T Cells Modulate the Development and Maintenance of Painful Paclitaxel-Induced Peripheral Neuropathy in RNU Rats

Authors

Ahmed Olalekan Bakare
Gerard Limerick
Vasudha Goel
Ratan K Banik
Lei Zheng
Andrew J Shepherd
Kristine Glunde
Qin Zheng
Eellan Sivanesan

Language

English

Publication Date

1-1-2026

Journal

Molecular Pain

DOI

10.1177/17448069261418431

PMID

41532412

PMCID

PMC12886724

PubMedCentral® Posted Date

1-14-2026

PubMedCentral® Full Text Version

Post-print

Abstract

The role of T cells in chemotherapy-induced peripheral neuropathy (CIPN) is complex and shaped by biological and experimental factors, including sex, hormonal status, genetic background, and cancer model. This complexity has contributed to inconsistent findings among studies, limiting therapeutic progress. In this study, we investigate how T cells contribute to painful paclitaxel (PTX)-induced peripheral neuropathy (PIPN). Adult male T cell-competent (RNU+/−) and T cell-deficient (RNU−/−) rats were subcutaneously inoculated with tumor cells and subsequently treated with intraperitoneal PTX (8 mg/kg total dose). Reflexive (mechanical, heat, cold) and non-reflexive (burrowing, gait) pain behaviors were assessed from baseline through week 6. Immunohistochemistry (CD68, CX3CR1, CD206) and flow cytometry (CD163, CD86, CD11b/c, CD3, CD161a, CD45RA) were used to assess macrophage and lymphocyte populations. T cell-competent, but not -deficient, rats developed and maintained cold hypersensitivity following PTX. T cells also reduced the onset intensity of PTX-induced mechanical hypersensitivity. In T cell-competent rats, PTX reduced T and B cell counts and increased the CD4+/CD8+ T cell ratio across DRG, sciatic nerve, and spleen. PTX shifted macrophage polarization toward the M1 phenotype and reduced the M2/M1 ratio, independent of T cells. However, M2 macrophages (M2γ and M2a) increased specifically in the sciatic nerves of T cell-deficient rats. Additionally, natural killer (NK) cells decreased in PTX-treated, T cell-deficient rats but remained unchanged in T cell-competent rats. These findings highlight the complex role of T cells in PIPN. In PIPN, T cells play a critical role in driving PTX-induced cold hypersensitivity. A decrease in their number worsens pain intensity, possibly by altering the CD4+/CD8+ T cell balance. In contrast, NK cell reductions in T cell-deficient rats may contribute to hypersensitivity in the absence of T cells.

Keywords

Animals, Paclitaxel, Male, Peripheral Nervous System Diseases, T-Lymphocytes, Rats, Macrophages, Hyperalgesia, Rats, Sprague-Dawley, Chemotherapy-induced peripheral neuropathy, neuropathic pain, paclitaxel, T cells

Published Open-Access

yes

Recommended Citation

Bakare, Ahmed Olalekan; Limerick, Gerard; Goel, Vasudha; et al., "T Cells Modulate the Development and Maintenance of Painful Paclitaxel-Induced Peripheral Neuropathy in RNU Rats" (2026). Faculty, Staff and Student Publications. 6522.
https://digitalcommons.library.tmc.edu/uthgsbs_docs/6522