Objective: The aim of the project was to determine the analgesic efficacy of locally administered cannabinoids in a rat model of cancer pain. Methods: Prior to starting these behavioral and pharmacological experiments, training was received in OSHA laboratory safety practices, animal handling and conduct, and behavioral testing to determine mechanical paw withdrawal threshold on the plantar surface of the hind paw which is a measure of mechanical allodynia. All rats were subjected to mechanical paw withdrawal threshold (PWT) testing prior to and for five days after implantation of UMR106 osteosarcoma cells unilaterally in and around the calcaneus bone. The drugs used in the completed experiments were ACPA, anandamide, anandamide + AM251, or vehicle (tocrisolve:saline). All of the drugs used were administered locally, via intraplantar injection in the tumor-bearing hind paw in a blinded manner. Different concentrations of the drugs were used to determine if these cannabinoids could attenuate tumor-evoked mechanical allodynia in a dose-dependent manner. Following drug administration, mechanical paw withdrawal thresholds were determined 15, 30, 60, and 180 minutes after drug injection. Results: Before drug injection, the mean mechanical PWT for tumor-bearing animals was 2.21 ±0.156g, and this increased after intraplantar injection of 10ìg (9.43±1.74g, n=4, ANVOA, p<0.001), 1ìg (4.21 ±0.575g, ANOVA, n=4, p<0.001), or 10ng (3.287±0.487g, n=4, ANOVA, p<0.01) of anandamide (AEA). The antihyperalgesia produced by 10ìg AEA was attenuated by co-administration with the CB1 antagonist, AM251 (30ìg) (n=2). Intraplantar injection of vehicle did not produce antihyperalgesia (n=2). Conclusion: The experiments demonstrated the local, peripheral administration of anandamide attenuated tumor-evoked mechanical allodynia in a dose-dependent manner.

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