title: The purinergic system and glial cells: emerging costars in nociception.
abstract: It is now well established that glial cells not only provide mechanical and trophic support to neurons but can directly contribute to neurotransmission, for example, by release and uptake of neurotransmitters and by secreting pro- and anti-inflammatory mediators. This has greatly changed our attitude towards acute and chronic disorders, paving the way for new therapeutic approaches targeting activated glial cells to indirectly modulate and/or restore neuronal functions. A deeper understanding of the molecular mechanisms and signaling pathways involved in neuron-to-glia and glia-to-glia communication that can be pharmacologically targeted is therefore a mandatory step toward the success of this new healing strategy. This holds true also in the field of pain transmission, where the key involvement of astrocytes and microglia in the central nervous system and satellite glial cells in peripheral ganglia has been clearly demonstrated, and literally hundreds of signaling molecules have been identified. Here, we shall focus on one emerging signaling system involved in the cross talk between neurons and glial cells, the purinergic system, consisting of extracellular nucleotides and nucleosides and their membrane receptors. Specifically, we shall summarize existing evidence of novel "druggable" glial purinergic targets, which could help in the development of innovative analgesic approaches to chronic pain states.
authors.affiliation: Department of Pharmacological and Biomolecular Sciences, Università degli Studi di Milano, Via Balzaretti, 9-20133 Milan, Italy ; Department of Drug Discovery and Development (D3), Italian Institute of Technology (IIT), Via Morego, 30-16163 Genoa, Italy.
authors.forename: Giulia
authors.identifier: 0000-0003-0995-8947
authors.initials: G
authors.lastname: Magni
authors.affiliation: Department of Pharmacological and Biomolecular Sciences, Università degli Studi di Milano, Via Balzaretti, 9-20133 Milan, Italy.
authors.forename: Stefania
authors.identifier: 0000-0003-1663-4211
authors.initials: S
authors.lastname: Ceruti
mesh_terms: D000700:Analgesics / Q000494:pharmacology / Q000627:therapeutic use; D000818:Animals; D059350:Chronic Pain / Q000188:drug therapy / Q000503:physiopathology; D006801:Humans; D009457:Neuroglia / Q000187:drug effects / Q000378:metabolism*; D009474:Neurons / Q000187:drug effects / Q000378:metabolism; D059225:Nociception / Q000187:drug effects; D011983:Receptors, Purinergic / Q000378:metabolism*
chemical_list: D000700:Analgesics; D011983:Receptors, Purinergic