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Emerging importance of satellite glia in nervous system function and dysfunction

Nature Reviews Neuroscience volume 21, pages 485–498 (2020)Cite this article

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An Author Correction to this article was published on 22 October 2020

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Abstract

Satellite glial cells (SGCs) closely envelop cell bodies of neurons in sensory, sympathetic and parasympathetic ganglia. This unique organization is not found elsewhere in the nervous system. SGCs in sensory ganglia are activated by numerous types of nerve injury and inflammation. The activation includes upregulation of glial fibrillary acidic protein, stronger gap junction-mediated SGC–SGC and neuron–SGC coupling, increased sensitivity to ATP, downregulation of Kir4.1 potassium channels and increased cytokine synthesis and release. There is evidence that these changes in SGCs contribute to chronic pain by augmenting neuronal activity and that these changes are consistent in various rodent pain models and likely also in human pain. Therefore, understanding these changes and the resulting abnormal interactions of SGCs with sensory neurons could provide a mechanistic approach that might be exploited therapeutically in alleviation and prevention of pain. We describe how SGCs are altered in rodent models of four common types of pain: systemic inflammation (sickness behaviour), post-surgical pain, diabetic neuropathic pain and post-herpetic pain.

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Fig. 1: Location and morphology of SGCs.
Fig. 2: Mechanisms of signal spread in sensory ganglia and their possible contribution to chronic pain.
Fig. 3: Injury-induced changes in neuron–SGC bidirectional communications.
Fig. 4: Proposed sequence of events connecting nerve injury in four different pain models to SGC activation and neuronal hyperexcitability.

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  • 22 October 2020

    An amendment to this paper has been published and can be accessed via a link at the top of the paper.

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Acknowledgements

The authors were supported by the Israel Science Foundation (ISF 508/13 and ISF 1297/18 to M.H.), US–Israel Binational Science Foundation (BSF-2011044 to M.H. and D.C.S.) and NIH (R01NS092786, R01NS092466 and R21NS116892 to D.C.S.).

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  1. Laboratory of Experimental Surgery, Hadassah-Hebrew University Medical Center and Faculty of Medicine, Hebrew University of Jerusalem, Jerusalem, Israel

    Menachem Hanani

  2. Dominick Purpura Department of Neuroscience, Albert Einstein College of Medicine, New York, NY, USA

    David C. Spray

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Glossary

Satellite glial cells

(SGCs). Glial cells that surround neurons in sensory, sympathetic and parasympathetic ganglia (they should not be confused with satellite cells, which are the progenitor cells in striated muscles).

Sympathetic ganglia

Clusters of neuron cell bodies that innervate smooth muscles, heart and glands; paravertebral ganglia are arranged along the spinal column, and prevertebral ones are located in the abdomen.

Dorsal root ganglia

(DRG). Clusters of cells located near the spinal cord containing the cell bodies of peripheral neurons that innervate most body parts, including internal organs.

Sensory ganglia

Clusters of neuron cell bodies that have a single axon that bifurcates to two branches; one branch runs to the periphery and can detect various stimuli, and the other projects into the central nervous system.

P2 purinergic receptors

(P2Rs). Receptors for the neurotransmitter adenosine (P1) and ATP (P2). There are seven ionotropic receptors (P2X1–P2X7) and eight G protein-coupled receptors (P2Y1, P2Y2, P2Y4, P2Y6, P2Y11–P2Y14).

Trigeminal ganglia

(TG). Clusters of cells located at the base of the skull (but outside the brain) that contain the cell bodies of neurons that innervate the face, teeth and scalp.

Nodose ganglia

Clusters of neuron cell bodies that innervate many visceral organs, such as the intestine and heart.

Allodynia

Pain resulting from a non-noxious stimulus to normal skin.

Kir4.1 channels

Inward rectifier channels that tend to favour the influx of potassium ions into cells over their efflux.

Gap junctions

Intercellular channels that provide a pathway for diffusion of ions and small molecules between cells; they are made of connexin (Cx) proteins.

Dye coupling

A method for studying gap junction-mediated coupling between cells, based on injecting a cell with a dye that passes these junctions and examining whether the dye passed to nearby cells.

Neuralgia

Pain extending along the course of nerves; for example, trigeminal neuralgia.

Lipopolysaccharide

(LPS). A component of the wall of Gram-negative bacteria; LPS acts on Toll-like receptor 4 (TLR4), which, in sensory ganglia, is located on the surface of the sensory neurons.

Central sensitization

A state when the central nervous system becomes highly reactive, causing even mild stimuli to be sensed as painful.

Extracellular-signal regulated kinase

(ERK). A member of the MAP kinase family that is involved in multiple cellular processes.

DREADD

(Designer receptors exclusively activated by designer drugs). A method that utilizes G protein-coupled receptors engineered to respond exclusively to synthetic ligands.

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Hanani, M., Spray, D.C. Emerging importance of satellite glia in nervous system function and dysfunction. Nat Rev Neurosci 21, 485–498 (2020). https://doi.org/10.1038/s41583-020-0333-z

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