Conclusions The present study established EPZ-5676 price a novel animal model of inflammatory tongue pain in rats, and explored potential roles of the mGluR5 ERK signaling in the development of mechanical and heat hypersensitivity that evolved in the inflamed tongue. Further elucidation of the mechan isms underlying this model of pathological tongue pain may shed new light on the pathogenesis and therapeutic strategies of some clinically relevant, tongue associated diseases such as burning mouth syndrome. Inhibitors,Modulators,Libraries Background Glutamate is the major excitatory neurotransmitter in the mammalian central nervous system. At high extracellular levels, this excitatory amino acid is an ex tremely potent neurotoxin. Extracellular glutamate con centrations in the CNS are regulated by a family of high affinity, Na dependent glutamate transporters.
Five subtypes Inhibitors,Modulators,Libraries of transporters, EAAT1 EAAT5, have been identi fied, two of which, the glutamate transporter GLT 1 and glutamate aspartate transporter GLAST, are predominantly Inhibitors,Modulators,Libraries present on astrocytes and are the major glutamate transporters in the CNS. Mal function or aberrant expression of these glutamate transporters can cause accumulation of toxic concen trations of glutamate and trigger neurodegeneration. Reduced GLT 1 protein expression occurs in brain injury or ischemia, Alzheimers disease, Huntingtons disease, HIV 1 associated dementia, and experimental autoimmune encephalomyelitis. In EAE, for example, GLT 1 and GLAST proteins are down regulated in the spinal cord at the peak of disease symp toms, with no recovery in expression after remission.
These data emphasize Inhibitors,Modulators,Libraries the importance of the astrocyte GLT 1 transporter for normal brain function and its con tribution to multiple CNS pathologies. Astrocytes are often associated with Inhibitors,Modulators,Libraries the pathogenesis of infectious and immune inflammatory responses in volving the CNS and are a major source of chemokines, such as monocyte chemoattractant protein 1, macrophage inflammatory protein 1, inflam matory protein 10, RANTES and MIP 2. Proinflammatory mediators such as lipopolysaccharide, tumor necrosis factor, and IL 1 induce astrocytes to release many of these chemokines in vitro. Chemokines and their receptors are involved in neurological diseases, including multiple sclerosis, Alz heimers disease, HAD, and cerebral ischemia. However, the role of chemokines in the expression of glial glutamate transporters is unclear.
A novel CXC chemokine, MIP 2�� was identified and characterized from a human dendritic cell cDNA library. MIP 2�� mRNA is widely and constitutively expressed in normal tissues, in cluding the brain. MIP 2�� exhibited potent chemotaxis on neutrophils, best was less active on DCs, and inactive on monocytes, NK cells, and T and B lymphocytes. We found that MIP 2�� mRNA expression within the CNS of EAE mice varied at the onset, peak, remission, and re lapse.