Blockade of peripheral endothelin receptors abolishes heat hyperalgesia and spontaneous nociceptive behavior in a rat model of facial cancer

Publication date: Available online 2 November 2018

Source: Archives of Oral Biology

Author(s): Caroline Machado Kopruszinski, Renata Cristiane dos Reis, Giles Alexander Rae, Juliana Geremias Chichorro

Abstract

Objective

To improve understanding of the pathophysiology of cancer-induced facial nociception, by evaluating the contribution of peripheral endothelin receptors in tumor-induced facial heat hyperalgesia, increased spontaneous grooming, as well as ongoing nociception in a rat model of facial cancer.

Design

The study was conducted using 396 rats. Facial cancer was induced by inoculating a suspension of Walker-256 cells into the rats' right vibrissal pad. Facial heat hyperalgesia and spontaneous grooming were assessed on day 6, while the conditioned place preference (CPP) test was performed on days 3 to 6 after tumor cells inoculation. Rats received local injections of the non-peptidic dual ET_A/ET_B endothelin receptors antagonist, bosentan (10 and 30 µg/50 µL), single or combined injections of peptidic ET_A and ET_B endothelin receptors antagonists (BQ-123 and BQ-788, at 20 ug/50 µL, each), or of lidocaine (1 mg/50 µl) and morphine (30 µg/50 µL).

Results

Bosentan, lidocaine and morphine local treatment all attenuated tumor-induced heat hyperalgesia (p < 0.05) and spontaneous facial grooming (p < 0.05). However, BQ-123 and BQ-788 did not modify tumor-induced heat hyperalgesia or the spontaneous facial grooming (p > 0.05). Whether this difference in effectiveness is due to receptor affinity or to pharmacokinetic factors still needs to be explored. Local injection of bosentan, lidocaine or morphine failed to control ongoing nociception, as evidenced by the absence of CPP in tumor-bearing rats (p > 0.05).

Conclusion

Endothelins, acting through peripheral ET_A and ET_B receptors, may play a significant role on the development of heat hyperalgesia and increased spontaneous grooming associated to facial cancer in rats.

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