Treatment with enalapril modifies the pain perception pattern in hypertensive patients.

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 6+/-2 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 (P<.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 (P<.001 and P<.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.

Relationship between dental pain perception and 24 hour ambulatory blood pressure: a study on 181 subjects.

OBJECTIVE: To investigate dental pain perception in a large group of essential hypertensive subjects. METHODS: A total of 130 hypertensive patients together with 51 normotensive subjects were submitted to tooth-electrical stimulation to determine the dental pain threshold (occurrence of pulp sensation) and tolerance (time when the subject asked for the test to be stopped). Blood pressure was measured at rest, before pain perception evaluation, and during a 24 h period by ambulatory monitoring. RESULTS: The normotensive and hypertensive subjects differed with regard to pain threshold (P = 0.002) and tolerance (P = 0.01). Pain perception variables were significantly correlated with both resting blood pressure and 24 h, diurnal and nocturnal arterial pressures, the correlation between pain threshold and 24 h systolic blood pressure being the most significant (r = 0.31, P < 0.0001). By contrast, parameters indicating 24 h blood pressure variability (percentage of nocturnal blood pressure reduction and 24 h blood pressure variation coefficients) were not associated with pain perception. Moreover, among the hypertensives only, a significant relationship was observed between pain sensitivity and both baseline and 24 h pressures. No association was found when pain perception and blood pressure were correlated in the normotensive group. CONCLUSIONS: 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.

Hepatitis C antibody and cryoglobulins in patients with cirrhosis and hepatocellular carcinoma.

OBJECTIVE: To assess: (1) the role of hepatitis C virus (HCV), hepatitis B virus (HBV) and alcoholism as risk factors for hepatocarcinoma (HCC) in patients with liver cirrhosis, and (2) the presence of cryoglobulins in HCV + patients with and without HCC. PATIENTS: 82 cirrhotic patients, 41 with and 41 without HCC, who were admitted consecutively to our General Medicine Division from January 1992 to June 1994, were studied. RESULTS: The prevalence of HBV markers, anti-HCV and alcoholism in patients with liver cirrhosis and HCC was 39%, 63.4% and 24%, and in cirrhotics without HCC it was 31.7%, 51.2% and 63.4%, respectively. Cryoglobulins were present in 87.5% of the patients with HCC (78.5% anti-HCV +) and in 57.8% of the patients without HCC (81.8% anti-HCV +). The cryoglobulins, as characterized in 11 cases, were type III in nine cases and type II in two. CONCLUSIONS: Patients with cirrhosis, especially when associated with HCV and HBV infection, are at high risk for HCC and therefore require careful follow-up. Moreover, a strong association between HCV and the cryoglobulins in cirrhotics with and without HCC was evident, thus supporting the possible role of this virus in stimulating lymphocytes to produce cryoglobulins.

Colchicine in the treatment of mixed cryoglobulinemia.

OBJECTIVE: The best treatment for cryoglobulinemic syndrome (CS) is still an unsolved problem. Recently colchicine has been successfully used to treat vasculitides and other immune-mediated diseases. Therefore, we undertook to treat 17 CS patients with colchicine (1 mg/day for 6-48 months), 8 of them with essential mixed cryoglobulinemia (EMC) and 9 with CS secondary to liver disease. METHODS: In all patients the clinical and laboratory features were evaluated at the beginning of the study and during the first 6-12 months; 10 cases were followed for a longer period (18-48 months). RESULTS: During the first period symptoms improved as follows: purpura in 15 of 17 patients, weakness in 9 of 14 and leg ulcers in 3 of 5. Hepatic and renal function tests, hypocomplementemia, rheumatoid factor (RF) titres and the cryocrit also improved. Prolonged follow-up showed a relapse in the different variables, although they remained at better levels than at the beginning. Only the cryocrit showed a further reduction. CONCLUSION: Though this was a preliminary open study it shows that colchicine is an efficient treatment in CS and suggests that a controlled clinical study should be performed to assess its real value.

Autonomic function and baroreflex sensitivity during angiotensin-converting enzyme inhibition or angiotensin II AT-1 receptor blockade in essential hypertensive patients.

OBJECTIVE: The influence of ACE-inhibition and angiotensin II ATI receptor blockade on the autonomic function and baroreflex sensitivity was investigated in hypertension. METHODS AND RESULTS: Heart rate variability was assessed in a resting condition by power spectrum analysis to evaluate the low frequency (LF) power, high frequency (HF) power and LF/HF ratio in 19 hypertensive patients and 23 normotensive controls. Moreover, the coherence between the tachogram and the systogram was evaluated, and the baroreflex gain (alphaLF-index), describing the transfer function of variability in the systolic pressure signal to variability in the RR interval, was obtained. Then a 24-h ambulatory blood pressure monitoring was performed. The 19 hypertensive patients were randomized to either enalapril or losartan treatment, and after 2 months were re-submitted to the RR variability and baroreflex study and to blood pressure monitoring. The subjects then crossed to the other antihypertensive treatment and were re-evaluated after an additional two months. No significant difference was found either in LF power and HF power and LF/HF ratio between normotensive and hypertensive subjects whereas a slight though significant difference was observed in the alphaLF-index. In hypertensive patients, both the treatments with enalapril and losartan reduced blood pressure and had no effect on heart rate. No significant change was observed in autonomic balance or in baroreflex sensitivity during the two antihypertensive treatments. CONCLUSIONS: 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.

Autonomic function and baroreflex sensitivity during a normal ovulatory cycle in humans.

OBJECTIVE AND DESIGN: Possible variations occurring in the autonomic function during a normal ovulatory cycle have been poorly investigated and it is not known whether the baroreflex sensitivity may change according to the different phases of the cycle. The aim of this study was to evaluate heart rate variability (power spectrum analysis), and baroreceptor sensitivity (alpha-low frequency coefficient) in 13 young women with regular menses during the two phases of the cycle (phase I: 5 +/- 1 days and phase II: 23 +/- 3 days from bleeding). RESULTS: The low frequency/high frequency ratio was significantly higher in the second phase of the cycle (phase I: 2.8 +/- 2.6; phase II: 5.6 +/- 5.8, p < 0.05), in the presence of increased low frequency and reduced high frequency expressed in normalized units-nu-(phase I: 59.8 +/- 16.7 nu and 32.6 +/- 15.6 nu for low frequency and high frequency, respectively; phase II: 67.7 +/- 18 nu and 25.7 +/- 17.5 nu for low frequency and high frequency, respectively; p < 0.05). The alpha-low frequency coefficient, index of baroreflex sensitivity, did not statistically differ in the two phases (phase I: 10.6 +/- 4.5 msec/mm Hg; phase II: 8.9 +/- 4.9 msec/mm Hg; ns). CONCLUSIONS: The power spectrum analysis suggests that the autonomic function may be affected by the ovulatory cycle, sympathetic activation being relatively increased in the second phase. On the contrary, the baroreceptor function seems to be scarcely influenced by the two phases of the menstrual cycle.