Cerebral metabolic and vasopressin and oxytocin responses during osmotic stimulation in conscious rats

Intravenous infusion of hypertonic saline increased plasma [Na (+) ] and osmolality and induced a short-latency drinking response. These changes were associated with increased glucose utilization in the supraoptic and paraventricular nuclei and neural lobe, and decreases in the medial septum and nucleus ambiguus. The increases in glucose utilization were more accentuated in the supraoptic nuclei than in paraventricular nuclei, indicating that they are more sensitive to osmotic stimulation than the paraventricular nuclei. In association with enhanced activity in the hypothalamo-neurohypophysial system, plasma vasopressin and oxytocin concentrations increased, with a preferential increase of oxytocin over vasopressin. The hormonal contents in the neural lobe were not depleted by the osmotic stimulus despite the large increases of their concentrations in the plasma.     

Methadone in post-herpetic neuralgia: A pilot proof-of-concept study

OBJECTIVE:

This research was designed as a pilot proof-of-concept study to evaluate the use of low-dose methadone in post-herpetic neuralgia patients who remained refractory after first and second line post-herpetic neuralgia treatments and had indications for adding an opioid agent to their current drug regimens.

METHODS:

This cross-over study was double blind and placebo controlled. Ten opioid naïve post-herpetic neuralgia patients received either methadone (5 mg bid) or placebo for three weeks, followed by a 15-day washout period and a second three-week treatment with either methadone or placebo, accordingly. Clinical evaluations were performed four times (before and after each three-week treatment period). The evaluations included the visual analogue scale, verbal category scale, daily activities scale, McGill pain questionnaire, adverse events profile, and evoked pain assessment. All patients provided written informed consent before being included in the study. ClinicalTrials.gov: {"type":"clinical-trial","attrs":{"text":"NCT01752699","term_id":"NCT01752699"}}NCT01752699

RESULTS:

Methadone, when compared to placebo, did not significantly affect the intensity of spontaneous pain, as measured by the visual analogue scale. The intensity of spontaneous pain was significantly decreased after the methadone treatment compared to placebo on the category verbal scale (50% improved after the methadone treatment, none after the placebo, p = 0.031). Evoked pain was reduced under methadone compared to placebo (50% improved after the methadone treatment, none after the placebo, p = 0.031). Allodynia reduction correlated with sleep improvement (r = 0.67, p = 0.030) during the methadone treatment. The side effects profile was similar between both treatments.

CONCLUSIONS:

Methadone seems to be safe and efficacious in post-herpetic neuralgia. It should be tried as an adjunctive treatment for post-herpetic neuralgia in larger prospective studies.     

Effects of nitric oxide on expressions of nitrosocysteine and calcium-activated potassium channels in the supraoptic nuclei and neural lobe of dehydrated rats

Using a rhythmic isometric force production paradigm, we investigated the after-effects of in-phase and antiphase bimanual performance on the unintended recruitment of the homologous muscles of the opposite limb during subsequent performance of tasks that were unimanual by design. Electromyograms obtained from the muscles of the opposite limb were analyzed in terms of their amplitude and the distribution of their phase relative to that of the intended movements. Preceding bimanual activity had distinct effects on the relative phase (mean and uniformity) of the structured electromyograms. These were particularly pronounced following performance of the in-phase pattern. These findings are discussed in terms of interhemispheric excitation and inhibition.     

Role of prostaglandin,endothelin and sympathetic nervous system on the L-NAME-induced pressor responses in spontaneously hypertensive rats

