Phantom pain

Almost anyone with a limb amputation experiences phantom sensations. Moreover, the majority of amputees experience pain. This phenomenon is known as ‘Phantom pain’ and is described as the pain felt from a body part, usually a limb, which is no longer present. Several mechanisms have been proposed in attempt to explain this phenomenon with some being more prevalent than others. Cortical remapping seems to explain a substantial part of the occurrence of phantom pain and will be focused upon throughout this review. Since the exact mechanism underlying phantom limb pain is unknown, treatment for this condition is still quite primitive and is mostly by trial and error. However, ‘Mirror Therapy’ has recently been suggested which seems to show promising results for the effective treatment of phantom pain.peer-reviewe

The spectrum of Ischemia-induced white matter injury varies with age

Stroke is a neurological condition that targets the whole range of the human population, from the pre-term infant to the elderly and is a major cause of death worldwide (Ingall 2004). During its lifespan, the brain's vulnerability to hypoxia-ischemia varies. Term infants who suffer this insult usually exhibit widespread neuronal injury in the cerebral cortex with a stroke-like distribution of damage (Deng 2008), whereas in pre-term infants immature oligodendrocytes and subplate neurons below the neocortex are most vulnerable and result in Periventricular Leukomalacia (PVL) (Back et al. 2007; McQuillen et al. 2005). The incidence of stroke decreases in young adulthood, but peaks again in the elderly. Moreover, the underlying pathological mechanisms that occur following ischemia are different at each stage. Experimental stroke research on stroke has traditionally focused on grey matter injury, but recent evidence indicates that white matter injury is a critical part of its pathophysiology. In this debilitating condition the mechanisms of ischemia-induced damage differ with age and all cellular components of white matter (axons, oligodendrocytes and astrocytes) are affected. This review paper focuses on the relative vulnerability to ischemia of white matter during the course of development and on our recent findings of how individual cellular components are affected during each stage.peer-reviewe

Behavioural microanalysis of dopamine autoreceptor function

Low doses of dopamine autoreceptor (DA) agonists are presumed to act by stimulating DA autoreceptors on the sona/dendrites and axon terminals of DA neurons. Low doses of apomorphine reduced food Intake, in a microstructural analysis paradigm, by reducing both the time spent feeding and the rate of food ingestion. The reduction of eating time was shown to result from the stimulation of DA autoreceptors located on the cell bodies and dendrites of the mesolimbic DA system. The reduction of eating rate however, appeared to result from the activation of axon terminal DA autoreceptors. The significance of this dissociation is discussed in relation to the mechanisms through which presynaptic DA receptors on the same neuron may subserve different behavioural functions. The observation that apomorphine administration resulted in a selective manipulation of the microstructural parameters of feeding, was then used to assess the action of antidepressant drugs on DA autoreceptor function. In both normal and chronically stressed rats, chronic antidepressant treatment failed to alter the sensitivity of DA autoreceptors. However, on withdrawal, the sensitivity of cell body DA autoreceptors appeared reduced, as apomorphine no longer in any way influenced the time spent feeding in the microstructural paradigm. The Implications of these findings are discussed in relation to the hypothesis that antidepressant drugs increase DA function by reducing the sensitivity of presynaptic DA receptors

Prevalance study of glaucoma in Malta and Gozo

A glaucoma survey was carried out in Malta and Gozo. Using non-contact pulseair tonometer, 2245 participants selected on a random basis, aged 40 years and above, were examined and 3.29% were found to have glaucoma. Among them 1.69% were newly detected glaucoma cases. The main risk factors were diabetes mellitus in the personal past history and glaucoma in the family history. Age was confirmed to be a risk factor, but arterial hypertension and myopia could not be proved as risk factors. About 4000 glaucoma cases were estimated to be present in Malta and Gozo at the time of the survey. Some other ocular conditions were also found in relatively high percentages: cataract -3.3%, myopic maculopathy -2.9% and diabetic retinopathy -1.5%.peer-reviewe

Two-photon microscopy : sequential imaging studies in vivo

Microscopists have always desired to look inside various organ tissues to study structure, function and dysfunction of their cellular constituents. In the past, this has frequently required tissue extraction and histological preparation to gain access. Traditional optical microscopy techniques, which use linear (one-photon) absorption processes for contrast generation, are limited to use near the tissue surface (< 80 µm) because at greater depths strong and multiple light scattering blurs the images. Scattering particularly strongly affects signal strength in confocal microscopy, which achieves three-dimensional resolution and optical sectioning with a detection pinhole that rejects all light that appears not to originate from the focus. New optical microscopy techniques have been developed that use nonlinear light-matter interactions to generate signal contrast only within a thin raster-scanned plane. Since its first demonstration over a decade ago, two-photon microscopy has been applied to a variety of imaging tasks and has now become the technique of choice for fluorescence microscopy in thick tissue preparations and in live animals. The gain in resolution over conventional in vivo imaging techniques has been several orders of magnitude. Neuroscientists have used it to measure calcium dynamics deep in brain slices and in live animals, blood flow measurement, neuronal plasticity and to monitor neurodegenerative disease models in brain slices and in live rodents. These types of applications define the most important niche for two-photon microscopy - high-resolution imaging of physiology, morphology and cell-cell interactions in intact tissue. Clearly the biggest advantage of two-photon microscopy is in longitudinal monitoring of rodent models of disease or plasticity over days to weeks. The aim of this article is to discuss some methodological principles, and show some applications of this technique obtained from our laboratory in the area of acute experimental stroke research.peer-reviewe

