Vagus nerve stimulation attenuates heat- and formalin-induced pain in rats.

The analgesic effect of vagus nerve stimulation (VNS) has not yet been demonstrated in animals with the devices used in the clinic. We studied in awake rats the effects of two VNS protocols on the hind paw hot water test and compared the results with those previously obtained in the oro-facial formalin test. A stringent duty cycle (20 s on/18 s off) increased heat pain tolerance in both hind paws (average 188%) after 2 h of stimulation. VNS with parameters used in epilepsy (30 s on/5 min off) decreased heat tolerance after 2 h, but produced a significant antinociceptive effect after days of stimulation. VNS may thus be useful in pain disorders, even with the less stringent protocol.

Excitability of visual V1-V2 and motor cortices to single transcranial magnetic stimuli in migraine: a reappraisal using a figure-of-eight coil.

We used transcranial magnetic stimulation (TMS) with a figure-of-eight coil to excite motor and visual V1-V2 cortices in patients suffering from migraine without (MO) (n = 24) or with aura (MA) (n = 13) and in healthy volunteers (HV) (n = 33). Patients who had a migraine attack within 3 days before or after the recordings were excluded. All females were recorded at mid-cycle. Single TMS pulses over the occipital cortex elicited phosphenes in 64% of HV, 63% of MO and 69% of MA patients. Compared with HV, the phosphene threshold was significantly increased in MO (P = 0.001) and in MA (P = 0.007), but there was no difference between the two groups of migraineurs. The motor threshold tended to be higher in both migraine groups than in HV, but the differences were not significant. In conclusion, this study shows that two-thirds (64.86%) of patients affected by either migraine type present an increased phosphene threshold in the interictal period, which suggests that their visual cortex is hypoexcitable.

Vagus nerve stimulation in awake rats reduces formalin-induced nociceptive behaviour and fos-immunoreactivity in trigeminal nucleus caudalis.

Besides its well-established efficacy in epilepsy, vagus nerve stimulation (VNS) may be of potential interest in pain treatment. It has, however, not yet been assessed in animal pain models with the devices and stimulation protocols used in humans. We have therefore studied in awake rats the effects of left cervical VNS on trigeminal nociception using an implantable electrode and stimulator (NCP-Cyberonics). VNS was applied for 24h at 2 mA intensity, 20 Hz frequency, 0.5 ms pulse width and a duty cycle of 20s ON/18s OFF. As a nociceptive stimulus, we injected formalin into the left mystacial vibrissae, assessed behaviour for 45 min and sacrificed the animals 45 min later. Fos-immunoreactive (Fos-Ir) neurons were counted in laminae I-II of trigeminal nucleus caudalis (TNC) on both sides. We used three groups of control animals: VNS without formalin, formalin without VNS and sham VNS (implanted without stimulation or formalin). Whereas sham VNS had no significant effect, VNS alone increased Fos expression in ipsilateral TNC in addition to the expected increase in nucleus tractus solitarius. It also significantly attenuated the increase of Fos-Ir neurons observed in ipsilateral TNC laminae I-II after formalin injection. If the proper VNS effect on Fos-expression was subtracted, the reduction of formalin-induced nociceptor activation was 55%. VNS also reduced nociceptive behaviour on average by 96.1% during the early phase (0-6 min) and by 60.7% during the late phase (6-45 min) after the formalin injection. These results suggest that VNS applied with a device used in human therapy may have in awake rats a significant antinociceptive effect in a model of trigeminal pain.

Effects of repetitive transcranial magnetic stimulation on visual evoked potentials in migraine.

Between attacks, migraine patients are characterized by potentiation instead of habituation of stimulation-evoked cortical responses. It is debated whether this is due to increased or decreased cortical excitability. We have studied the changes in visual cortex excitability by recording pattern-reversal visual evoked potentials (PR-VEP) after low- and high-frequency repetitive transcranial magnetic stimulation (rTMS), known respectively for their inhibitory and excitatory effect on the cortex. In 30 patients (20 migraine without, 10 with aura) and 24 healthy volunteers, rTMS of the occipital cortex was performed with a focal figure-of-eight magnetic coil (Magstim). Nine hundred pulses were delivered randomly at 1 or 10 Hz in two separate sessions. Stimulus intensity was set to the phosphene threshold or to 110% of the motor threshold if no phosphenes were elicited. Before and after rTMS, PR-VEP were averaged sequentially in six blocks of 100zztieresponses during uninterrupted 3.1 Hz stimulation. In healthy volunteers, PR-VEP amplitude was significantly decreased in the first block after 1 Hz rTMS and the habituation normally found in successive blocks after sustained stimulation was significantly attenuated. In migraine patients, 10 Hz rTMS was followed by a significant increase of first block PR-VEP amplitude and by a reversal to normal habituation of the potentiation (or dishabituation) characteristic of the disorder. This effect was similar in both forms of migraine and lasted for at least 9 min. There were no significant changes of PR-VEP amplitudes after 1 Hz rTMS in migraineurs and after 10 Hz rTMS in healthy volunteers, nor after sham stimulation. The recovery of a normal PR-VEP habituation pattern after high-frequency rTMS is probably due to activation of the visual cortex and the dishabituation in healthy volunteers to cortical inhibition. We conclude, therefore, that the deficient interictal PR-VEP habituation in migraine is due to a reduced, and not to an increased, pre-activation excitability level of the visual cortex.

