Altered sensitivity to mechanical stimulation during prolonged subcutaneous administration of endothelin-1 in rats

Guy Hans^1,2,3, Kristof Deseure^2,3, Marcel Vercauteren^1,2,3

¹Multidisciplinary Pain Center; ²Department of Anesthesiology, Antwerp University Hospital, Edegem, Belgium; ³Laboratory of Anesthesiology and Pain Research, University of Antwerp, Wilrijk, Belgium

Abstract: Cancer pain is often difficult to treat. Growing evidence indicates that chemical mediators secreted by the tumor itself play an important role in the development of cancer pain. One such mediator, endothelin-1 (ET-1) is secreted by different tumor types. Studies have indicated that ET-1 induces spontaneous and evoked nociception in rodents and in humans. The focus of all these studies has always been on a single administration of ET-1. Such an acute exposure to ET-1 however bears little resemblance to the clinical condition in which cancer patients are exposed continuously for many months to increased levels of ET-1. To improve the knowledge of the pathological role of ET-1 in cancer, we developed an animal model of prolonged exposure to ET-1. Rats were exposed to subcutaneous administration of ET-1 for seven consecutive days, with a total amount of 67.4 nmol. On days +2, +3, +5, +7, and +10 sensitivity to von Frey hairs and to pin-prick stimulation were evaluated. Prolonged administration of ET-1 induced signs of mechanical allodynia on several time points. Although the administered doses were very small, prolonged administration of ET-1 seems to lead to a state of mechanical allodynia.

Keywords: endothelin-1, rat, chronic administration, von Frey hair, pin-prick, mechanical allodynia