Vulnerability of white matter to ischemia varies during development

Stroke is the one of the leading causes of mortality and morbidity in developed countries. The central role of injury to white matter in the pathophysiology of stroke has been recognised over the recent years. Stroke can affect a wide range of the population (from the premature infant to the elderly) and therefore the mechanism of injury of central white matter may vary with age. The main aim of this review paper is to shed some light on the difference in maturation of injury to the axon-oligodendrocyte unit following an ischemic insult between different developmental stages. Both components of this unit exhibit varying degrees of susceptibility to ischemia throughout their development. Axons are particularly resistant to ischemia in the neonatal stage. However, they show a marked decreased in tolerance to ischemia during the period of myelination. Late oligodendrocyte progenitor cells (OPC) are the most sensitive type of oligodendrocyte, and their role in periventricular leukomalacia (PVL) is well known. On the other hand, early OPC are particularly resistant to ischemia. Studying the effect of ischemia on white matter in the brain during the different developmental stages will lead to a better understanding of the pathophysiology of white matter injury and hopefully, in the future, to the development of new therapeutic strategies of the various white matter diseases.peer-reviewe

Lateral Habenula contribution in Nicotine addiction : focus on Dopamine, GABA and Serotonin Interactions

Compelling evidence has shown a pivotal role of dopaminergic function in drug addiction. Recently, the Habenula (Hb) has attracted a great deal of attention as another target for nicotine in the brain because of its role in regulating dopamine (DA), gamma-aminobutyric acid (GABA) and serotonin (5-HT) systems. Nicotine acts binding to acetylcholine receptors that are widely distributed in the brain. Interestingly, the receptor subtypes that mediate nicotine withdrawal responses are highly expressed in the Hb. Moreover, the block of habenular nicotinic receptors in animals chronically treated with nicotine enhances withdrawal responses once nicotine is discontinued. Furthermore, it has been shown how a high dose of nicotine can cause massive degeneration almost exclusively in the medial habenula (MHb) and its output tract, the fasciculus retroflexus. Thus, symptoms associated with nicotine withdrawal may be caused by dysfunctions of the Hb output. Therefore, Hb might be of fundamental importance in the expression of nicotine reinforcing properties and withdrawal. Here, we will focus on the role of the lateral habenula (LHb) on nicotine modulation of DA function and we will evaluate LHb interaction with the rostromedial tegmental nucleus (RMTg), a GABAergic area, and the serotonergic raphé nuclei. Furthermore, as LHb has high density expression of 5-HT2C receptors, these subtypes might be important in the control of its neuronal activity and output to the midbrain monoaminergic and GABAergic systems.peer-reviewe

Prospective three-year follow up of a cohort study of 240 patients with chronic facial pain

Background: Patients often present with facial pain ascribed to sinusitis, despite normal nasal endoscopy and sinus computed tomography. Facial pain is increasingly recognised to be of neurological origin. Method: A cohort of 240 patients with chronic facial pain was followed up for 36 months at an otolaryngological practice in Malta. The types of facial pain were classified according to International Headache Classification criteria. The body mass index, occupation and educational level of patients were compared with the general population. Results: Tension-type mid-facial pain and facial migraine without aura were the most common types of chronic facial pain. The sites of pain, symptoms, treatment and outcomes for these principal pain types are discussed. Patients with mid-facial pain were treated with low-dose amitriptyline for eight weeks. After three years, nearly half of the patients were symptom free, and in a third the pain changed from being chronic to being episodic. The treatment of patients with facial migraine was more varied but the length of time until recurrence of pain was similar. Conclusion: The most effective long-term treatments for tension-type mid-facial pain and facial migraine were low-dose amitriptyline and low-dose amitriptyline and triptans, respectively.peer-reviewe

The central role of aquaporins in the pathophysiology of ischemic stroke

Stroke is a complex and devastating neurological condition with limited treatment options. Brain edema is a serious complication of stroke. Early edema formation can significantly contribute to infarct formation and thus represents a promising target. Aquaporin (AQP) water channels contribute to water homeostasis by regulating water transport and are implicated in several disease pathways. At least 7 AQP subtypes have been identified in the rodent brain and the use of transgenic mice has greatly aided our understanding of their functions. AQP4, the most abundant channel in the brain, is up-regulated around the peri-infarct border in transient cerebral ischemia and AQP4 knockout mice demonstrate significantly reduced cerebral edema and improved neurological outcome. In models of vasogenic edema, brain swelling is more pronounced in AQP4-null mice than wild-type providing strong evidence of the dual role of AQP4 in the formation and resolution of both vasogenic and cytotoxic edema. AQP4 is co-localized with inwardly rectifying K+-channels (Kir4.1) and glial K+ uptake is attenuated in AQP4 knockout mice compared to wild-type, indicating some form of functional interaction. AQP4-null mice also exhibit a reduction in calcium signaling, suggesting that this channel may also be involved in triggering pathological downstream signaling events. Associations with the gap junction protein Cx43 possibly recapitulate its role in edema dissipation within the astroglial syncytium. Other roles ascribed to AQP4 include facilitation of astrocyte migration, glial scar formation, modulation of inflammation and signaling functions. Treatment of ischemic cerebral edema is based on the various mechanisms in which fluid content in different brain compartments can be modified. The identification of modulators and inhibitors of AQP4 offer new therapeutic avenues in the hope of reducing the extent of morbidity and mortality in stroke.peer-reviewe