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

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 B-1 and B-2 receptors contribute to chronic painful conditions. Thus, we investigated the involvement of kinins and their B-1 and B-2 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 B-1 and B-2 receptors was investigated using knockout mice or pharmacological antagonism. The protein expression of kinin B-1 and B-2 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 B-1 and B-2 receptor reduced reserpine-induced mechanical allodynia. Antagonism of B-1 and B-2 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 B-1 receptor. Moreover, reserpine increased the protein expression of kinin B-1 and B-2 receptors and levels of kinin, as well as reduced the levels of monoamines in peripheral and central structures. Kinins and its B-1 and B-2 receptors are involved in fibromyalgia-like pain symptoms. B-1 or B-2 receptors might represent a potential target for the relief of fibromyalgia-like pain symptoms.