Establishment of trigeminal neuralgia model and role of ATP receptor for neuropathic pain

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ATP receptors play an important role of establishment of neuropathic pain. Moreove, it has been found that a major inhibitory neurotransmitter, γ-aminobutyric acid (GABA) functions as an excitatory neurotransmitter through ATP receptor activation. Intracellular Cl^- concentration of normal neurons is less than 10 mM, and external Cl concentration in the brain is around 120-130mM. Under these conditions, GABA causes inward flux of Cl^- through GABA typeA channels. In contrast, when intracellular Cl^- concentration increases during development stage of neuros and peripheral nerve injury, GABA cause outward flux of Cl^-. Consequently, GABA relase resulted in neuronal excitation. This change of GABA function is also found in neuropathic pain model. Thus, functions of cloride transporters were investigated, using electorphysilogical approach and yeast two-hybrid system in this period.The yeast two-hybrid system revealed that neuron-specific K^+-Cl^- cotransporter, KCC2, interacted with brain-type creatine kinase. In addition, using HEK293 cells stablly expressed KCC2, brain-type creatine kinase activated KCC2,resulting in an increase of intracellular Cl^-.