Hepatic artery hemodynamics in acute viral hepatitis.

In order to evaluate the effect of the acute viral hepatitis on arterial blood flow we performed duplex Doppler US on 30 patients with acute viral hepatitis (AVH) and compared the results with those obtained on 20 normal volunteers. Hepatic artery flow (HAF) was significantly increased with the patients suffering from acute viral hepatitis. The data obtained show that the increase of arterial blood flow is not always associated with the increase of arterial velocities. We could put in evidence the presence of the hepatic artery response to altered portal blood flow (arterial buffer) during a AVH. If the increase of HAF is absolutely necessary for recovery from hepatitis, excessive increase of HAF seems to increase the time of recovery. In our study, the evolution of acute viral hepatitis was good when the HAF values did not exceed 65% of liver supply. The increase of arterial blood flow over 65% seems to limit the portal supply of the liver and in this way the amounts of regenerating substances which bathe the liver cells. The HAF value plays an important role in acute viral hepatitis evolution, so that the exploration of HAF and hepatic artery velocities may be a reliable examination in order to monitor the evolution of this disease.

The diminution of platelet activity in vitamin E-treated diabetic rats.

BACKGROUND: Because vitamin E deficiency has been demonstrated in platelets obtained from diabetic subjects, in our research we investigated the platelet activity and the oxidative stress in alloxan diabetic rats supplemented with vitamin E. MATERIAL AND METHODS: The platelet activity was estimated by the adhesion index (AI) and the oxidative stress was correlated with the determined level of malondialdehyde (MDA) an end product of lipid peroxidation. RESULTS: We found that alloxanic diabetes was associated with significant increase in the both MDA level and AI (p < 0.01 and p < 0.05, respectively). The AI was better correlated to the MDA level (r = +0.60) than to the hyperglycemia. The administration of vitamin E before and after alloxan was accompanied by a significant decrease of both MDA level and AI comparing to untreated diabetic rats. CONCLUSIONS: Our study suggests that vitamin E supplementation may improve the increased platelet adhesion as a consequence of an increased oxidative stress and therefore the incidence of diabetic angiopathy may be reduced.

[The reduction of dyslipidemia and oxidative stress in experimental diabetes mellitus treated with probucol]. / Reducerera dislipidemiei si a stressului oxidativ în diabetul zaharat experimental tratat cu probucol.

There is considerable controversy regarding the role of oxidative stress in development of macro and microangiopathy in diabetes--a free radical associated disease. Increasing the oxidative glycosylation of plasma lipoproteins by reactive oxygen species (ROS) and reduction of scavenging system under conditions of hyperglycemia may accelerate diabetic vascular disease. We have investigated the effect of Probucol (P) a drug with strong lipophilic radical scavenger action, on plasma lipoproteins variations, malondialdehid (MDA) production, atherosclerotic index (total Cholesterol/HDL Cholesterol), glycemia and glucosuria in Wistar male alloxanic rats with/without enriched cholesterol diet. The inhibition of lipoproteins oxidation, resulting from diminishing MDA, in our study, would furthermore delay the absorption and penetration of lipids and lipoproteins into deeper vascular layers and thereby reduce the risk of atherosclerotic vascular lesion. Our result suggest that treatment with inhibitors of lipoproteins oxidation may reduce the risk of cardiovascular complications in diabetes.

The relation zinc-lipidic peroxidation in experimental diabetes mellitus.

The authors investigated the influence of Zn upon glycemy and certain REDOX parametres within the hepatic tissue. The experiment was performed on young Wistar rats with AD, to which Zn sulfate was administered. The values of the antioxidating enzymes: cathalasis and peroxidase decrease in the diabetes' hepatic tissue. The therapy with Zn remakes their activities and increases glutathione synthesis. The Zn protecting effect in lipidic peroxidating process also acts upon hepatocyte membrane, fact illustrated by the decrease of LDH in the plasma of the animals treated with Zn.