Background & Aims
Research has shown a small benefit with long term use of cannabis-based medicines in treating various non-cancer chronic pain conditions. Anecdotally, patients with osteoarthritis (OA) report self-medicating with cannabis to treat pain with some benefit. Previous pre-clinical research has been performed on the effects of THC in reducing pain in a mouse model of OA. Results from Von Frey testing in mice who underwent destabilization of the meniscus (DMM) surgery showed reduced mechanical allodynia for mice given high dose(10mg/kg) THC at 9 weeks post surgery compared to mice given the vehicle control. However, in analysing open field behavioral data, there were no differences in locomotion based on administration of THC. Thus, we wanted to investigate the effects of high dose THC on other open field behaviors in a mouse model of OA. Our goal was to determine if there is a difference in open field behavior associated with pain in mice given THC compared to the vehicle control.
Methods
Male C57BL/6 mice either underwent DMM surgery to induce OA or sham surgery as a control. One week after surgery mice were given high dose THC (10 mg/kg) or a vehicle control, medium chain triglyceride via oral gavage. This continued 5 days per week for nine weeks. Open field behavior recording was performed in an open field chamber for 15 minutes using a single overhead camera. Open field behavioral recordings were performed 1 week prior to surgery, 1 week after surgery, 4 weeks after surgery before treatment, 4 weeks after surgery after treatment, 8 weeks after surgery before treatment and 8 weeks after surgery after treatment. The manual open field behavioral analysis was performed using BORIS for each mouse and at time timepoint. The open field behaviors that were quantified were surveying, grooming, walking, rearing, escape and other.
Results
Our results showed that regardless of treatment condition, there is a significant difference in surveying, grooming, walking, rearing and escape behavior over time. Compared to baseline, mice surveyed more at all other timepoints. Mice also groomed more 1 week after surgery compared to baseline. They walked less at all other timepoints compared to baseline. Rearing behavior was reduced at all other time points compared to baseline. At all other timepoints besides 1 week post surgery, mice escaped less than at baseline. Results did not show any effect of treatment either drug given or type of surgery on any of the open field behaviors. However, for grooming behavior, there was a significant treatment-time interaction. At 4 weeks after surgery after treatment, mice in the sham & vehicle condition groomed significantly less than mice in the sham & high dose THC condition. No other significant treatment time interactions were found.
Conclusions
Overtime mice survey more compared to baseline. They also walk, rearing and escape less. This is likely due to aging. When mice underwent DMM surgery, there was no difference in open field behaviors based on administration of THC. However, for mice who underwent sham surgery at 4 weeks after surgery after treatment, mice who received THC groomed significantly more than those who received the vehicle control. These results do not show a significant benefit of THC at reducing pain in OA. Thus, the effects THC of mouse pain behavior are likely limited.
References
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Presenting Author
Lilly Wiersma
Poster Authors
Lilly Wiersma
Leslie Dan Faculty of Pharmacy, University of Toronto
Lead Author
Jason Rockel
PhD
Lead Author
Helena Fetter Filippini
DDS
Lead Author
Anca Maglaviceanu
BSc
Lead Author
Ewa Wasilewski
MSc
Lead Author
Melissa Lewis-Bakker
MSc
Lead Author
Sarah Gabrial
BSc
Lead Author
Johana Garcia
Lead Author
Timothy Leroux
MD
Lead Author
Hance Clarke
MD
University Health Network, University of Toronto
Lead Author
Lakshmi Kotra
B.Pharm.(Hons)
Lead Author
Mohit Kappor
PhD
Lead Author
Robert Bonin
PhD
University of Toronto
Lead Author
Topics
- Treatment/Management: Cannabinoids and Cannabis