Role of microglia in neuropathic pain

Abstract

Microglial cells are specialized macrophage cells of the central nervous system responsible for the innate immunity of the spinal cord and the brain. They protect the brain and spinal cord from invaders, microbes, demyelination, trauma and remove defective cells and neurons. For immune protection, microglial cells possess a significant number of receptors and chemical mediators that allow them to communicate rapidly and specifically with all cells of the nervous tissue. 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. The present study is a narrative review focusing on the literature concerning the complex interaction between neurons and microglia in the development of neuropathic pain. Injury in the peripheral or central nervous system may result in maladaptive changes in neurons and microglial cells. In neuropathic pain, microglial cells have an important role in initiating and maintenance of pain and inflammation. The interaction between neural and microglial cells has been proven extremely crucial for chronic pain. The study of individual mechanisms at the level of the spinal cord and the brain is an interesting and groundbreaking research challenge. Elucidation of the mechanisms by which neurons and immune cells interact, could constitute microglial cells a new therapeutic target for the treatment of neuropathic pain.

Reactive spinal glia convert 2-AG to prostaglandins to drive aberrant astroglial calcium signaling

“…Participation of spinal astrocytes and microglia in the modulation of pain processing, however, can profoundly be influenced by their expression profiles. Reactive glia can release a set of inflammatory mediators including TNFα and IL-1β which can directly drive the development of central sensitization and a consequent persistent pain ( Tang et al, 2021 ; Karavis et al, 2023 ). Our data confirmed that neuroinflammatory astrocytes and microglia in the SDH in vivo and in vitro increase the expression of COX-2 resulting in an increased capacity for the oxygenation of arachidonic acid derivatives including 2-AG.…”

Editorial: Exploring neuroinflammatory pathways that contribute to chronic pain, volume II

“…Neuroinflammation can arise from a variety of sources most notably via transcription/translation of inflammatory mediators from the nucleus of the cell which ultimately lead to activated microgliosis. Microgliosis is a central hallmark of neuropathic pain where the amoeboid activated proinflammatory M1 phenotypic state has been implicated in the development and progression of neuropathic pain ( Karavis et al, 2023 ). Peroxisome proliferator-activated receptor gamma (PPAR γ), a member of a large group of nuclear receptors controlling the proliferation of peroxisomes has been shown to have anti-inflammatory functions in several macrophagous cell types (references in Li et al via inhibition of microglia activation and ultimately reduction in neuroinflammation).…”