Article
Pharmacology & Pharmacy
Lawrence M. Carey, Zhili Xu, Gabriela Rajic, Alexandros Makriyannis, Julian Romero, Cecilia Hillard, Ken Mackie, Andrea G. Hohmann
Summary: This study suggests that CB2 activation may alleviate HIV-associated antiretroviral neuropathy and identifies a previously unreported mechanism through which CB2 activation produces antinociceptive efficacy. The study also demonstrates that a CB2 agonist can reverse established morphine tolerance and shows that CB2 localized to peripheral sensory neurons mediates the opioid tolerance sparing efficacy of CB2 agonists.
PHARMACOLOGICAL RESEARCH
(2023)
Article
Multidisciplinary Sciences
Sara Caxaria, Sabah Bharde, Alice M. Fuller, Romy Evans, Bethan Thomas, Petek Celik, Francesco Dell'Accio, Simon Yona, Derek Gilroy, Mathieu-Benoit Voisin, John N. Wood, Shafaq Sikandar
Summary: We demonstrated the role of neutrophils in fibromyalgia by using a back-translational approach in mice. Adoptive transfer of neutrophils from mice with chronic widespread pain or patients with fibromyalgia can induce mechanical pain in recipient mice, sensitize spinal cord neurons, and cause changes in the expression of neutrophil proteins that lead to neutrophil infiltration into dorsal root ganglia. These findings suggest an immunological basis for chronic widespread pain in fibromyalgia mediated by neutrophils.
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA
(2023)
Article
Neurosciences
Hourong Wang, Zhifeng Liu, Tianyuan Yu, Yingqi Zhang, Yajing Xu, Yi Jiao, Qian Guan, Di Liu
Summary: This study analyzed the changes in gene expression in the dorsal root ganglia (DRG) and spinal dorsal horn (SDH) after tuina treatment and investigated the immediate analgesic mechanism of tuina. The results showed that tuina improved nociceptive behavior in rats with minor chronic constriction injury (CCI), especially in thermal hyperalgesia. Additionally, analysis of differentially expressed genes (DEGs) revealed that the immediate analgesic mechanism of tuina is associated with the calcium signaling pathway, thermogenesis, and regulation of lipolysis in adipocytes.
FRONTIERS IN NEUROSCIENCE
(2022)
Article
Neurosciences
Kelsey G. Guenther, Zhili Xu, Julian Romero, Cecilia J. Hillard, Ken Mackie, Andrea G. Hohmann
Summary: CB2 agonists can suppress pathological pain in animal models without unwanted side effects associated with CB1 receptor activation. However, the specific types of pain responsive to CB2 agonists and the cell types underlying therapeutic efficacy are not fully understood.
Review
Chemistry, Medicinal
Jaeik Park, Jueun Roh, Jingying Pan, Yong Ho Kim, Chul-Kyu Park, Youn Yi Jo
Summary: Chronic pain is an unpleasant experience associated with tissue damage, and it can be caused by inflammation or somatosensory damage. Inflammation plays a significant role in the progression of both types of pain, and resolvins derived from omega-3 fatty acids have shown promise in alleviating inflammatory and neuropathic pain by reducing hypersensitivity and regulating inflammatory cytokines and glial activation.
Article
Chemistry, Medicinal
Rahul Nachnani, Diana E. Sepulveda, Jennifer L. Booth, Shouhao Zhou, Nicholas M. Graziane, Wesley M. Raup-Konsavage, Kent E. Vrana
Summary: Cannabigerol (CBG), derived from the cannabis plant, acts as an acute analgesic in a model of cisplatin-induced peripheral neuropathy (CIPN) in mice. Chronic CBG administration was found to alleviate mechanical hypersensitivity due to CIPN without tolerance or adverse events.
Article
Biochemistry & Molecular Biology
Ruirui Lu, Katharina Metzner, Fangyuan Zhou, Cathrin Flauaus, Annika Balzulat, Patrick Engel, Jonas Petersen, Rebekka Ehinger, Anne Bausch, Peter Ruth, Robert Lukowski, Achim Schmidtko
Summary: The sodium-activated potassium channel Slack plays a role in sensory neurons and is involved in mediating sodium-activated potassium current (I-KNa) and modulating neuronal activity. Studies found that Slack activity is reduced in sensory neurons after peripheral nerve injury, contributing to neuropathic pain hypersensitivity, and that it is associated with ATP-sensitive P2X3 receptors. Experiments showed that Slack-mediated I-KNa can be bidirectionally modulated in response to P2X3 activation, suggesting a potential novel strategy for treating neuropathic pain.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2021)
Article
Cell Biology
Fangyuan Zhou, Katharina Metzner, Patrick Engel, Annika Balzulat, Marco Sisignano, Peter Ruth, Robert Lukowski, Achim Schmidtko, Ruirui Lu
Summary: The study reveals that Slack serves as a modulator of TRPA1-mediated activation of sensory neurons, but not TRPV1-mediated activation.
