Abstract B031: Alternate pain management strategies: targeting pancreatic cancer-related pain with Flavonoid

Abstract

Abstract Purpose 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 (events/5min) was: reduced to 87% of Baseline in tumor-bearing mice, then increased by 150% at 24h post-injection in Group A (FBL-03G); reduced to 65% of Baseline in tumor-bearing mice of Group B, then reduced a further 9% by Vehicle. Dorsal hunching, which events occur only after tumor growth (Baseline =0), was reduced at 24h by 62% in Group A but increased by 75% in Group B. Dorsal twitch, also absent before tumor growth, was reduced by 64% in Group A, but increased by 19% in Group B. Dorsal skin licking was reduced from Baseline by 33% in tumor-bearing mice of Group A, then increased by 76% after FBL-03g injection whereas licking, reduced by 22% by tumors in Group B and then by an additional 4% by vehicle (Group B). Tumors reduced locomotion by 58% in Group A, which was reversed by 32% after FBL-03g (Group A); vehicle injection resulted in a 38% reduction in locomotion (Group B). Thus, in 4 of the 5 pain-related behaviors from tumors quantitated symptoms were reversed by FBL-03G and oppositely affected, or not at all, by Vehicle. Conclusions 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. Citation Format: Sayeda Yasmin-Karim, Suheera Haq, Mike Makrigiorgos, Gary Strichartz, Geraud Richards, Natasha Rayman. Alternate pain management strategies: targeting pancreatic cancer-related pain with Flavonoid [abstract]. In: Proceedings of the AACR Special Conference in Cancer Research: Advances in Pancreatic Cancer Research; 2024 Sep 15-18; Boston, MA. Philadelphia (PA): AACR; Cancer Res 2024;84(17 Suppl_2):Abstract nr B031.