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Papers of the Week

Papers: 15 Apr 2023 - 21 Apr 2023

Basic Science

Animal Studies, Genetics, Molecular/Cellular, Neurobiology

Cancer Pain, Neuropathic Pain

2023 Apr 03



Novel expression of major histocompatibility complex II in dorsal root ganglion neurons attenuates paclitaxel-induced cold hypersensitivity in male and female mice.


Whitaker EE, Mecum NE, Cott RC, Goode DJ


Chemotherapy is often a life-saving cancer treatment, but the development of intractable pain caused by chemotherapy-induced peripheral neuropathy (CIPN) is a major dose-limiting toxicity that restricts cancer survival rates. Recent reports demonstrate that paclitaxel (PTX) robustly increases anti-inflammatory CD4 T cells in the dorsal root ganglion (DRG), and that T cells and anti-inflammatory cytokines are protective against CIPN. However, the mechanism by which CD4 T cells are activated and the extent cytokines released by CD4 T cells target DRG neurons are unknown. Here, we demonstrate that CD4 T cells can directly contact DRG neurons, and we detected novel expression of functional major histocompatibility complex II (MHCII) protein in DRG neurons, together suggesting direct cell-cell communication and targeted cytokine release. MHCII protein is primarily expressed in small nociceptive neurons in male mouse DRG regardless of PTX treatment, while MHCII protein is induced in small nociceptive neurons in female mice after PTX. Accordingly, eliminating MHCII from small nociceptive neurons significantly increased hypersensitivity to cold temperature in only naïve male mice, while knocking out MHCII in small nociceptive neurons significantly increased the severity of PTX-induced cold hypersensitivity in both female and male mice. Novel expression of MHCII in DRG neurons identifies a targeted mechanism to suppress not only CIPN but also possibly autoimmunity and neurological diseases.