Article
Clinical Neurology
Ricardo H. Roda, David Bargiela, Weiran Chen, Ken Perry, Ronald J. Ellis, David B. Clifford, Ajay Bharti, Asha R. Kallianpur, Michelli F. Oliveira, Monica M. Diaz, Leah H. Rubin, Christina Gavegnano, Justin C. McArthur, Ahmet Hoke, Michael Polydefkis
Summary: The study aimed to evaluate the correlation of large mtDNA deletions in skin samples of people with HIV with measures of neuropathy and prior exposure to therapy. Results showed a correlation between the total mtDNA deletion and intraepidermal nerve fiber density (IENFD) and sural nerve amplitude in PWH with HIV-associated sensory neuropathy.
Article
Biology
Minh Q. Nguyen, Lars J. von Buchholtz, Ashlie N. Reker, Nicholas J. P. Ryba, Steve Davidson
Summary: Through single nuclear transcriptomics of human DRG neurons, it was found that different types of neurons share similarities in their transcriptomic features, but there are species differences in the expression of genes related to sensory function. Surprisingly, several transcriptomic classes without clear equivalents in other species were identified.
Article
Biochemistry & Molecular Biology
Tomislav Kokotovic, Ewelina M. Lenartowicz, Michiel Langeslag, Cosmin Ciotu, Christopher W. Fell, Angelica Scaramuzza, Michael J. M. Fischer, Michaela Kress, Josef M. Penninger, Vanja Nagy
Summary: MEOX2 is an important transcription factor involved in the differentiation of mesoderm and plays a role in the development of various tissues. This study demonstrates the significance of MEOX2 in the mammalian peripheral nervous system, particularly in nociception. MEOX2 regulates the expression of Na(v)1.7 and Na(v)1.9 voltage-gated sodium channels, which are essential for action potential initiation in nociceptors. Additionally, MEOX2 is involved in maintaining the transcriptional program associated with pain perception.
Article
Neurosciences
Laszlo Ducza, Andrea Gajtko, Krisztina Hegedus, Erzsebet Bakk, Greta Kis, Botond Gaal, Roland Takacs, Peter Szucs, Klara Matesz, Krisztina Hollo
Summary: This study provides new evidence for the involvement of neuronal and glial P2X4 receptors in the development of inflammatory pain.
FRONTIERS IN MOLECULAR NEUROSCIENCE
(2023)
Article
Clinical Neurology
Pradipta R. Ray, Stephanie Shiers, James P. Caruso, Diana Tavares-Ferreira, Ishwarya Sankaranarayanan, Megan L. Uhelski, Yan Li, Robert Y. North, Claudio Tatsui, Gregory Dussor, Michael D. Burton, Patrick M. Dougherty, Theodore J. Price
Summary: This study characterized the molecular changes in pain-associated human dorsal root ganglia in patients undergoing thoracic vertebrectomy, revealing sex differences in underlying mechanisms of neuropathic pain. The findings provide important insights for pain treatment.
Article
Chemistry, Multidisciplinary
Jia-wen Xu, Xu Xu, Yun Ling, Yan-chun Wang, Yu-jie Huang, Juan-zhen Yang, Jia-ying Wang, Xu Shen
Summary: Diabetic peripheral neuropathy (DPN) is a common complication of diabetes without cure. In this study, the therapeutic potential of vincamine (Vin), a GPR40 agonist, in ameliorating DPN-like pathology was evaluated in diabetic mice. The results showed that Vin administration improved neurological dysfunctions, blood flow velocities, blood perfusion areas, myelin sheath injury, and intraepidermal nerve fiber density impairment in DPN mice, suggesting that pharmacological activation of GPR40 could be a promising therapeutic strategy for DPN.
