Differential role of specific cardiovascular neuropeptides in pain regulation: Relevance to cardiovascular diseases.

In many instances, the perception of pain is disproportionate to the strength of the algesic stimulus. Excessive or inadequate pain sensation is frequently observed in cardiovascular diseases, especially in coronary ischemia. The mechanisms responsible for individual differences in the perception of cardiovascular pain are not well recognized. Cardiovascular disorders may provoke pain in multiple ways engaging molecules released locally in the heart due to tissue ischemia, inflammation or cellular stress, and through neurogenic and endocrine mechanisms brought into action by hemodynamic disturbances. Cardiovascular neuropeptides, namely angiotensin II (Ang II), angiotensin-(1-7) [Ang-(1-7)], vasopressin, oxytocin, and orexins belong to this group. Although participation of these peptides in the regulation of circulation and pain has been firmly established, their mutual interaction in the regulation of pain in cardiovascular diseases has not been profoundly analyzed. In the present review we discuss the regulation of the release, and mechanisms of the central and systemic actions of these peptides on the cardiovascular system in the context of their central and peripheral nociceptive (Ang II) and antinociceptive [Ang-(1-7), vasopressin, oxytocin, orexins] properties. We also consider the possibility that they may play a significant role in the modulation of pain in cardiovascular diseases. The rationale for focusing attention on these very compounds was based on the following premises (1) cardiovascular disturbances influence the release of these peptides (2) they regulate vascular tone and cardiac function and can influence the intensity of ischemia - the factor initiating pain signals in the cardiovascular system, (3) they differentially modulate nociception through peripheral and central mechanisms, and their effect strongly depends on specific receptors and site of action. Accordingly, an altered release of these peptides and/or pharmacological blockade of their receptors may have a significant but different impact on individual sensation of pain and comfort of an individual patient.