THE RENIN-ANGIOTENSIN SYSTEM AND ITS INVOLVEMENT IN PAIN CONTROL. A NEW INSIGHT INTO AN OLD SYSTEM

Pain is a symptom usually associated with the development of diseases, but it is always a personal experience influenced by contextual, psychological, and social factors. The processing and interpretation of pain include a complicated brain network consisting variety of subordinated structures. At each level of this neural network, numerous cellular processes contribute to the modulation of pain sensitivity. It has been found that the renin-angiotensin system (RAS) plays a significant role in controlling pain under normal and pathological conditions. Recently, new components of the RAS were discovered characterizing two interacting and balancing arms. The classical arm includes the angiotensin-converting enzyme (ACE), the octapeptide angiotensin II (Ang-II), its primary receptor AT1, and the less common AT2 receptor. The alternative arm includes ACE2, the heptapeptide angiotensin 1-7, and its primary receptor Mas-1. RAS has long been known as a homeostasis system primarily responsible for maintaining the physiological balance between the cardiovascular and renal systems. Accumulating data however enlarged scientific knowledge on the role of RAS in control of brain functions and modulation of pain susceptibility. Scientific evidence indicates a differential involvement of angiotensin receptors in the modulation of pain transmission and suppression. Some data seems contradictory, but a thorough analysis emphasized a specific role of receptor distribution and their selective activation/inhibition on the final effect of pain sensitivity. This review summarizes the available literature on the topic and characterizes some perspectives for further research.