Role of the trigeminal mesencephalic nucleus in rat whisker pad proprioception.

BACKGROUND: Trigeminal proprioception related to rodent macrovibrissae movements is believed to involve skin receptors on the whisker pad because pad muscles operate without muscle spindles. This study was aimed to investigate in rats whether the trigeminal mesencephalic nucleus (TMnu), which provides proprioceptive feedback for chewing muscles, may be also involved in whisker pad proprioception. METHODS: Two retrograde tracers, Dil and True Blue Chloride, were injected into the mystacial pad and the masseter muscle on the same side of deeply anesthetized rats to label the respective projecting sensory neurons. This double-labeling technique was used to assess the co-innervation of both structures by the trigeminal mesencephalic nucleus (TMnu).In a separate group of anesthetized animals, the spontaneous electrical activities of TMnu neurons were analyzed by extracellular recordings during spontaneous movements of the macrovibrissae. Mesencephalic neurons (TMne) were previously identified by their responses to masseter muscle stretching. Changes in TMne spontaneous electrical activities, analyzed under baseline conditions and during whisking movements, were statistically evaluated using Student's t-test for paired observations. RESULTS: Neuroanatomical experiments revealed different subpopulations of trigeminal mesencephalic neurons: i) those innervating the neuromuscular spindles of the masseter muscle, ii) those innervating the mystacial pad, and iii) those innervating both structures. Extracellular recordings made during spontaneous movements of the macrovibrisae showed that whisking neurons similar to those observed in the trigeminal ganglion were located in the TMnu. These neurons had different patterns of activation, which were dependent on the type of spontaneous macrovibrissae movement. In particular, their spiking activity tonically increased during fan-like movements of the vibrissae and showed phasic bursting during rhythmic whisking. Furthermore, the same neurons may also respond to masseter muscle stretch. CONCLUSIONS: results strongly support the hypothesis that the TMnu also contains first-order neurons specialized for relaying spatial information related to whisker movement and location to trigeminal-cortical pathways. In fact, the TMnu projects to second-order trigeminal neurons, thus allowing the rat brain to deduce higher-order information regarding executed movements of the vibrissae by combining touch information carried by trigeminal ganglion neurons with proprioceptive information carried by mesencephalic neurons.

Olfactory and gustatory function impairment in COVID-19 patients: Italian objective multicenter-study.

BACKGROUND: Objective data on chemosensitive disorders during COVID-19 are lacking in the Literature. METHODS: Multicenter cohort study that involved four Italian hospitals. Three hundred and forty-five COVID-19 patients underwent objective chemosensitive evaluation. RESULTS: Chemosensitive disorders self-reported by 256 patients (74.2%) but the 30.1% of the 89 patients who did not report dysfunctions proved objectively hyposmic. Twenty-five percentage of patients were seen serious long-lasting complaints. All asymptomatic patients had a slight lowering of the olfactory threshold. No significant correlations were found between the presence and severity of chemosensitive disorders and the severity of the clinical course. On the contrary, there is a significant correlation between the duration of the olfactory and gustatory symptoms and the development of severe COVID-19. CONCLUSIONS: Patients under-report the frequency of chemosensitive disorders. Contrary to recent reports, such objective testing refutes the proposal that the presence of olfactory and gustatory dysfunction may predict a milder course, but instead suggests that those with more severe disease neglect such symptoms in the setting of severe respiratory disease.

The muscle relaxant thiocolchicoside is an antagonist of GABAA receptor function in the central nervous system.

Thiocolchicoside (TCC) is used clinically for its muscle relaxant, anti-inflammatory, and analgesic properties, and it has been shown to interact with gamma-aminobutyric acid (GABA) type A receptors (GABAARs) and strychnine-sensitive glycine receptors in the rat central nervous system. In contrast to a proposed agonistic action at these two types of inhibitory receptors, pharmacological evidence has shown that, under certain conditions, TCC manifests convulsant activity in animals and humans. We now show that the phasic and tonic GABAAR-mediated currents recorded from Purkinje cells and granule neurons, respectively, in parasagittal cerebellar slices from adult male rats were inhibited by TCC in a concentration-dependent manner. The median inhibitory concentrations of TCC for these effects were approximately 0.15 and approximately 0.9 microM, respectively. TCC did not potentiate GABABR-mediated currents in hippocampal slices, suggesting that its muscle relaxant action is not mediated by GABABRs. Intraperitoneal injection of TCC in rats either alone or in combination with negative modulators of GABAergic transmission revealed convulsant and proconvulsant actions of this drug. Our data, consistent with clinical observations of the epileptogenic effect of this compound, suggest that TCC is a potent competitive antagonist of GABAAR function.

Focal and secondarily generalised convulsive status epilepticus induced by thiocolchicoside in the rat.

The objective of this study was to document the convulsant properties of thiocolchicoside in rats, and to characterise the electroclinical pattern of epileptic seizures. Experiments were carried out in three groups of male Wistar rats: in group A, thiocolchicoside was applied topically to the pia, or given by microinjection to the cerebral cortex (2 microg/microl); in group B, the drug was administered parenterally (6 mg/kg) to rats with minimal lesions of the dura and arachnoid membranes; in group C, thiocolchicoside was administered parenterally (up to 12 mg/kg) to intact rats. In all animals, electroclinical activity was continuously monitored for at least 3 hours after thiocolchicoside injection or application. In group A, electrographic and behavioural activity of focal motor seizures occurred in 100% of animals, developing into a focal status epilepticus; in group B, a multifocal epileptic pattern with secondary generalisation, clinically characterised by clonic or tonic-clonic seizures occurred in 100% of animals, until a secondarily generalised convulsive status epilepticus; in group C, none of animals showed either electrographic or behavioural seizure activity. Our study documents that thiocolchicoside has a powerful convulsant activity in the rat, perhaps due to an antagonistic interaction of the compound with a cortical subtype of the GABA(A) receptor.