Department of Pharmacology of Pain
This paper clarifies attenuated efficacy of opioid drugs in the treatment of neuropathic pain by demonstrating the presence of MOP and KOP receptors and the absence of the opioid DOP receptor on microglial cells. This finding may explain why DOP receptor agonists are inefficient in the treatment of neuropathic pain, as opposed to the attenuated effects of drugs acting through the other two opioid receptors and indicates future directions for the search for novel analgesics.
Blockade of CC Chemokine Receptor Type 3 Diminishes Pain and Enhances Opioid Analgesic Potency in a Model of Neuropathic Pain.
Katarzyna Pawlik, Agata Ciechanowska, Katarzyna Ciapała, Ewelina Rojewska, Wioletta Makuch, Joanna Mika
Frontiers in immunology, 10.3389/fimmu.2021.781310
Anna Piotrowska, Katarzyna Ciapała, Katarzyna Pawlik, Klaudia Kwiatkowski, Ewelina Rojewska, Joanna Mika
International journal of molecular sciences, 11074 10.3390/ijms222011074
The Kynurenine Pathway as a Potential Target for Neuropathic Pain Therapy Design: From Basic Research to Clinical Perspectives.
Katarzyna Ciapała, Joanna Mika, Ewelina Rojewska
International journal of molecular sciences, 11055 10.3390/ijms222011055
Nitric oxide modulates tapentadol antinociceptive tolerance and physical dependence.
Renata Wolińska, Patrycja Kleczkowska, Anna de Cordé-Skurska, Piotr Poznański, Mariusz Sacharczuk, Joanna Mika, Magdalena Bujalska-Zadrożny
European journal of pharmacology, S0014-2999(21)00398-8 10.1016/j.ejphar.2021.174245
Long pentraxin PTX3 is upregulated systemically and centrally after experimental neurotrauma, but its depletion leaves unaltered sensorimotor deficits or histopathology.
Marco Oggioni, Domenico Mercurio, Denise Minuta, Stefano Fumagalli, Katarzyna Popiolek-Barczyk, Marina Sironi, Agata Ciechanowska, Stefania Ippati, Daiana De Blasio, Carlo Perego, Joanna Mika, Cecilia Garlanda, Maria-Grazia De Simoni
Scientific reports, 10.1038/s41598-021-89032-7
Topical Treatments and Their Molecular/Cellular Mechanisms in Patients with Peripheral Neuropathic Pain-Narrative Review.
Magdalena Kocot-Kępska, Renata Zajączkowska, Joanna Mika, David J Kopsky, Jerzy Wordliczek, Jan Dobrogowski, Anna Przeklasa-Muszyńska
Pharmaceutics, 450 10.3390/pharmaceutics13040450
Mirogabalin-A Novel Selective Ligand for the α2δ Calcium Channel Subunit.
Renata Zajączkowska, Joanna Mika, Wojciech Leppert, Magdalena Kocot-Kępska, Małgorzata Malec-Milewska, Jerzy Wordliczek
Pharmaceuticals (Basel, Switzerland), 112 10.3390/ph14020112
Peripheral Mechanisms of Neuropathic Pain-the Role of Neuronal and Non-Neuronal Interactions and Their Implications for Topical Treatment of Neuropathic Pain.
Magdalena Kocot-Kępska, Renata Zajączkowska, Joanna Mika, Jerzy Wordliczek, Jan Dobrogowski, Anna Przeklasa-Muszyńska
Pharmaceuticals (Basel, Switzerland), 77 10.3390/ph14020077
Initiators of Classical and Lectin Complement Pathways Are Differently Engaged after Traumatic Brain Injury-Time-Dependent Changes in the Cortex, Striatum, Thalamus and Hippocampus in a Mouse Model.
Agata Ciechanowska, Katarzyna Ciapała, Katarzyna Pawlik, Marco Oggioni, Domenico Mercurio, Maria-Grazia De Simoni, Joanna Mika
International journal of molecular sciences, E45 10.3390/ijms22010045
Bidirectional Action of Cenicriviroc, a CCR2/CCR5 Antagonist, Results in Alleviation of Pain-Related Behaviors and Potentiation of Opioid Analgesia in Rats With Peripheral Neuropathy.