ACTA PHARMACOLOGICA SINICA
(2023)
Article
Pharmacology & Pharmacy
Lin Yao, Tian-Yu Zhang, Xin-Tong Diao, Juan-Juan Ma, Hu-Hu Bai, Zhan-Wei Suo, Yan-Ni Liu, Xian Yang, Xiao-Dong Hu
Summary: The glycine receptor, consisting of α1 subunits, plays a crucial role in inhibitory neurotransmission and may serve as an effective target for pain therapy in the peripheral nervous system. Inflammation in the periphery can reduce the expression of glycine receptors on the plasma membrane of neurons. Glycine receptor agonists or positive modulators show promise in alleviating pain behaviors induced by inflammation.
EUROPEAN JOURNAL OF PHARMACOLOGY
(2021)
Review
Biochemistry & Molecular Biology
Silvia Pasquini, Chiara Contri, Stefania Merighi, Stefania Gessi, Pier Andrea Borea, Katia Varani, Fabrizio Vincenzi
Summary: Adenosine plays an important role in regulating CNS activity, and its receptors are promising therapeutic targets for neuropsychiatric disorders.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2022)
Review
Biochemistry & Molecular Biology
Stefania Merighi, Manuela Nigro, Alessia Travagli, Silvia Pasquini, Pier Andrea Borea, Katia Varani, Fabrizio Vincenzi, Stefania Gessi
Summary: The A(2A) adenosine receptor plays a crucial role in neurodegenerative diseases such as Alzheimer's disease (AD) by regulating synaptic transmission and neuroinflammation. The NLRP3 inflammasome also plays an important role in AD pathogenesis, and adenosine through the A(2A) receptor modulates NLRP3 function for neuroprotection.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2022)
Review
Biochemistry & Molecular Biology
Ula von Mentzer, Carmen Corciulo, Alexandra Stubelius
Summary: Articular joint defects are becoming more prevalent due to rising obesity rates and an aging population. Joint replacement is often the last resort for patients with cartilage erosion, and researchers are exploring novel strategies to promote regeneration and healing. The use of decellularized extracellular matrix (dECM) biomaterials shows promise in reducing foreign body responses and enhancing tissue regeneration.
MACROMOLECULAR BIOSCIENCE
(2022)
Review
Biochemistry & Molecular Biology
Stefania Merighi, Pier Andrea Borea, Katia Varani, Fabrizio Vincenzi, Alessia Travagli, Manuela Nigro, Silvia Pasquini, R. Rama Suresh, Sung Won Kim, Nora D. Volkow, Kenneth A. Jacobson, Stefania Gessi
Summary: The A(2A) adenosine receptor plays an important role in Alzheimer's disease and can be counteracted by antagonists to relieve clinical symptoms. Research has also found that the pharmacokinetics and ability to pass the blood-brain barrier are crucial in the discovery of new drugs for CNS disorders.
Article
Immunology
Emma Boberg, Julie Weidner, Carina Malmhall, Jenny Calven, Carmen Corciulo, Madeleine Radinger
Summary: The mTORC1 signaling pathway plays an important role in IL-33-induced bone marrow ILC2 responses, and rapamycin treatment successfully decreases IL-33-induced eosinophilic inflammation, possibly by inhibiting IL-5-producing bone marrow ILC2 cells.
FRONTIERS IN IMMUNOLOGY
(2022)
Article
Biochemistry & Molecular Biology
Micaela Tirri, Raffaella Arfe, Sabrine Bilel, Giorgia Corli, Beatrice Marchetti, Anna Fantinati, Fabrizio Vincenzi, Fabio De-Giorgio, Cristian Camuto, Monica Mazzarino, Mario Barbieri, Rosa Maria Gaudio, Katia Varani, Pier Andrea Borea, Francesco Botre, Matteo Marti
Summary: This study compared the pharmacodynamic activity of synthetic cannabinoids JWH-175 and JWH-018 in vitro and in vivo, and evaluated the metabolic profile of JWH-175. The results showed that JWH-175 is a less potent cannabinoid receptor agonist compared to JWH-018 and is rapidly converted to JWH-018 in vivo. This study provides important insights into the pharmacotoxicological profile of JWH-175 and emphasizes the importance of studying the in vivo metabolism of synthetic cannabinoids for clinical toxicology and forensic purposes.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2022)
Review
Biochemistry & Molecular Biology
Paola Tedeschi, Manuela Nigro, Alessia Travagli, Martina Catani, Alberto Cavazzini, Stefania Merighi, Stefania Gessi
Summary: Garlic contains bioactive compounds with anti-inflammatory, antioxidant, and neuroprotective properties. Research has shown that garlic and its components may have potential therapeutic effects on dementia, including Alzheimer's disease. This paper reviews the chemical composition, metabolism, and bioavailability of garlic bioactive compounds, as well as the signaling mechanisms triggered by garlic derivatives for improving learning and memory.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
(2022)
Article
Endocrinology & Metabolism
Carmen Corciulo, Julia M. Scheffler, Piotr Humeniuk, Alicia Del Carpio Pons, Alexandra Stubelius, Ula Von Mentzer, Christina Drevinge, Aidan Barrett, Sofia Wuestenhagen, Matti Poutanen, Claes Ohlsson, Marie K. Lagerquist, Ulrika Islander
Summary: This study investigated the effect of deficiency of female sex steroids on the progression of knee osteoarthritis (OA) and evaluated the protective role of treatment with a physiological dose of 17 beta-estradiol (E2). The findings demonstrate that E2 treatment can alleviate OA symptoms and protect against bone loss in postmenopausal women with OA.