We tested the hypothesis that in spontaneously hypertensive rat (SHR) NO produced centrally influences the resting arterial blood pressure by attenuating mechanisms involving prostaglandins, angiotensin II, endothelin and sympathetic nervous system. L-NAME (200 micro g/5 micro l), an inhibitor of NO synthase, administered intracerebroventricularly (i.c.v.) to awake and freely moving rats increased mean arterial blood pressure (MABP) in a biphasic pattern: an early transient increase within 1 min and a late prolonged response starting at 45 min and persisting for the duration of experiment (180 min). The two pressor responses involve different neurochemical mechanisms and, based on their latencies, they appear to reflect different anatomical sites of action of L-NAME. The late, but not the early pressor response, was prevented by pretreatment with chlorisondamine (2.5 mg/kg, i.v.), a ganglionic blocker, indicating its dependence on the sympathetic nervous system. Both pressor responses were abolished by i.c.v. pretreatment with indomethacin (200 micro g/5 micro l, i.c.v.), an inhibitor of cyclo-oxygenase, showing that they are mediated by prostaglandin(s). In contrast, losartan (25 micro g/5 micro l), an angiotensin II AT(1) receptor antagonist, had no effect. The initial pressor response was also attenuated by pretreatment with the endothelin ET(A)/ET(B) receptor antagonist, PD 145065 (48 micro g/2 micro l, i.c.v.). Intravenous pretreatment with another ET(A)/ET(B) receptor antagonist, L-754,142 (15 mg/kg as a bolus+15 mg/kg/h for 180 min), however, attenuated both responses to L-NAME. It is possible that L-754,142 crossed the blood-brain barrier and blocked, in addition, central ET(A)/ET(B) receptors. These studies show that NO synthesized in the brain attenuates pressor mechanisms involving prostaglandin, endothelin and sympathetic nervous system, but not angiotensin II, to modulate resting arterial blood pressure.     

Neural systems responsible for the gastric secretion provoked by 2-deoxy-D-glucose cytoglucopoenia.

1. The central structures responsible for the gastrosecretory effect of cytoglucopoenia caused by 2-deoxy-D-glucose (2-DG) were investigated in 105 cats prepared with chronic gastric fistulae and subjected to various experimental procedures. 2. Bilateral electrolytic lesion of the caudalmost two thirds of globus pallidus almost suppressed the secretory response and caused aphagia and adipsia. 3. Secretion in response to 2-DG and feeding behaviour were entirely blocked after making a lesion in a large ventromedial area of the meso diencephalic transition comprising the ventral tegmental area of Tsai, the ventral tegmental decussation, the red nucleus, a ventral portion of the central grey matter, the interstitial nuclei of Darkschewitsch and of Cajal, the pre-rubral fields, the reticular part of substantia nigra, the internal portion of the cerebral peduncle and the ventral part of the mesencephalic reticular formation. 4. Microinjection of 2-DG in the medial forebrain bundle, at the level of the hypothalamus, caused intense gastric secretion, whereas the same procedure was totally ineffective when the caudalmost two thirds of the globus pallidus were stimulated. 5. Increasing doses of 2-DG, systemically injected, restored the secretory response in volume and acid concentration and output after intercollicular transection of the brain stem. After the transection, secretion of pepsin was only slightly increased when large doses of 2-DG were administered, thus suggesting a differential control of water, acid and pepsin secretion in response to cytoglucopoenia. 6. It is concluded that there are at least three reflex systems involved in gastric secretion due to cytoglucopoenia: (a) a reflex consisting of afferent and efferent pathways in the medial forebrain bundle area; (b) a reflex whose afferent side is from the hypothalamus and efferent side is from the globus pallidus; (c) a reflex with the afferent side probably originating in the liver and the efferent side in the lower brain stem. 7. The pathways involved in the first two arcs run along Nauta's limbic mid-brain circuit. The three systems are possibly related to control of secretion and feeding behaviour.     

Local cerebral glucose utilization in Long-Evans and Brattleboro rats during acute dehydration

The quantitative autoradiographic deoxyglucose method was used to study the effects of acute dehydration on local cerebral glucose utilization in Long-Evans and homozygous Brattleboro rats. Water-sated Brattleboro rats had high rates of glucose utilization in the subfornical organ, habenular complex, septal triangular nucleus and pituitary neural lobe. Deprivation of water for 16-18 h enhanced glucose utilization in these structures, more intensely in the Brattleboro rats, and activated others, particularly those connected to the subfornical organ. In Long-Evans rats, water deprivation increased metabolic activity in the subfornical organ, in several structures with which it is connected, and in other brain regions putatively involved in maintaining fluid balance.     

Effects of antidromic stimulation of the ventral root on glucose utilization in the ventral horn of the spinal cord in the rat.

