Korean J Pain.  2015 Oct;28(4):236-243. 10.3344/kjp.2015.28.4.236.

A New Rat Model of Cisplatin-induced Neuropathic Pain

• Lin H
• Heo BH
• Yoon MH

• KMID: 2151666
• DOI: http://doi.org/10.3344/kjp.2015.28.4.236

Abstract

BACKGROUND
Chemotherapy-induced peripheral neuropathy is a major side effect of anti-cancer drugs, and our knowledge of its mechanisms is lacking. Several models for chemotherapy-induced neuropathy have been introduced. However, the outcomes of these models differ significantly among laboratories. Our object was to create a model of chemotherapy-induced neuropathy in rats with cancer.
METHODS
Female Sprague-Dawley rats were used. Mammary rat metastasis tumor (MRMT-1) cells were implanted subcutaneously in rats. Chemotherapy-induced peripheral neuropathy was induced by injection of cisplatin once a day for four days. The responses to mechanical and thermal stimuli were examined using von Frey filaments, acetone, and radiant heat.
RESULTS
Cisplatin (2 mg/kg/day) produced mechanical allodynia, while it did not induce cold allodynia or thermal hyperalgesia. This dose of cisplatin could work successfully against cancer. Body weight loss was not observed in cisplatin-treated rats, nor were other abnormal behaviors noted in the same rats.
CONCLUSIONS
Repeated injection of intraperitoneal cisplatin induced peripheral neuropathic pain in rats. Thus, this type of rat model has broad applicability in studies related to searching for the mechanism of cisplatin-induced mechanical allodynia and agents for the treatment of neuropathic pain.

Keyword

Chemotherapy; Cisplatin; Models; Neuropathy; Pain; Rats

MeSH Terms

Acetone
Animals
Body Weight
Cisplatin
Drug Therapy
Female
Hot Temperature
Humans
Hyperalgesia
Models, Animal*
Neoplasm Metastasis
Neuralgia*
Peripheral Nervous System Diseases
Rats*
Rats, Sprague-Dawley
Acetone
Cisplatin

Figure

• 

  Fig. 1 Body weight changes were measured after administration of different doses of cisplatin or vehicle (A), MRMT-1 or media injection before cisplatin or vehicle groups (B). Each line represents mean ± SEM. B: baseline body weight before administration of cisplatin or vehicle. *P < 0.05.

• 

  Fig. 2 Hindpaw withdrawal responses to von Frey filaments were measured after administration of different doses of cisplatin or vehicle (A), MRMT-1 or media injection before cisplatin or vehicle groups (B). Each line represents mean ± SEM. B: baseline withdrawal threshold before administration of cisplatin or vehicle. *P < 0.001.

• 

  Fig. 3 Hindpaw withdrawal responses to acetone were measured after administration of different doses of cisplatin or vehicle (A), MRMT-1 or media injection before cisplatin or vehicle groups (B). Each line represents mean ± SEM. B: baseline thermal allodynia before administration of cisplatin.

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  Fig. 4 Hindpaw withdrawal responses to radiant heat were measured after administration of different doses of cisplatin or vehicle (A), MRMT-1 or media injection before cisplatin or vehicle groups (B). Each line represents mean ± SEM. B: baseline thermal hyperalgesia before administration of cisplatin or vehicle.

• 

  Fig. 5 Tumor volumes were measured 15, 21, and 35 days after injection of MRMT-1 cancer cells. Cisplatin or vehicle was injected 15 days after injection of MRMT-1 cancer cells. CIS: cisplatin, VEH: vehicle.

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