Klaudia Kwiatkowski, Katarzyna Pawlik, Katarzyna Ciapała, Anna Piotrowska, Wioletta Makuch, Joanna Mika
Frontiers in immunology, 10.3389/fimmu.2020.615327
The CCL2/CCL7/CCL12/CCR2 pathway is substantially and persistently upregulated in mice after traumatic brain injury, and CCL2 modulates the complement system in microglia.
Katarzyna Popiolek-Barczyk, Agata Ciechanowska, Katarzyna Ciapała, Katarzyna Pawlik, Marco Oggioni, Domenico Mercurio, Maria-Grazia De Simoni, Joanna Mika
Molecular and cellular probes, S0890-8508(20)30560-0 10.1016/j.mcp.2020.101671
Novel bifunctional hybrid compounds designed to enhance the effects of opioids and antagonize the pronociceptive effects of non-opioid peptides as potent analgesics in a rat model of neuropathic pain.
Anna Piotrowska, Joanna Starnowska-Sokół, Wioletta Makuch, Joanna Mika, Ewa Witkowska, Dagmara Tymecka, Angelika Ignaczak, Beata Wilenska, Aleksandra Misicka, Barbara Przewłocka
Novel hybrid compounds, opioid agonist+melanocortin 4 receptor antagonist, as efficient analgesics in mouse chronic constriction injury model of neuropathic pain.
Joanna Starnowska-Sokół, Anna Piotrowska, Joanna Bogacka, Wioletta Makuch, Joanna Mika, Ewa Witkowska, Magda Godlewska, Jowita Osiejuk, Sandra Gątarz, Aleksandra Misicka, Barbara Przewłocka
Neuropharmacology, S0028-3908(20)30300-2 10.1016/j.neuropharm.2020.108232
Metamizole relieves pain by influencing cytokine levels in dorsal root ganglia in a rat model of neuropathic pain.
Renata Zajaczkowska, Klaudia Kwiatkowski, Katarzyna Pawlik, Anna Piotrowska, Ewelina Rojewska, Wioletta Makuch, Jerzy Wordliczek, Joanna Mika
Pharmacological reports : PR, 10.1007/s43440-020-00137-8
CCR4 Antagonist (C021) Administration Diminishes Hypersensitivity and Enhances the Analgesic Potency of Morphine and Buprenorphine in a Mouse Model of Neuropathic Pain.
Joanna Bogacka, Katarzyna Ciapała, Katarzyna Pawlik, Klaudia Kwiatkowski, Jan Dobrogowski, Anna Przeklasa-Muszynska, Joanna Mika
Frontiers in immunology, 10.3389/fimmu.2020.01241
PRELUDIUM 12 2016/23/N/NZ7/00356 Determination of the mechanisms and potential targets for neuropathic pain therapy by investigating pharmacological interactions occurring between substances that modulates glial cells activity and opioid analgesics., Anna Piotrowska-Murzyn, PhD
PURPOSE OF THE RESEARCH: Currently used methods of treating neuropathic pain are unsatisfactory. Establishing an effective therapy which could improve the quality of life of those who suffer from this kind of pain remains a huge challenge. Despite many years of research in this field, the mechanism of formation and maintenance of neuropathic pain is still not fully understood. Recent studies, including ours, indicate that glia are the cells which play a vital role in the development of neuropathy. The aim of the proposed project is a thorough examination the role of GPCRs such as chemokine/opioid receptors located on the surface of glial cells. Moreover, we would like to analyze the changes in the level of endogenous factors which initiate and regulate the development of neuropathy and which occur as a consequence of the sciatic nerve damage. Importantly, we are planning to use primary cultures of microglia and astrocytes, which will hopefully provide us with a better understanding of the role of these cells in the pathology of pain. A biochemical analysis will be conducted in vivo and in vitro. These tests will allow us to determine the changes in the level of receptors (CCR5, CXCR3, μ) and algesic mediators (e.g. CCL2-5,11,13,21, CXCL4,9-11, IL-1β, IL-6, IL-18) which contribute to the formation of neuropathic pain as well as endogenous analgesic mediators (IL-1RA, IL-18BP, IL-10). In addition, the project will involve the pharmacological pain modulation by the use of antagonists of chemokine receptors and inhibitors of intracellular pathways (p38MAPK, ERK1/2 among others) and the evaluation of their analgesic activity as well as the effect on the balance between pro- and anti-nociceptive factors. Minocycline, maraviroc and parthenolide are now used in the clinic, but not in the treatment of neuropathic pain. Their incorporation in our research can provide new evidence for their therapeutic effects. We are also planning to combine the