ABS 013: Alternate pain management strategies: targeting pancreatic cancer-related pain with Flavonoid

Suheera Haq ¹, Sayeda Yasmin-Karim ² ³, Geraud Richard ² ³, G. Mike Makrigiorgos ² ³, Gary Strichartz ³ ⁴, Natasha N. Rayman ⁵

¹ Department of Molecular and Cell Biology, University of Connecticut, Storrs, Connecticut
² Department of Radiation Oncology, Brigham and Women’s Hospital and Dana-Farber Cancer Institute
³ Harvard Medical School, Boston,Massachusetts, USA
⁴ Department of Anesthesia, Brigham and Women’s Hospital and Harvard Medical School, Boston, Massachusetts, USA
⁵ Department of Gender Studies, Queen’s University, Kingston, Canada

Van Wickle (2025) Volume 1, ABS013

Introduction: For up to 90% of cancer patients, pain is a substantial symptom, contributing to morbidity and, possibly, mortality. In this study we sought to test the hypothesis that a flavonoid, derived from Cannabis, and previously shown to suppress cancer cell growth in vitro and tumor progression in mice in vivo, could also reduce the pain caused by pancreatic tumors in vivo.

Methods: A subcutaneous tumor in the dorsum of C57BL/6 mouse was generated by sub-dermal injection of KPC mouse pancreatic cancer cell line (ATCC). All the mice were video recorded to observe and analyze their spontaneous pain-related behaviors, including facial washing, dorsal hunching, dorsal skin twitch, licking of dorsal skin and overall locomotion around the cage. Two five minute recording sessions were analyzed by a blinded observer during times before the cancer cell injection (Baseline), after tumor growth, to about 8mm diameter (30d and 37d post-injection) and just before and then 24h after intra-tumor injection of the flavonoid ( Group A: FBL-03G, 1 nmole in 100µL) or Vehicle(100µL; Group B). Pain-related behavioral changes were averaged from the two recording sessions and analyzed from Baseline, just before FBL-03G and 24h after and compared between test compound-and vehicle injected groups (n=7 in each), using non-parametric statistics.

Results: Facial washing was reduced to 87% of baseline in tumor-bearing mice, then increased by 150% after FBL-03G (Group A), but fell to 65% and declined further with Vehicle (Group B). Dorsal hunching and twitching, absent at baseline, were reduced by 62% and 64% respectively in Group A, but increased by 75% and 19% in Group B. Dorsal skin licking dropped 33% in Group A, then rose 76% post-FBL-03G; in Group B, it declined slightly after tumors and vehicle. Tumor growth reduced locomotion by 58% in Group A, partially reversed by FBL-03G (32% increase), while locomotion dropped further by 38% with Vehicle (Group B). Overall, FBL-03G reversed tumor-induced pain behaviors in 4 of 5 measures, unlike Vehicle.

Discussion: These results indicate a substantial relief of spontaneous pain-related pain in this mouse model of pancreatic cancer. Such an acute effect occurs much more rapidly than the previously published in vitro suppression of KPC cell growth (assayed after 9-12d of treatment) or the reduction of tumor size (1-7 weeks) in vivo and suggest that the anti-hyperalgesic affect is due to mechanisms that do not involve reduction in tumor mass. The findings, using a single dose and a small number of mice, appear promising for further studies that examine a range of doses or FBL-03G and its actions in intra-pancreatic tumors.