Chronic treatment with carboplatin induces mechanical hypersensitivity and neurochemical changes in the mouse dorsal root ganglia and spinal cord.

Purpose: Carboplatin is a widely used antineoplastic drug, but it is associated with severe adverse effects, including peripheral neuropathy. However, the neurobiological mechanisms underlying this side effect are not fully known. Thus, we determined neurochemical changes in the lumbar dorsal root ganglia (DRG) and spinal cord following carboplatin treatment.

Methods: Male BALB/c (23 weeks-old) mice received carboplatin (i.p.; 60 mg/kg/week for 4 weeks) or vehicle. Hindpaw mechanical sensitivity was evaluated at baseline and after carboplatin administration. On day 30 post-first carboplatin administration, mice were euthanized, and the lumbar spinal cord and DRG were processed for immunohistochemistry. Within the L4 DRG, we determined the percentage of neurons expressing the neuropeptide CGRP and the cell injury marker ATF3. Macrophage (CD68, CD163), and blood vessel density (endomucin) were also determined in the DRG. In the spinal cord, we examined the expression of several neuropeptides (CGRP, galanin, NPY) and a marker for astrocyte activation (GFAP).

Results: Carboplatin-treated mice displayed hindpaw mechanical hypersensitivity. The percentage of DRG neurons expressing CGRP and ATF3 as well as the density of CD68⁺ macrophages were significantly greater in carboplatin- compared to vehicle-treated mice. Conversely, the density of CD163⁺ macrophages was significantly reduced in carboplatin- compared to vehicle-treated mice. In the spinal dorsal horn, carboplatin-treated mice showed significantly greater CGRP, galanin, and NPY expression than vehicle-treated mice. There were no changes in the density of endomucin⁺ blood vessels and GFAP immunoreactivity between groups in the DRG and spinal cord, respectively.

Conclusion: Carboplatin induced several neurochemical changes in the mouse DRG and spinal cord, which may contribute to the development of carboplatin-induced peripheral neuropathy.