¹Tokyo Metropolitan Institute of Medical Science, Addictive Substance Project, Tokyo, Japan, ²National Institute of Mental Health, National Center of Neurology and Psychiatry, Department of Neuropsychopharmacology, Tokyo, Japan, ³Tokyo University of Pharmacy and Life Sciences, School of Pharmacy, Tokyo, Japan, ⁴Kitasato University, School of Science, Kanagawa, Japan, ⁵Kobe University, Graduate School of Medicine, Kobe, Japan, ⁶The University of Electro-Communications, Department of Engineering Science, Graduate School of Informatics and Engineering, Tokyo, Japan

Background: Pain remains a significant clinical challenge, especially in chronic and treatment-resistant cases. Current pharmacological options often have limited efficacy and significant side effects, including dependence associated with opioids. FLT3 inhibitors, primarily developed for acute myeloid leukemia, have recently attracted interest for their potential effects on the nervous system. However, their analgesic potential has not been well explored.

Aims & Objectives: ​To evaluate the analgesic effects of a novel FLT3 inhibitor in rodent models of thermal and inflammatory pain using tail flick, hot plate, and formalin tests.

Method: We evaluated the analgesic effects of a newly developed FLT3 inhibitor using established behavioral pain models in rodents: tail flick, hot plate, and formalin tests. Furthermore, we evaluated the analgesic effect of the newly developed FLT3 inhibitor using μ-opioid receptor knockout mice, and confirmed its efficacy in the tail flick and hot plate tests. The newly developed FLT3 inhibitor was administered at a dose of 0.1 mg/kg, and nociceptive responses were assessed at multiple time points post-administration.

Results: In wild-type mice, significant analgesic effects were observed at 60 minutes post-administration in the tail flick and hot plate tests. In the formalin test, analgesic effects became evident from 30 minutes onward, indicating that the compound exerts potent antinociceptive activity in both thermal and inflammatory pain models. In μ-opioid receptor knockout mice, the tail flick latency was significantly prolonged at 30 minutes compared with the saline-treated group. A similar tendency was also observed in the hot plate test.

Discussion & Conclusions: Our findings suggest that the novel FLT3 inhibitor is a promising non-opioid approach for pain management and may also benefit neurodegenerative disorders through effects on neuroinflammation and neuronal maturation.