Vitamin D sufficiency is associated with attenuated paclitaxel-induced nociceptive hypersensitivity and lower endoplasmic reticulum stress-related marker levels in the dorsal root ganglia of aged female mice.

OBJECTIVE

Paclitaxel-induced peripheral neuropathy is frequently accompanied by persistent neuropathic pain. Endoplasmic reticulum stress (ERS)-related responses and neuroinflammation in the dorsal root ganglion (DRG) may contribute to this toxicity. This exploratory study assessed associations between vitamin D status, nociceptive hypersensitivity, and DRG molecular markers in aged female mice.

METHODS

Thirty-two 12-month-old female C57BL/6 mice were assigned to normal control, paclitaxel (PTX), vitamin D-sufficient plus PTX [VD(+) + PTX], or vitamin D-deficient plus PTX [VD(-) + PTX] groups (n = 8/group). Vitamin D sufficiency was established using calcitriol, whereas deficiency was induced using UV-free lighting and a vitamin D-deficient diet. PTX was administered on days 0, 2, 4, and 6. Paw withdrawal threshold (PWT) and latency (PWL) were assessed on days 0, 7, 14, and 21. DRG levels of total IRE1α, CHOP, GRP78, TNF-α, and IL-1β were measured by ELISA on day 21.

RESULTS

PTX produced mechanical and thermal hypersensitivity. Compared with PTX, VD(+) + PTX mice had higher PWT on days 7, 14, and 21 and longer PWL on days 14 and 21. VD(-) + PTX mice showed more persistent hypersensitivity. ERS-related and inflammatory marker levels were lower in VD(+) + PTX mice than in PTX and VD(-) + PTX mice.

CONCLUSION

Vitamin D sufficiency was associated with attenuated PTX-induced nociceptive hypersensitivity and lower DRG levels of ERS-related and inflammatory markers. Because UPR pathway activation and causal mediation were not directly tested, these findings represent exploratory associations rather than evidence of an ERS-mediated analgesic mechanism.