EXPRESS: Exacerbation of paclitaxel-induced neuropathic pain behaviors in breast tumor-bearing mice
- Mol Pain. 2025 Sep 5:17448069251380034. doi: 10.1177/17448069251380034.
- 1. Southern Reformed College & Seminary, Houston, TX 77084, USA.
- 2. Department of Physiology, Yonsei University College of Medicine, Seoul 03722, Republic of Korea.
- 3. The Department of Life Science, Chung-Ang University, Seoul, Republic of Korea.
- 4. The Department of Experimental Radiation Oncology, Division of Radiation Oncology; Graduate School of Biomedical Sciences; Program in Genetics and Epigenetics, The University of Texas MD Anderson Cancer Center, Houston, TX 77030, USA.
- 5. University of the Incarnate Word School of Osteopathic Medicine, San Antonio, TX 78235, USA.
- 6. The Department of Pain Medicine, Division of Anesthesiology, Critical Care & Pain Medicine, The University of Texas MD Anderson Cancer Center, Houston, TX 77030, USA.
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 β-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.