Prevention of Allodynia and Hyperalgesia by Cannabidiol in a Rat Model of Chemotherapy-Induced Peripheral Neuropathy

Summary

Co-administration of CBD with paclitaxel prevents the development of chemotherapy-induced peripheral neuropathy in rats. This protocol describes cannabinoid handling, inducing an allodynic phenotype in rats via chemotherapeutic administration, assessing mechanical and thermal allodynia, and using high-speed videography to distinguish allodynia and hyperalgesia.

Abstract

This study demonstrates the utility of a rat model of chemotherapy-induced peripheral neuropathy (CIPN) to assess the ability of the non-psychoactive cannabinoid cannabidiol (CBD) to modulate the development of this syndrome in vivo. The method utilizes the chemotherapeutic agent paclitaxel to generate an allodynic phenotype in the animals. This study describes how to handle and solubilize CBD, administer the chemotherapeutic agent, assess mechanical and cold sensitivity, and apply high-speed videography to measure nocifensive behavior in animals. Using the procedures outlined, the data support that CBD prevents the allodynic phenotype from developing in the treated animals. No difference was observed in the CBD-treated animals from day 0 (pre-paclitaxel baseline) to day 7 (post-sensitization) in mechanical or thermal sensitivity, while the vehicle-treated animals became significantly more sensitive. This response to treatment is durable up to the latest time point where data were collected (7 weeks). The addition of high-speed videography allows for a more granular and unbiased assessment of this behavioral phenotype (e.g., classification of analgesia and anti-allodynia). This demonstrates both the utility of this model for cannabinoid drug characterization and the potential role of CBD in mitigating neuropathic pain.

Introduction

Chemotherapy-induced peripheral neuropathy (CIPN) is a type of sensory neuropathy. It is a common side effect of chemotherapy treatment and is especially prevalent with taxane and platinum-based drugs^1,2. Some symptoms of CIPN include chronic pain, numbness, tingling, and extreme sensitivity to touch and temperature^1,2. These painful symptoms not only interfere with a patient's day-to-day life but also their cancer treatment. Some cancer patients seek a reduction in dosage or a complete termination of chemotherapy to be able to manage the decrease ....

Protocol

This protocol was approved and follows the guidelines of Temple University's Animal Care and Use Committee under approved protocols for animal research. Adult male Sprague-Dawley rats (250-300 g) were used in this study. Details regarding the reagents and equipment used are listed in the Table of Materials.

1. Preparing cannabinoids and chemotherapeutic agents for the induction of CIPN

NOTE: Figure 1 shows the process of solubilization of cannabidiol.

1. Assemble the following materials for solubilization of CBD and dilution of paclitaxe....

Results

The behavioral results elicited by this CIPN model in rats are highly reproducible and consistent. Figure 3A shows baseline and post-paclitaxel sensitization mechanical sensitivity results in control and CBD-treated animals. At baseline, Sprague-Dawley rats generally start to exhibit paw withdrawal at 26-60 g of force as applied by von Frey filaments. This is observable in both treatment groups on day zero. After paclitaxel is administered, vehicle-treated animals become sensitive to the low.......

Discussion

The rat model of chemotherapy-induced peripheral neuropathy recapitulates two of the most reported quality-of-life issues for patients receiving certain types of chemotherapy in mechanical and thermal sensitivity. With this model, relatively inexpensive and efficient methods can quantify these sensitivities via von Frey filament testing and thermal sensitivity through dry ice exposure. This method also provides an additional method for more specialized testing via high-speed videography, which can be us.......

Materials

List of materials used in this article

Name	Company	Catalog Number	Comments
Cannabidiol	Caymen Chemical	90080	Ann Arbor, MI
Chremophor	Millipore-Sigma	238470	St. Lous, MO
Ethanol	Millipore-Sigma	E7023	St. Lous, MO
FastCAM Analysis software	Photon		https://photron.com, open-sourced
High-speed camera	Photron	AX 50
Infrared lights	CMVision	IP65
Normal Saline	Millipore-Sigma	S0817	St. Lous, MO
Paclitaxel	Temple University Hospital Pharmacy	N/A	Philadelphia, PA
Sprague-Dawley rats (250–300 g)	Taconic Laboratories, Cranbury, NJ