A Modified Inflammatory Pain Model to Study the Analgesic Effect in Mice

Summary

Here, we present a modified inflammatory pain model with the both-hind-paw carrageenan injection to evaluate the analgesic effect.

Abstract

The hot plate test is widely used to evaluate analgesic effects on inflammatory pain in mice. A commonly used model of inflammatory pain was induced with an intraplantar injection of carrageenan in one hind paw. However, the findings from our laboratory showed that mice with a single-hind-paw injection of carrageenan lifted their paws to avoid thermal nociception during the hot plate test. Because of this response, previous injection method cannot accurately reflect the thermal pain threshold. Thus, we investigated a new method to avoid this issue. In the present study, we modified the previous method by injecting carrageenan into both hind paws to establish the model of inflammatory pain. The results demonstrated that both-hind-paw injection with carrageenan was sensitive and a better method to induce inflammatory pain when using the hot plate test than single-hind-paw injection. On the basis of these findings, we designed further experiments in which mice with either both-hind-paw or single-hind-paw injection of carrageenan were treated intragastrically with celecoxib (30 mg/kg). The results of the hot plate test showed that celecoxib augmented the thermal pain threshold in mice with both-hind-paw injection of carrageenan but not in mice with single-hind-paw injection of carrageenan. In summary, we developed a superior method to induce a model of inflammatory pain to evaluate analgesic effect.

Introduction

Pain is a public health problem worldwide. It is triggered by noxious thermal, mechanical, or chemical stimulation. It is difficult to perform pain studies in humans because of ethical concerns. Therefore, using animal pain models is a key approach to understanding pain mechanisms and research treatments¹. The hot plate test has been widely used for the assessment of thermal nociception and hyperalgesia². Currently, the model of inflammatory pain used for the hot plate test is induced with an intraplantar injection of carrageenan in one hind paw. For example, to investigate the antinociceptive effect of rotigotine-loaded....

Protocol

The experimental protocol was approved by the Institutional Animal Care and Use Committee at Yantai University (No. YTDX20220425). The procedures followed the National Institutes of Health Guidelines for the Use of Laboratory Animals.

1. Animals

1. Use ICR female mice weighing 20-25 g for the experiments.
2. Allow the animals to acclimate to the environment of the experimental room for 3 days before starting the experiments.
3. Maintain the experimental room with a 12-h light-dark cycle, and provide the mice with free access to water and chow.

2. Preparation of....

Results

The pain threshold in inflammatory pain models
The pain threshold of the inflammatory pain model with single-hind-paw injection of carrageenan was 32.23 ± 11.11 s, whereas the pain threshold of the control group was 27.73 ± 7.08 s. Compared with the control group, the pain threshold of the single-hind-paw injection model did not show a significant reduction (p > 0.05, Figure 1A). The pain threshold of the inflammatory pain model with both-hind-paw injection of carrage.......

Discussion

Pain is a protective response triggered by tissue damage or injury. However, it also has a negative impact on quality of life¹⁰. Therefore, the development of effective analgesics and exploration of pain mechanisms remain active areas of research. The methods for evaluating pain play a key role in the development of analgesic drugs. Single-hind-paw injection of carrageenan is a classic method for the hot plate test. The modified model induced by both-hind-paw injection of carrageenan we present he.......

Materials

List of materials used in this article

Name	Company	Catalog Number	Comments
AL204 electronic balance	Yuheng Battery Co., Ltd	YH-400A
Carboxymethylcellulose	Tianjin Chemical Co., Ltd	20210326
Carrageenan	Sigma, MO, USA	29H0715
Celecoxib	Pfizer Inc.	8142838
Hot plate	UGO Ltd. Co., Italy	PB-200
ICR female mice	Jinan Pengyue  Co., Ltd.	SCXK20220007
Normal saline	Kelun Pharmaceutical Co., Ltd	H51021157