ABSTRACT
The role of the renin-angiotensin system in human pain is a complicated and controversial field, partly due to the complexities of the system itself, but also because of the diverse ways in which pain functions. Here, we focus on what is known about the angiotensins in pathological pain and describe the ongoing attempts to identify candidate modulators of clinical significance. Systemic angiotensin agonists and antagonists have effects in a number of neuropathic ailments, including some of the most medically intractable conditions, such as endocrine disorders, cancer, myopathies, and viral infections (such as COVID-19), apart from direct damage to the nervous system. These arise due to multiple physiological processes involving both neural and nonneural pathways that could be overcome with future research. In summary, it is clear that the angiotensins acting through their different receptors exercise both algesic and analgesic effects, but less clear how this diversity of responses arises. © 2023 Elsevier Inc. All rights reserved.