Exacerbation of paclitaxel-induced neuropathic pain behaviors in breast tumor-bearing mice

Abstract

Background: Chronic pain and cancer interact bidirectionally, with pain enhancing sensory peptides and potentially promoting tumor growth. Despite this, most chemotherapy-induced neuropathic pain (CIPN) studies overlook the contribution of cancer itself to neuropathy, focusing instead on chemotherapy-induced mechanisms. Animal models of chemotherapy-induced neuropathic pain (CINP) have been developed by injecting chemotherapeutic drugs such as paclitaxel into normal animals without cancer. This study aimed to develop a new model in mouse mammary tumor virus-polyomavirus middle T antigen (MMTV-PyMT) mice, a widely used breast cancer model with normal immune function.Results: The percentage of positive response (PPR) of paclitaxel-injected MMTV-PyMT mice increased (about 20%; baseline, 10%) on day 4, reached the highest levels (50%-60%) on days 6-9, and then plateaued by day 29. In comparison, the PPR of paclitaxel-injected C57BL/6 was less than 10% on days 0-6, was about 40% on day 9, and then plateaued by day 29. Breast tumor-bearing mice exhibited an earlier onset and greater severity of paclitaxel-induced pain behaviors than tumor-free C57BL/6 mice. Systemic LGK-974 ameliorated paclitaxel-induced pain behaviors in MMTV-PyMT mice. Active beta-catenin was detected in neurons and satellite cells of the dorsal root ganglia.Conclusions: Paclitaxel-induced neuropathic pain model in breast tumor-bearing female MMTV-PyMT mice may be a useful animal model for investigating the analgesic effects and underlying mechanisms for CINP in breast cancer patients as well as the interplay between CINP development and cancer progression.