Renin-Angiotensin-Aldosterone System: A Current Drug Target for the Management of Neuropathic Pain

Renin-Angiotensin-Aldosterone System (RAAS) is well established in renovascular and cardiovascular functions. The modulators of this system are significantly used for regulating elevated blood pressure in human and animals. Recently, it has also been documented to produce neurological actions. The abnormalities of this system raise renin, angiotensin (AT), angiotensin converting enzyme (ACE) activity, and aldosterone in circulation and nerve tissues. In the nervous system, abundant rise of these components cause neuronal damage and neurodegeneration. ACE contributes to degradation of beta-amyloid in the brain, that is responsible for Alzheimer disease (AD). But, angiotensin converting enzyme-2 (ACE-2) mediated release of angiotensin(1-7) (AT(1-7)) peptide in nerve tissue has potential neuroprotective actions. This review focuses on the current perspectives of the RAAS in neurodegeneration along with possible cellular and molecular mechanisms. Also, we have discussed the current evidence of RAAS modulators in the management of neuropathic pain in human and animals. Thus, we believe that, in the future, RAAS modulators may play a great role in the management of neuropathic pain and other neurodegenerative disorders such as AD, Parkinson disease (PD) and amyotrophic lateral sclerosis. But, more extensive clinical research is required for utilizing RAAS modulators in neurodegenerative disorders.