Glial cells and chronic pain
as a modulator of glial cells polarization - in vivo and in vitro
Piotrowska A, Kwiatkowski K, Rojewska E, Makuch W, Mika J.
Department of Pain Pharmacology, Institute of Pharmacology Polish Academy of Sciences, Krakow, Poland.
Studies conducted by the International Association for the Study of Pain indicate that every fifth European suffers from chronic pain. The implications of chronic pain include significant deterioration of life quality and even material status, since patients often have to face numerous symptoms which unable basic activities and make daily functioning so difficult. Many doctors and scientists have been seeking adequate treatment, which could contribute to the improvement of life conditions of patients suffering from neuropathic pain. Despite large volume of research, the mechanism of neuropathic pain development and maintenance remains unclear. Recent studies suggest that the efficacy of conventional analgesics may be increased by substances which modulate the activity of glial cells – crucial nervous system elements, often omitted in favor of neurons. It is believed that microglia, astrocytes and factors released by these cells are crucial for the initiation and development of neuropathic pain. Recently, it has been suggested that chemokines – small proteins from cytokine family – and their receptors are important for pain processing. Chemokine system consists of approximately 50 ligands and 20 receptors expressed by neurons and glial cells, and this promotes neuron-glia signaling. According to the latest research, CCR5 receptor and its ligands localized on glial cells surface play significant role in neuropathic pain development, and their modulation may have beneficial properties.
Fig. 1 The influence of maraviroc (MVC) on glial cells and nociceptive factors released in neuropathic pain
The main goal of our study was to examine the influence of CCR5 antagonist, maraviroc (MVC), on neuropathic pain symptoms and on the level of endogenous factors released after chronic constriction injury (CCI) of sciatic nerve (Bennett model), as well as on microglia and astrocytes in in vitro studies. We were able to demonstrate analgesic properties of maraviroc. Biochemical analysis showed that through the modulation of intracellular signaling pathways (phosphorylation of p38, ERK1/2, NF-κB, STAT3), maraviroc decreases CCI-elevated level of pronociceptive “classical” glial cells activation markers (IL-1β, IL-18, IL-6, NOS2), and increases antinociceptive “alternative” glial cells activation markers (IL-1RA, IL18BP, IL-10) (Fig.1). Similar effects were observed in our in vitro studies on primary glial cells cultures. Our current results determined the neuroimmunological foundation of neuropathic pain development and evaluation of analgesic properties of examined pharmacological tools. In conclusion, our results suggest that pharmacological modulation of CCR5 by maraviroc through the regulation of intracellular pathways and restoration of the balance between pro- and antinociceptive factors, may become a new therapeutic approach in neuropathic pain treatment.
Joanna Mika Phd
Department of Pharmacology of Pain
Piotrowska A, Kwiatkowski K, Rojewska E, Makuch W, Mika J. Maraviroc reduces neuropathic pain through polarization of microglia and astroglia - Evidence from in vivo and in vitro studies.
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