Kinins and their B1 and B2 receptors are involved in fibromyalgia-like pain symptoms in mice

Abstract

Fibromyalgia is a disease characterised as generalised chronic primary pain that causes functional disability and a reduction in patients' quality of life, without specific pathophysiology or appropriate treatment. Previous studies have shown that kinins and their B1 and B2 receptors contribute to chronic painful conditions. Thus, we investigated the involvement of kinins and their B1 and B2 receptors in a fibromyalgia-like pain model induced by reserpine in mice. Nociceptive parameters (mechanical allodynia, cold sensitivity and overt nociception) and behaviours of burrowing, thigmotaxis, and forced swimming were evaluated after reserpine administration in mice. The role of kinin B1 and B2 receptors was investigated using knockout mice or pharmacological antagonism. The protein expression of kinin B1 and B2 receptors and the levels of bradykinin and monoamines were measured in the sciatic nerve, spinal cord and cerebral cortex of the animals. Knockout mice for the kinin B1 and B2 receptor reduced reserpine-induced mechanical allodynia. Antagonism of B1 and B2 receptors also reduced mechanical allodynia, cold sensitivity and overt nociception reserpine-induced. Reserpine altered thigmotaxis, forced swimming and burrowing behaviour in the animals; with the latter being reversed by antagonism of kinin B1 receptor. Moreover, reserpine increased the protein expression of kinin B1 and B2 receptors and levels of kinin, as well as reduced the levels of monoamines in peripheral and central structures. Kinins and its B1 and B2 receptors are involved in fibromyalgia-like pain symptoms. B1 or B2 receptors might represent a potential target for the relief of fibromyalgia-like pain symptoms.