This Perspective reviews and discusses the multitargeted opioid ligand strategy for discovering such analgesics. Dual-targeted mu-opioid/delta-opioid (MOP/DOP) ligands with strong DOP antagonist potency and without DOP or kappa-opioid (KOP) agonist activity are promising candidates. Dual-targeted MOP/NOP partial agonists also show potential. The pharmacologic template of cebranopadol, a full agonist at MOP, DOP, and NOP receptors, and a partial agonist at KOP receptor, should be avoided due to its poor therapeutic indices.
JOURNAL OF MEDICINAL CHEMISTRY
(2023)
Review
Immunology
Chen Chen, Maree T. Smith
Summary: Chronic pain is a common health problem that is difficult to adequately treat. Recent research suggests that the NLRP3 inflammasome plays a significant role in the pathophysiology of chronic pain, particularly in neuropathic and inflammatory pain conditions.
INFLAMMOPHARMACOLOGY
(2023)
Article
Pharmacology & Pharmacy
Weizhi Xu, Vinod Kumar, Cedric S. Cui, Xaria X. Li, Andrew K. Whittaker, Zhi Ping Xu, Maree T. Smith, Trent M. Woodruff, Felicity Y. Han
Summary: This study demonstrates the use of poly(lactic-co-glycolic) acid nanoparticles to enhance the oral bioavailability and therapeutic potential of cyclic hexapeptide complement C5a receptor 1 antagonists. The nanoparticles not only facilitate prolonged release of the encapsulated peptide, but also significantly increase its oral bioavailability and pharmacological activity in vivo.
ADVANCED THERAPEUTICS
(2022)
Article
Medicine, Research & Experimental
Arjun Muralidharan, Susana G. Sotocinal, Noosha Yousefpour, Nur Akkurt, Lucas Lima, Shannon Tansley, Marc Parisien, Chengyang Wang, Jean-Sebastien Austin, Boram Ham, Gabrielle M. G. S. Dutra, Philippe Rousseau, Sioui Maldonado-Bouchard, Teleri Clark, Sarah F. Rosen, Mariam R. Majeed, Olivia Silva, Rachel Nejade, Xinyu Li, Stephania Donayre Pimentel, Christopher S. Nielsen, G. Gregory Neely, Chantal Autexier, Luda Diatchenko, Alfredo Ribeiro-da-Silva, Jeffrey S. Mogil
Summary: Mice with experimental nerve damage display long-lasting neuropathic pain behavior. Senescence in the spinal cord for 4 months results in the maintenance of pain and a decreased lifespan. Nerve injury increases the number of p53-positive cells in the spinal cord neurons, astrocytes, and microglia, with a male-specific increase observed only in microglia. Repeated administration of a p53-specific substance reverses pain hypersensitivity.
JOURNAL OF CLINICAL INVESTIGATION
(2022)
Article
Behavioral Sciences
Amine Bahi
Summary: Gestational environmental enrichment (EE) has protective effects on social stress-induced anxiety-like behaviors and excessive ethanol consumption through increasing BDNF levels.
PHARMACOLOGY BIOCHEMISTRY AND BEHAVIOR
(2024)
Article
Behavioral Sciences
Sarabesh Natarajan, Grant Abass, Lucas Kim, Corinne Wells, Amir H. Rezvani, Edward D. Levin
Summary: Multiple neural systems, including dopamine D1 receptors and glutamate NMDA receptors, are involved in nicotine reinforcement. Acute blockade of D1 receptors decreases nicotine self-administration, while acute blockade of NMDA receptors increases it. Chronic blockade of NMDA receptors decreases nicotine self-administration. Memantine attenuates the decrease in nicotine self-administration caused by chronic D1 antagonist SCH-23390.
PHARMACOLOGY BIOCHEMISTRY AND BEHAVIOR
(2024)
Article
Behavioral Sciences
David R. Maguire
Summary: The study found that Lorcaserin alone reduces ventilation and enhances the ventilatory-depressant effects of opioids. This suggests that combining a 5-HT2C receptor agonist with opioids may increase the risk of ventilatory depression without reducing abuse.
PHARMACOLOGY BIOCHEMISTRY AND BEHAVIOR
(2024)
Article
Behavioral Sciences
Fen Liu, Qing Tian, Hui-Ling Tang, Xiang Cheng, Wei Zou, Ping Zhang
Summary: This study demonstrates the attenuating effect of H2S on PD-associated depression by improving hippocampal synaptic plasticity.
PHARMACOLOGY BIOCHEMISTRY AND BEHAVIOR
(2024)
Article
Behavioral Sciences
Mehrsa Rahimi-Danesh, Mohammad-Ali Samizadeh, Amir-Ehsan Sajadi, Tara Rezvankhah, Salar Vaseghi
Summary: This study investigated the effects of lithium on freezing behavior and pain perception in a fear-conditioning model in rats. The results showed that lithium had no effect on freezing behavior and pain subthreshold in all rats. Extinction training decreased freezing behavior, with more efficacy in females. Gender differences were also observed in the effects of extinction training.
PHARMACOLOGY BIOCHEMISTRY AND BEHAVIOR
(2024)