Supervisors info:
Γεώργιος Γεωργούδης, Αναπληρωτής Καθηγητής, Τμήμα Φυσικοθεραπείας, Πανεπιστήμιο Δυτικής Αττικής
Ιωάννα Σιάφακα, Καθηγήτρια, Ιατρική Σχολή, ΕΚΠΑ
Αθηνά Βαδαλούκα, Αναπληρώτρια Καθηγήτρια, Ιατρική Σχολή, ΕΚΠΑ
Summary:
Background: Microglia cells are highly dynamic immune cells of CNS, accounting for 5-20% of the total glial cell population and 10% of all cells found in the CNS. Microglial cells, serve as the brain’s resident macrophage, modulate neural activity and are responsible for the innate immunity of the spinal cord and the brain. These multifunctional cells detect, protect and repair synapses, neural circuits, pathways and networks. They are surveyors of the brain’s health, continuously monitor their surroundings and patrol brain and spinal regions. Besides, they control and evaluate the functionality of the synapses, giving priority to the healthy ones that are used more frequently and those protecting more effectively the neural networks. For the fulfillment of these complicated tasks, the microglial cells has in its arsenal an impressive number of receptors and chemical modulators and mediators, which are used to communicate with neurons and the adjacent macroglial cells of the neural tissue. They promptly respond to micro environmental variations and pathological changes. They can selectively modify their polarization (M1, M2 and dark) by altering morphology, phenotype and function. In the last years the emerging roles of microglia are investigated in animals and humans, as well as in healthy and diseased subjects. The research has shown that microglia can impact overall brain function as immune modulator cells, having also an important role in initiating and/or maintaining neuropathic pain, central sensitization and synaptic plasticity (long term potentiation). The contribution of microglia in neuropathic pain challenges conventional concepts toward neurons being the only structure responsible for the pathophysiological changes that drive neuropathic pain. This shift in our understanding, provide us with new research tools, new perspective and hope of new disease modifying therapeutic strategies.
Purpose: The present thesis focuses on and critically review of the bibliography concerning the complex interaction between neurons and microglia during development, neuropathic pain and neuroinflammation. We have studied the results and the key findings of the recent studies published from 2006 till 2018. We have reviewed animal studies, clinical research articles and surveys examining spinal and brain mechanisms of microglia activation and inhibition during a variety of neuropathic pain states, neuroinflammatory and neurodegenerative diseases.
Methods: This is a hybrid narrative review, which consists of almost all essential steps of a systemic research, except the statistical data analysis. We have searched the database on Medline via PubMed using the words neuropathic pain, microglia, neuroplasticity, mechanisms, with no date restriction. Additional articles and prime references were obtained by free internet search, but we used only those articles that were already published. We considered animal studies, experimental and clinical trials and review articles published in English. We organized our articles by inputting the information extracted in a book code (excel file) with four main categories of entry: general features that mark the quality of the studies, articles that …the way in which cellular and molecular mechanisms alter baseline microglial behavior, according to anatomical region of microglia activation and finally the therapeutic strategies targeting at microglial priming during neuropathic pain, neuroinflammation and neurodegeneration.
Results / conclusion: Microglial cells are responsible for immune surveillance within the central nervous system. Injury in the peripheral or central nervous system may result in maladaptive changes in neurons and microglial cells along the nociceptive pathway (microgliosis). During the aforementioned changes, in neuropathic pain, microglial cells have an important role in initiating and maintenance of pain and inflammation. More specific, disruption of microglial homeostasis may lead to chronic neuropathic pain, neuroinflammation and neurodegeneration. The groundbreaking mechanisms by which neurons and immune cells interact have been the subject of increasing state of the art research over the last two decades. The former researching trend demonstrated that the immune system in collaboration with somatosensory system are specialized and functionally oriented toward the capacity to protect the body and identify the noxious environmental and micro environmental stimuli. Microglia, through communication, synergy and mutual interaction with the nerve cells contribute to the immune response and immune homeostasis and consequently plays a significant role in the pathogenesis of some neuroimmune disorders. The interaction between neural and microglial cells has been proven extremely crucial for chronic pain, inflammation and neuroinflammation. These results could highlight the beginning for the development of new therapeutic strategies for treating neurodegenerative diseases and neuropathic pain conditions. We are convinced that the technical issues will be solved and in the near future microglia will be the new target in treating neuropathic pain syndromes. Moreover, we are positive that in the near future we will be able to control the excessive activation of the microglial cells without disrupting his homeostatic and immuneprotective role.
Keywords:
Microglia, Microglial cells, Neuropathic, Pain, Neuroinflammation, Neuroplasticity, Antinociception, Central sensitization, Rehabilitation
