Thesis
Cannabinoid antinociception against paclitaxel-induced neuropathic pain in male and female rats
Washington State University
Master of Science (MS), Washington State University
2018
Handle:
https://hdl.handle.net/2376/101305
Abstract
Chemotherapy-induced peripheral neuropathy (CIPN)--a chronic pain condition caused by degeneration of nerve tissue--is a common side-effect of the chemotherapeutics used to treat many types of cancer. CIPN can occur in as many as 68 percent of patients treated with chemotherapeutics and consists of symptoms ranging from mild numbness or tingling in the extremities to severe unrelenting pain. While there are ways to manage the pain once it has developed, the condition is often permanent and there is no approved prophylactic against it. However, preclinical studies have shown that synthetic cannabinoid agonists including WIN 55,212-2 and AM1710 are effective not only in treating the pain associated with CIPN, but also may prevent it. Unfortunately, no synthetic cannabinoids have been approved for human use, however, the naturally occurring phytocannabinoid 9 -tetrahydrocannabinol (THC), in the form of cannabis, is already used to treat chronic pain, including neuropathic pain. The purpose of the present study was to determine the efficacy of THC as a prophylactic against development of CIPN, specifically, against the development of paclitaxel-induced cold and mechanical allodynia in rats. Additionally, this study was designed to investigate sex differences in development and prevention of CIPN. Adult male and female rats were treated on days 1, 3, 5, and 7 with saline or 4.0 mg/kg paclitaxel to induce neuropathy. Concurrently, THC was administered at doses of 0.0, 1.0, 2.0, or 4.0 mg/kg via subcutaneous injection once daily on days 1-9. Rats were tested for mechanical and cold allodynia on days 1, 7, 14, and 21. Unfortunately, paclitaxel did not induce significant cold or mechanical allodynia in male or female rats when compared to saline-treated controls. However, in paclitaxel-treated rats, THC appeared to prevent the reduction in mechanical threshold in males that developed from experimental days 7 to 21. Although THC effects in males are promising, the failure to induce robust allodynia in both males and females limits the conclusions that can be drawn from this study. Possible causes for the observed lack of CIPN are discussed.
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Details
- Title
- Cannabinoid antinociception against paclitaxel-induced neuropathic pain in male and female rats
- Creators
- Hannah Yvonne Gogulski
- Contributors
- Rebecca M. Craft (Degree Supervisor)
- Awarding Institution
- Washington State University
- Academic Unit
- Psychology, Department of
- Theses and Dissertations
- Master of Science (MS), Washington State University
- Publisher
- Washington State University; [Pullman, Washington] :
- Identifiers
- 99900525183401842
- Language
- English
- Resource Type
- Thesis