Inducible co‑stimulatory molecule (ICOS) alleviates paclitaxel‑induced neuropathic pain via an IL‑10‑mediated mechanism in female mice

Journal of Neuroinflammation, 2023 · DOI: https://doi.org/10.1186/s12974-023-02719-8 · Published: February 3, 2023

Simple Explanation

Chemotherapy-induced peripheral neuropathy (CIPN) is a side effect of chemotherapy that causes pain, and there are currently no effective treatments. This study investigates the role of the immune system in resolving CIPN pain using an immune checkpoint molecule called ICOS. The researchers found that activating ICOS with an agonist antibody (ICOSaa) alleviated mechanical hypersensitivity (increased sensitivity to touch) in female mice treated with paclitaxel, a chemotherapy drug. The pain relief was facilitated by an increase in the anti-inflammatory cytokine IL-10 in the dorsal root ganglion (DRG), a cluster of nerve cells in the spine. Blocking IL-10 reversed the pain-relieving effects of ICOSaa.

Study Duration

Not specified

Participants

8- to 12-week-old female and male littermates

Evidence Level

Not specified

Key Findings

1
ICOS agonist antibody (ICOSaa) promotes paclitaxel-evoked pain resolution in female mice.
2
ICOSaa treatment increases DRG levels of IL-10 cytokine.
3
ICOSaa effects in female mice are blocked by IL-10 sequestering treatment.

Research Summary

This study investigates the potential of inducible co-stimulatory molecule (ICOS) in resolving CIPN pain-like behaviors in mice, finding that ICOS agonist antibody (ICOSaa) alleviates mechanical hypersensitivity in female mice. Mechanistically, ICOSaa treatment promoted mechanical hypersensitivity resolution by increasing interleukin 10 (IL-10) expression in the dorsal root ganglion. Blocking IL-10 receptor activity occluded ICOSaa treatment effects. The findings support a model where ICOSaa administration induces IL-10 expression, facilitating neuropathic pain relief in female mice, suggesting potential development for combination chemotherapy—CIPN clinical trials.

Practical Implications

Potential Therapeutic Target

ICOSaa therapy could be developed for combination chemotherapy—CIPN clinical trials, given its current clinical development for solid tumors and the presence of T cells in the human DRG.

New Mechanism for Pain Resolution

The study demonstrates a new mechanism for stimulating T cells to promote pain resolution via ICOSaa treatment, offering a novel approach to neuropathic pain management.

Sex-Specific Treatment Considerations

The observed sex-specific effects of ICOSaa highlight the importance of considering sex as a biological variable in pain research and treatment strategies.

Study Limitations

1
The study cannot completely rule out a beneficial effect of ICOSaa treatment on male mice.
2
The study has not tested the effect of ICOSaa treatment in mice depleted of T cells or looked at its effect on meningeal T regulatory cells.
3
The study was only done in mice. Replicating this work in another species and using human DRGs will be important to fully understand the translational potential of this novel approach.

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