The Similar and Distinct Roles of Satellite Glial Cells and Spinal Astrocytes in Neuropathic Pain

Cells, 2023 · DOI: https://doi.org/10.3390/cells12060965 · Published: March 22, 2023

Simple Explanation

Preclinical studies suggest glial cells play a key role in neuropathic pain following nerve injury from conditions like diabetes and chemotherapy. Satellite glial cells (SGCs) in the peripheral nervous system and astrocytes in the central nervous system share molecular markers and protective functions under normal conditions. In neuropathic pain, SGCs and astrocytes behave similarly by reducing homeostatic functions and promoting inflammation in the nervous system. However, SGCs are not simply 'peripheral astrocytes'. These glial cells contribute differently to neuropathic pain by producing distinct mediators, interacting with different parts of neurons, and activating at different times after nerve injury. Recent findings show SGCs are rich in proteins related to fatty acid metabolism.

Study Duration

Not specified

Participants

Not specified

Evidence Level

Review

Key Findings

1
Satellite glial cells (SGCs) and astrocytes, while sharing critical functions, are not entirely congruent in their responses to nerve injury and activate on different timescales. SGCs become active rapidly (hours to days), while astrocytes in the dorsal horn show changes after days to weeks.
2
SGCs and astrocytes both upregulate GFAP after nerve injury, contributing to reactive gliosis. However, there are inconsistencies in RNAseq data regarding GFAP expression in SGCs, suggesting regulation at translational or protein degradation levels.
3
Recent data suggests SGCs are enriched with proteins related to fatty acid metabolism and signaling such as Apo-E, FABP7, and LPAR1.

Research Summary

Astrocytes and satellite glia play important and similar roles in the induction and maintenance of neuropathic pain. In conditions of neuropathic pain, both cell types upregulate GFAP, although astrocytes have more been convincingly demonstrated to undergo hypertrophy and proliferation. Both glia consistently engage in bidirectional pro-inﬂammatory signaling through cytokines such as IL-6, TNFα, and IL-1β, and astrocytes also release CCL2/CXCL1 and TSP4. SGCs more reliably downregulate the potassium channel Kir4.1 and increase their expression of the ATP-gated cation channel P2X7.

Practical Implications

Targeting SGCs

The location of SGCs in the PNS allows them to be readily targeted with CNS-impermeable drugs, avoiding the side effects of many CNS drugs.

Targeting Astrocytes

The critical role of astrocytes in the late phase of neuropathic pain suggests that successfully targeting them in the CNS may offer greater leverage.

Novel therapeutics

Targeting SGCs and astrocytes may lead to novel therapeutics for the treatment of neuropathic pain.

Study Limitations

1
Morphological changes in SGCs following nerve injury are a matter of current controversy.
2
The extent to which SGCs engage in functions such as phagocytosis and antigen presentation remains unknown
3
The role of SGC-expressed P2X7 in neuropathic pain is unclear.

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