JOURNAL OF ENDOCRINOLOGY
(2022)
Article
Chemistry, Medicinal
Teresa Gianferrara, Matteo Pavan, Davide Bassani, Fabrizio Vincenzi, Silvia Pasquini, Giovanni Bolcato, Katia Varani, Giampiero Spalluto, Stephanie Federico, Stefano Moro
Summary: Traditionally, molecular recognition between adenosine receptors and their ligands has been thought to occur with a 1:1 stoichiometry. However, recent simulations suggest an alternative 2:1 binding stoichiometry. In this study, a bis-ribosyl adenosine derivative, BRA1, was synthesized and tested for its binding and activation abilities on adenosine receptors, with molecular modeling used to rationalize its activity.
Review
Biochemistry & Molecular Biology
Stefania Merighi, Alessia Travagli, Manuela Nigro, Silvia Pasquini, Martina Cappello, Chiara Contri, Katia Varani, Fabrizio Vincenzi, Pier Andrea Borea, Stefania Gessi
Summary: Alzheimer's disease (AD) is the most common form of dementia, with an estimated 135 million cases worldwide by 2050. Current medications for AD only alleviate symptoms and do not modify the disease progression. Clinical studies suggest that caffeine, through its antagonistic action on A(2A) receptors, may have neuroprotective effects against neurodegenerative conditions like AD. This review highlights the critical role of A(2A) receptors in memory loss and cognitive decline, and the potential benefits of caffeine's antagonistic action on these receptors in neurodegeneration.
Article
Biochemistry & Molecular Biology
Paola Tedeschi, Federica Brugnoli, Stefania Merighi, Silvia Grassilli, Manuela Nigro, Martina Catani, Stefania Gessi, Valeria Bertagnolo, Alessia Travagli, Maria Fiorenza Caboni, Alberto Cavazzini
Summary: This study aims to examine the effect of storage on the phytochemical composition, biological effects, and shelf-life of Voghiera garlic PDO. The results showed that there were a decrease in sulfur compounds after 6 months which correlated to a decrease in bioactive effects, while the number of antioxidant compounds was stable during the storage period, indicating the good effect of refrigerated temperature in maintaining garlic bulb shelf-life.
Review
Pharmacology & Pharmacy
Mercedes Fernandez, Manuela Nigro, Alessia Travagli, Silvia Pasquini, Fabrizio Vincenzi, Katia Varani, Pier Andrea Borea, Stefania Merighi, Stefania Gessi
Summary: The blood-brain barrier (BBB) is a biological barrier that protects the central nervous system (CNS) and regulates the permeability of drugs. Activation of adenosine receptors (ARs) may modulate BBB permeability, which has potential implications for treating CNS disorders.
Article
Endocrinology & Metabolism
Julia M. Scheffler, Karin L. Gustafsson, Aidan Barrett, Carmen Corciulo, Christina Drevinge, Alicia M. Del Carpio Pons, Piotr Humeniuk, Cecilia Engdahl, Jan-Ake Gustafsson, Claes Ohlsson, Hans Carlsten, Marie K. Lagerquist, Ulrika Islander
Summary: This study reveals the importance of ER alpha signaling in CAR cells for bone health and provides insights into the effects of hormones on the immune system and bone density.