Honors Theses

Date of Award

Spring 5-9-2026

Document Type

Undergraduate Thesis

Department

Biomolecular Sciences

First Advisor

Nicole M. Ashpole

Second Advisor

Gregg Roman

Third Advisor

Kristine Willett

Relational Format

Dissertation/Thesis

Abstract

Chemotherapy is the predominant treatment for a variety of cancers, but throughout its history of use, many side effects have been reported. One of the most common side effects is chemotherapy-induced peripheral neuropathy (CIPN). This side effect subjects an estimated 60% of patients to pain for months to years following chemotherapy. This symptomology is due tothe upregulation of ion channels such as TRPV1, which leads to the release of TNF-α, causing inflammation. These changes manifest in the intraepidermal nerve fibers (IENF), in which chemotherapy damages nociceptors, leading to an overall reduction in density. Current therapeutics, historically limited to opioids or other analgesics, are associated with additional adverse effects, most notably the potential for abuse. Therefore, there is a necessity to develop more effective treatments with fewer risks.

In recent years, cannabinoids have emerged as an alternative to analgesics. Our previous research has shown that cannabichromene (CBC), a minor phytocannabinoid, is capable of alleviating multiple types of pain, while also being devoid of the psychoactive properties of other cannabinoids or the abuse potential of opioids. Given these properties, it was a suitable candidate for assessment against CIPN. We found through the utilization of CIPN mouse models, that CBC was able to attenuate the mechanical sensitivity caused by cisplatin (i.e., mice treated with CBC were less sensitive to mechanical stimulation). While this data provided insightful behavioral outcomes, the cellular mechanisms for this mitigation of CIPN remained unexplored.

As a result, the present study aims to elucidate the specific mechanisms through which CBC mitigates CIPN through optimization of protocols and experimental methods. Hind paws were collected from 6–8-week-old male and female C57BL/6J mice treated with cisplatin (2.3 mg/kg, 6 doses) and vehicle, or cisplatin and CBC (25 mg/kg, single dose). Immunohistochemistry staining protocols were utilized to determine intraepidermal nerve fiber (IENF) density by staining for PGP 9.5 in the hind paws. The acute administration of CBC in male mice that were treated with cisplatin chemotherapy did not show any significant differences in IENF density or in cytokine activation, indicating the possibility for different mechanisms by which CBC attenuates pain.

Creative Commons License

Creative Commons Attribution-NonCommercial 4.0 International License
This work is licensed under a Creative Commons Attribution-NonCommercial 4.0 International License

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