No abstract

Abstract-The cardiovascular system shares numerous anatomic and functional pathways with the antinociceptive network. The aim of this study was to investigate whether angiotensin-converting enzyme (ACE) inhibitor treatment could affect hypertension-related hypalgesia. Twenty-five untreated hypertensive patients, together with a control group of 14 normotensive subjects, underwent dental pain perception evaluation by means of a pulpar test (graded increase of test current applied to healthy teeth). After the evaluation of the dental pain threshold (occurrence of pulp sensation) and tolerance (time when the subjects asked for the test to be stopped), all the subjects underwent a 24-hour ambulatory blood pressure monitoring. The hypertensive group then was treated with 20 mg/d enalapril, whereas the normotensive subjects remained without any treatment. After a time interval of 6Ϯ2 months, the dental pain sensitivity was retested in all the subjects, and ambulatory blood pressure was recorded during treatment in the hypertensive patients. At the first assessment, hypertensive patients showed a higher pain threshold than normotensive subjects (PϽ.001). On retesting of pain sensitivity in hypertensive patients, a significant decrease of both pain threshold and tolerance, leading to their normalization, was observed during treatment (PϽ.001 and PϽ.005, respectively), in the presence of reduced 24-hour and office blood pressure values. A slight, though significant, correlation was observed between variations in pain tolerance and baseline blood pressure changes occurring during treatment. During follow-up, the normotensive subjects did not show any significant pain perception or office blood pressure changes. Hypertension-related hypalgesia was confirmed. Mechanisms acting both through lowering of blood pressure and specific pharmacodynamic properties may account for the normalization of pain sensitivity observed in hypertensive patients during treatment with ACE inhibitors. (Hypertension. 1998;31:1146-1150.)

Both the angiotensin converting enzyme inhibitor enalapril and the AT1 receptor blocking agent losartan acted similarly on pain threshold and tolerance, pain sensitivity being increased during the two anti-hypertensive treatments. The blood pressure reduction during drug assumption could not account for the pain sensitivity changes observed. The latter may be due to a specific pharmacodynamic mechanism mediated through angiotensin II AT1 receptors.

The correlation between both baseline and 24 h blood pressure and pain perception has been confirmed in a large group study of normotensive and hypertensive subjects. Moreover, even among the hypertensive range of blood pressure, the higher the blood pressure is, the lower the sensitivity to pain is. These findings strengthen the hypothesis of a role of the degree of blood pressure elevation in modulating pain sensitivity.

In hypertensive patients, the angiotensin system or bradykinins do not seem to have any modulatory effect on the sympathetic/parasympathetic control of blood pressure and baroreflex sensitivity, in a resting condition. Since heart rates were unchanged by the two antihypertensive treatments despite a significant reduction of blood pressure, a resetting of baroreflex function was observed during both ACE-inhibition and angiotensin II ATI receptor blockade.