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Orally consumed cannabinoids provide long-lasting relief of allodynia in a mouse model of chronic neuropathic pain

Edward J.Y. Leung, Antony D. Abraham, Brenden A. Wong, Lauren C. Kruse, Jeremy J. Clark, Benjamin B. Land
doi: https://doi.org/10.1101/556373
Edward J.Y. Leung
1Department of Pharmacology, University of Washington
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Antony D. Abraham
1Department of Pharmacology, University of Washington
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Brenden A. Wong
1Department of Pharmacology, University of Washington
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Lauren C. Kruse
2Department of Psychiatry and Behavioral Sciences, University of Washington
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Jeremy J. Clark
2Department of Psychiatry and Behavioral Sciences, University of Washington
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Benjamin B. Land
1Department of Pharmacology, University of Washington
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  • For correspondence: BBL2@uw.edu
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Abstract

Chronic pain affects a significant percentage of the United States population, and available pain medications like opioids have drawbacks that make long-term use untenable. Cannabinoids show promise in the management of pain, but long-term treatment of pain with cannabinoids has been challenging to implement in preclinical models. We developed a voluntary, gelatin oral self-administration paradigm that allowed animals to consume Δ9-tetrahydrocannabinol, cannabidiol, or morphine ad libitum. Animals stably consumed these gelatins over 3 weeks, with detectable serum levels. We designed a real-time gelatin measurement system, and observed that mice consumed gelatin throughout the light and dark cycles, with THC-gelatin animals consuming less than the other groups. Consumption of all three gelatins reduced measures of allodynia in a chronic, neuropathic sciatic nerve injury model, but tolerance to morphine developed after one week while THC or CBD reduced allodynia over three weeks. Hyperalgesia took longer to develop after sciatic nerve injury, but by the last day of testing THC significantly reduced hyperalgesia responses, with a trend effect of CBD, and no effect of morphine. Mouse vocalizations were recorded throughout the experiment, and mice showed a large increase in ultrasonic, broadband clicks after sciatic nerve injury, which was reversed by both THC and CBD. This study demonstrates that mice will voluntarily consume both cannabinoids and opioids via gelatin, and that cannabinoids can provide long-term relief of chronic pain states. Additionally, ultrasonic clicks may objectively represent the pain status of a mouse and could be integrated into future pain models.

Footnotes

  • ↵* equal authorship

  • Disclosures: The authors have no financial conflicts of interest.

  • Funding These studies were funded by SCAN Design Foundation (Land), and the University of Washington Alcohol and Drug Abuse Institute (ADAI, Small Grants Program) (Land)

Copyright 
The copyright holder for this preprint is the author/funder, who has granted bioRxiv a license to display the preprint in perpetuity. It is made available under a CC-BY-NC-ND 4.0 International license.
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Posted February 21, 2019.
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Orally consumed cannabinoids provide long-lasting relief of allodynia in a mouse model of chronic neuropathic pain
Edward J.Y. Leung, Antony D. Abraham, Brenden A. Wong, Lauren C. Kruse, Jeremy J. Clark, Benjamin B. Land
bioRxiv 556373; doi: https://doi.org/10.1101/556373
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Orally consumed cannabinoids provide long-lasting relief of allodynia in a mouse model of chronic neuropathic pain
Edward J.Y. Leung, Antony D. Abraham, Brenden A. Wong, Lauren C. Kruse, Jeremy J. Clark, Benjamin B. Land
bioRxiv 556373; doi: https://doi.org/10.1101/556373

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