Curcumin analog C16 attenuates bone cancer pain induced by MADB 106 breast cancer cells in female rats and inhibits the CREB/NLGN2 signaling axis by targeting CaMKⅠα.

Bone cancer pain (BCP) is one of the most severe complications faced by patients with cancer; however, current pharmacological options are limited. Curcumin has been demonstrated to possess anti-inflammatory and analgesic properties; however, our preliminary research found that the analgesic efficiency of curcumin is not high in BCP. Consequently, curcumin analogs have emerged as a significant focus of our research. This study aimed to systematically investigate the analgesic effects of C16 in rats with BCP induced by MADB 106 breast cancer cells (MADB 106-induced BCP) and elucidate the underlying molecular mechanisms. A range of experimental methods, including kinase profiling, transcriptome sequencing, behavioral tests, immunofluorescence, and biochemical analyses, were employed to comprehensively assess the role of C16 in the MADB 106-induced BCP model. The results indicated that C16 significantly alleviated bone cancer pain induced by Luciferin-MADB 106 cells (10ˆ6 cells) in a dose-dependent manner. Importantly, kinase profiling and validation experiments identified CaMKIα in spinal dorsal horn neurons as the primary target of C16's analgesic effect on MADB 106-induced BCP. Continuous intrathecal administration of C16 markedly suppressed the expression of CREB and P-CREB and reduced the expression of neuroligin 2 in the spinal cords of BCP rats, thereby clarifying the mechanism of action of C16 in alleviating MADB 106-induced BCP. These findings suggest that C16 possesses significant therapeutic potential for mitigating MADB 106-induced BCP nociceptive hypersensitivity, providing a foundation for the future development of novel drugs targeting MADB 106-induced BCP. This article is part of the Special Issue on "Empathic Pain". [Display omitted] • 1. Intrathecal administration of C16 significantly relieves bone cancer pain in rats via targeting CaMKⅠα. • 2. Intrathecal administration of C16 notably improves pain-related negative emotions in rats with bone cancer pain. • 3. C16 alleviates bone cancer pain by modulating CREB/NLGN2 signaling pathway. [ABSTRACT FROM AUTHOR]