Purpose: Paclitaxel (PTX) is a typical anticancer drug that induces peripheral neuropathy and significantly reduces patients' quality of life. Previous our study showed gabapentinoids, such as mirogabalin, attenuate PTX-induced peripheral neuropathic pain by acting on the spinal dorsal horn. PTX-induced peripheral neuropathy has so far focused on peripheral inflammation, but it is possible that changes in the spinal dorsal horn may contribute to PTX-induced peripheral neuropathy. In this study, we investigated the mechanism of synaptic plasticity in the spinal dorsal horn by using electrophysiological and immunohistochemical analysis.
Methods: We administered a single intraperitoneal dose of PTX 5 mg/kg to C57BL/6NCr mice.　We analyzed the frequency of spontaneous and von Frey filament (vFF; 0.69 mN) evoked firing in spinal dorsal horn neurons by using in vivo extracellular recording. Immunohistochemical staining was performed on spinal cord (L4-6) slices.
Results: Electrophsiological data showed the frequency of spontaneous and vFF evoked firing in spinal dorsal horn neurons were significantly enhanced in PTX model mice.
The levels of the neuronal activation marker c-fos were increased with mechanical allodynia formation in PTX model mice. Glia-associated makers Iba1 and GFAP also showed chronological changes after PTX-treatment.　
Conclusion: The present study suggests that synaptic plastic changes occur not only in the periphery but also in the spinal dorsal horn in the PTX-induced peripheral neuropathic pain model.