Paclitaxel induced-mechanical hypersensitivity is associated with time-dependant pro-inflammatory galectin-3+ macrophages accumulation in the dorsal root ganglia.

Neuropathic pain is a dose-limiting side effect of chemotherapeutic agents such as paclitaxel, and it is unsuccessfully treated by available analgesics. Among the mechanisms underlying paclitaxel-induced neuropathic pain, neuroimmune interactions in the dorsal root ganglia (DRGs) play a pronociceptive role. However, how immune responses evolve over time during pain maintenance and persistence is poorly understood. Here we treated mice with six injections of paclitaxel (PTX) every other day over 10 days (cumulative dose of 15 mg/kg) and detected mechanical hypersensitivity that developed at day 7 and lasted up to day 28 after first PTX injection. We observed a time-dependent accumulation of macrophages in lumbar DRGs at day 28, but not day 14 after first PTX injection. At day 28, proinflammatory macrophages MHCII+CD206- accumulate in DRG together with the emergence of galectin-3 expressing macrophages. Galectin-3 expression was also found in splenic monocytes mirroring the DRG macrophage phenotype and pointing to a coordinated, compartment specific remodelling of innate immune responses. Early adaptive immune responses were spatially and temporally restricted with transient increase in CD8+ T cells in the DRG at day 7 while splenic regulatory T cells were selectively reduced 28 days after first PTX injection. Together these findings reveal that PTX treatment drives coordinated immune responses, and emergence of galectin-3 pro-inflammatory macrophages in DRG could be a feature of persistent paclitaxel-induced neuropathic pain.