Abstract
Chronic pain is known to be caused by sensitization within the pain circuits. An imbalance occurs between excitatory and inhibitory transmission that enables this sensitization to form. In addition to neurons, the contribution of central glia, especially astrocytes and microglia, to the pathogenesis of pain induction and maintenance has been identified. This has led to the targeting of astrogliosis and microgliosis to restore the normal functions of astrocytes and microglia to help reverse chronic pain. Gliosis is broadly defined as a reactive response of glial cells in response to insults to the central nervous system (CNS). The role of glia in the peripheral nervous system (PNS) has been less investigated. Accumulating evidence, however, points to the contribution of satellite glial cells (SGCs) to chronic pain. Hence, understanding the potential role of these cells and their interaction with sensory neurons has become important for identifying the mechanisms underlying pain signaling. This would, in turn, provide future therapeutic options to target pain. Here, a viewpoint will be presented regarding potential future directions in pain research, with a focus on SGCs to trigger further research. Promising avenues and new directions include the potential use of cell lines, cell live imaging, computational analysis, 3D tissue prints and new markers, investigation of glia–glia and macrophage–glia interactions, the time course of glial activation under acute and chronic pathological pain compared with spontaneous pain, pharmacological and non-pharmacological responses of glia, and potential restoration of normal function of glia considering sex-related differences.
Highlights
Chronic pain is a debilitating and common condition [1], and it has a substantial impact on affected individuals, society, and the health-care system [2]
An argument has been formed around preference in targeting these cells, as satellite glial cells (SGCs) are located outside the blood–brain barrier (BBB), which might offer a better potential for blocking pain transmission at the periphery
SGCs were considered cells that share some common features with astrocytes; the expression of some proteins that were known for astrocytes was expected in these cells, such as glial fibrillary acidic protein (GFAP), glutamine synthetase, glutamate aspartate transporter, and connexin 43 gap junction [31, 38]
Summary
Chronic pain is a debilitating and common condition [1], and it has a substantial impact on affected individuals, society, and the health-care system [2]. SGC alterations have been documented in response to both injury and inflammation These cells, have become another potential target for therapeutic purposes, i.e., for the prevention or treatment of chronic pain. An argument has been formed around preference in targeting these cells, as SGCs are located outside the blood–brain barrier (BBB), which might offer a better potential for blocking pain transmission at the periphery Considering that these cells seem first to respond to injury or inflammation prior to central glial cells, they may offer potential for minimizing the risk of chronification and transition from peripheral to central sensitization [15, 33]. Further investigation of glia in relation to pain and its targeting is a truly fascinating field of science and highly valuable in understanding pain mechanisms and mechanistic-based optimized targeting
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