Multiple sclerosis central nervous system pathology

Neuropathic pain is defined as spontaneous pain and hypersensitivity to pain associated with damage to or pathologic changes in the peripheral nervous system as in painful diabetic peripheral neuropathy (DPN), acquired immunodeficiency syndrome (AIDS), polyneuropathy, post-herpetic neuralgia (PHN) or pain originating in the central nervous system (CNS), that which occurs with spinal cord injury, multiple sclerosis, and stroke. Functional pain, a relatively newer concept, is pain sensitivity due to an abnormal processing or function of the central nervous system in response to normal stimuli. Several conditions considered to have this abnormal sensitivity or hyperresponsiveness include fibromyalgia and irritable bowel syndrome. 

The study of the Central Nervous System (CNS) is the primary clinical indication for the use of extracellular Gd(III) agents. The majority of these pathologies are brain tumors, and three quarters of them are represented by metastases occurring in patients undergoing treatment for systemic cancer (Fig. 1). Other brain diseases, such as multiple sclerosis and cerebral injuries can be also investigated by contrast-enhanced MRI. 

T-cells are involved in various inflammatory pathologies such as asthma, multiple sclerosis, and human idiopathic polymyositis. The modification of these cells may thus be an important mechanism to help avoid the damage caused by these afflictions. In the natural disease course of multiple sclerosis, for example, apoptosis contributes to the elimination of T-cells from the inflamed central nervous system. Using corticoids to induce apoptosis could contribute to the down-regulation of... 

HHV-6 and HHV-7 from the Rh olovirus genus present a high distribution worldwide with infection rates of respectively 70-100% and 75% (7,8]. Primary infection with HHV-6 results in the development of exanthema subitum and can lead to complications such as malaise, febrile seizures and in some rare cases encephalitis [7]. HHV-6 is heavily associated with diseases of the central nervous system in immunocompromised patients such as encephalitis and/or encephalopathy 7], but also with multiple sclerosis. In particular, anti-HHV-6 antibodies and HHV-6 DNA have been detected in MS cerebrospinal fluid and MS plaques, respectively [9]. So far, the link of HHV-7 and diseases other than exanthema subitum during primary infection remains highly speculative 9-11]. Additional studies are required to understand the true contribution of HHV-7 in pathological conditions. 

COX-2 is constitutively present in the brain, mainly in neurons, and has been shown to play a key role in brain-specific inflammatory episodes linked to the progression of Alzheimer s disease (AD). Epidemiological and clinical studies have observed the influence of NSAID on the evolution of AD, with recent studies showing an inverse correlation between the use of NSAID and the risk of developing AD (Bazan et al., 2002). In the central nervous system, prostanoid levels are normally very low, but they can substantially increase in a variety of pathological conditions such as trauma, ischemia, HIV infection and multiple sclerosis. COX-1 and COX-2 are expressed in the spinal cord. It has been suggested that the antihyperalgesic mechanism of COX-2 inhibitors lies with the modulation of constitutive COX-2 present at the spinal level (S vensson and Yaksh, 2002). 

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