Electrical stimulation of the proximal stump of the transected sciatic nerve increased glucose utilization in the ventral horn of the spinal cord, with the greater increase in Rexed's lamina IX. Antidromic stimulation of the ventral root, however, did not change glucose utilization in the ventral horn. These results suggest that the axon terminals and not the cell bodies are the sites of enhanced metabolic activity during increased electrical activity in these elements.     

Stimulation of protein synthesis and glucose utilization in the hypoglossal nucleus induced by axotomy

The metabolic responses of rat hypoglossal nuclei to unilateral section of the 12th cranial nerve have been studied. Changes in the rates of protein synthesis and glucose utilization in the regenerating nucleus were determined with two quantitative autoradiographic techniques, the L-[1-14C]leucine method and the [14C] deoxyglucose method, respectively. The results show that both of these processes increase in the nucleus ipsilateral to the sectioned nerve and are unaffected in the contralateral nucleus as compared with sham-operated animals. The time courses of these metabolic changes have been compared with that of the return of functional innervation of the tongue. An increase in glucose utilization is first detected 24 hr postaxotomy. It is maximal between 1 and 3 days postaxotomy and constitutes an 84% increase over the rate in the contralateral control nucleus. The increase in protein synthesis is of smaller magnitude than that of glucose utilization. It is maximal at 48 hr after axotomy and constitutes a 25% increase over the rate in the contralateral nucleus. The increases in both of these metabolic processes persist even after functional recovery of the tongue at 21 days postaxotomy. Protein synthesis and glucose utilization return to normal levels between 24 and 35 days postaxotomy. Although the time courses of the changes in protein synthesis and glucose utilization are similar, the magnitude of the increase in glucose utilization is too large to be accounted for by the energy requirements of the relatively small increase in protein synthesis and probably reflects other processes as well, including altered function of the soma-dendritic membrane of regenerating neurons.     

The effect of hyperbaric oxygen on glucose utilization in a freeze-traumatized rat brain

Local cerebral glucose utilization was measured with the autoradiographic 2-deoxyglucose technique in rats injured by a focal parietal cortical freeze lesion then treated with hyperbaric oxygen (HBO). The cold lesion depressed glucose utilization in the contralateral as well as in the ipsilateral hemisphere. The largest decreases were observed in ipsilateral cortical areas. Treatment of lesioned animals with HBO at 2 atm for 90 minutes on each of 4 consecutive days tended to increase the overall cerebral glucose utilization measured 5 days after injury when compared to animals exposed to normobaric air. This improvement reached statistical significance in five of the 21 structures studied: the auditory cortex, medial geniculate body, superior olivary nucleus, and lateral geniculate body ipsilateral to the lesion, and the mammillary body. The data indicate that changes in lesioned rats exposed to HBO are not restricted to the period of time that the animals are in the hyperbaric chamber but are persistent.     

Nitric oxide up-regulates the expression of calcium-dependent potassium channels in the supraoptic nuclei and neural lobe of rats following dehydration

Nitric oxide (NO) is a gas molecule to signal neurotransmission in the hypothalamo-neurohypophysial system during osmotic regulation. We previously reported that osmotic stimulation increased nitric oxide synthase (NOS) activity in the supraoptic nuclei (SON) and neural lobe. The aim of this study is to define the role of NO in the regulation of Ca(2+)-activated K(+) channels (BK channels) expression in the magnocellular system following dehydration. We used Western blot analysis and quantitative immunocytochemistry to conduct the experiment in rats. In the immunoblot study, we found that water deprivation significantly increased the expression of BK channels in the SON and neural lobes. Dehydration also enhanced the profiles of neurons expressing vasopressin and oxytocin significantly. In about 70% of these neurons, BK channels were co-localized in the same neuron, and their expression increased significantly during dehydration. We further examined the effects of intracerebroventricular administration of sodium nitroprusside (a donor of NO) and L-NAME (an inhibitor of NO synthase) on expression of BK channels in the SON. We found that compared to animals treated with the donor of NO, there were significant decreases in the expression of BK proteins in animals receiving L-NAME. These results suggest that NO may enhance the expression of BK channels in the supraoptic nuclei and neural lobe of rats following dehydration.