Demystifying the dual role of the angiotensin system in neuropathic pain

Neuropathic Pain is caused by damage to a nerve or disease of the somatosensory nervous system. Apart from the blood pressure regulating actions of angiotensin ligands, studies have shown that it also modulates neuropathic pain. In the animal models including surgical, chemotherapeutic, and retroviral-induced neuropathic pain, an increase in the levels of angiotensin II has been identified and it has been proposed that an increase in angiotensin II may participate in the induction of neuropathic pain. The pain-inducing actions of the angiotensin system are primarily due to the activation of AT1 and AT2 receptors, which trigger the diverse molecular mechanisms including the induction of neuroinflammation to initiate and maintain the state of neuropathic pain. On the other hand, the pain attenuating action of the angiotensin system has been attributed to decreasing in the levels of Ang(1???7), and Ang IV and an increase in the levels of bradykinin. Ang(1???7) may attenuate neuropathic pain via activation of the spinal Mas receptor. However, the detailed molecular mechanism involved in Ang(1???7) and Ang IV-mediated pain attenuating actions needs to be explored. The present review discusses the dual role of angiotensin ligands in neuropathic pain along with the possible mechanisms involved in inducing or attenuating the state of neuropathic pain.