How do the angiontensin II type 2 receptors modulate pain, and what clinical evidence exists for pain modulation?
Angiotensin II is a potent vasopressor hormone important in controlling blood pressure and volume in the cardiovascular system. It binds and stimulates at least two types of receptors: AT1 and AT2. AT2 is a G-protein-coupled receptor that plays a role in CNS function. AT2 receptors are expressed on small diameter nerve fibers and dorsal root ganglion cells. Angiotensin converting enzyme (ACE) converts angiotensin I to angiotensin II. However, studies on ACE inhibitors have failed to show an effect on pain. Therefore, AT2 receptor antagonists have been developed for pain relief. A phase II study in postherpetic neuralgia randomized 183 patients to placebo or an AT2 receptor antagonist (EMA-401). The study met the primary endpoint of reduction in pain intensity. Secondary outcomes of onset, 30%/50% responder rate, McGill and Patient Global Impression of change were also met. The drug was safe and well tolerated.