The renin-angiotensin-aldosterone system plays a dual role in pain modulation, with RAAS-blocking drugs showing both pain-relieving effects via anti-inflammatory pathways and pain-inducing actions.
Does modulation of the renin-angiotensin-aldosterone system affect pain perception in different disease states?
This review highlights the complex, dual role of the renin-angiotensin-aldosterone system in pain modulation, suggesting that RAAS-acting cardiovascular drugs may have significant off-target effects on pain perception.
Apart from the well-documented role of the renin-angiotensin-aldosterone system (RAAS) in regulating the blood pressure and other related parameters, its role in modulating different physiological/pathological functions, including pain, has also been described. Like its dual role in regulating stress-related anxiety and cognitive functions, its dual role has also been documented in pain modulation in different disease states. Drugs blocking the RAAS activation, viz., renin inhibitors, angiotensin converting enzyme (ACE) inhibitors, AT(1) receptor antagonists and aldosterone antagonists, have been shown to produce beneficial effects in migraine and neuropathic and nociceptive pain. Their beneficial effects have been mainly attributed to inhibition of the inflammatory cascade of reactions by inhibiting the generation of key cytokines, including tumor necrosis factor (TNF)-α. On the contrary, clinical as well as preclinical studies have also shown the pain-inducing actions of renin-angiotensin system (RAS) blocking drugs. Furthermore, the pain-relieving actions of angiotensin II (AngII) and pain-inducing actions of AT(1) blockers have also been described. The pain-inducing actions of ACE inhibitors have been mainly attributed to interference with metabolism of bradykinin and substance P, while the analgesic actions of AngII have been mainly related to activation of brain localized AT(2) receptors and release of endogenous opioids. The present review describes the dual role of the RAAS in different states of pain.
Bali et al. (2014) conducted a review in Pain (migraine, neuropathic, and nociceptive pain). RAAS blocking drugs (renin inhibitors, ACE inhibitors, AT1 receptor antagonists, aldosterone antagonists) was evaluated. The renin-angiotensin-aldosterone system plays a dual role in pain modulation, with RAAS-blocking drugs showing both pain-relieving effects via anti-inflammatory pathways and pain-inducing actions.