administration of conventionally used analgesic opioids (for example tramadol) with selected immunomodulatory substances characterized by the highest analgesic potential. This can contribute to the establishing of foundations for a new and effective combination therapy of neuropathic pain. The results obtained in the research will bring a better understanding of the neuroimmunological bases of the formation of neuropathic pain. On the other hand, the results will enable us to evaluate the effectiveness of pharmacological substances used in relieving pain.RESEARCH HYPOTHESIS:1. In a rat/mouse model of neuropathic pain: 1.1 Chemokine receptor antagonists and inhibitors of intracellular pathways reduce pain by restoring the balance between pro- and anti-nociceptive factors. 1.2 Combined administration of opioid receptor agonist and chemokine receptor antagonist produces a synergistic analgesic effect. 1.3 Microglial cells and astrocytes are the source of the investigated nociceptive factors, therefore they are the target of pharmacological modulation. 2. In a primary culture of microglia and/or astrocytes: Pharmacological modulation of chemokine receptors and intracellular pathways important in nociception will enable us to understand their role and determine their impact on the effects of opioids. RESEARCH METHODOLOGY: Animals: All experiments will be conducted in accordance with the guidelines of the Animal Research Ethics Committee of the Institute of Pharmacology of the Polish Academy of Sciences in Krakow. Model of neuropathic pain (Bennett model): Unilateral loose ligation of the sciatic nerve in rats and/or mice. Administration of studied compounds: Intraperitoneal/subarachnoid administration of substances such as antagonists of chemokine receptors, inhibitors of intracellular pathways, agonist of opioid receptors: tramadol). Behavioral tests: Von Frey and cold plate tests. Biochemical tests: RNA Analysis: qRT-PCR. Protein analysis: Western blot/ELISA/Protein microarrays/Immunohistochemistry. Cell cultures: Primary cultures of microglia and/or astroglia. IMPACT OF THE RESULTS: According to the International Association for the Study of Pain IASP, one in five Europeans suffers from chronic pain. Symptoms which accompany the pain contribute to a significant deterioration of the quality of life. Therefore, development of an effective method of treatment is such an important issue. Defining the role of a number of immunological factors which are released during the development of neuropathy by glial cells will allow us to understand its pathomechanism and expand our knowledge in this field. Suggested research focuses on microglia and astrocytes, which have been recently recognized as important modulators of nociception. The results obtained in the project will complement the knowledge on the effects of analgesic drugs such as minocycline, parthenolide and maraviroc which are used in the clinic, but not in the treatment of neuropathy. Moreover, the use of new substances such as CXCR3 antagonist will contribute to the understanding of mechanisms conditioning the generation and maintenance of neuropathic pain. Combined administrations of analgesic opioids, which are currently used in the clinic, along with substances blocking the activity of glial cells via their receptors or intracellular pathways, can increase the efficiency of these opioids. This may result in enhancing the quality of life of patients suffering from neuropathic pain. Therefore, it seems that the pharmacological modulation of glia is a new and promising therapeutic approach in the treatment of a painful neuropathy.
Scientific award of L’Oréal Unesco For Women In Science, Anna Piotrowska-Murzyn, PhD
Wednesday, 14 November 2018
START Scholarship Foundation for Polish Science (FNP), Anna Piotrowska-Murzyn, PhD
Saturday, 26 May 2018
scholarship for outstanding scientific achievements awarded by President of the Polish Academy of Sciences, Anna Piotrowska-Murzyn, PhD
Wednesday, 13 December 2017
- ambiguous-cue interpretation
- behavioural analysis
- chronic pain
- G-protein coupled receptors
- gene expression
- hybrid compounds
- immune system
- microglia polarization
- molecular biology
- neuropathic pain
- opioid receptors
- signaling proteins