脊髄アデノシン A_1 受容体活性化によるアロディニアの調節
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概要
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Spinally delivered adenosine receptor agonists and its analogs have recently been shown to have antinociceptive effects. However, the mechanisms by which adenosine produces antinociception are not clear. Therefore, the present study evaluated the modulating effect of adenosine A_1 receptor agonist, R-PIA injected intrathecally (I. T.) on the tactile-allodynia, associated with cerebrospinal fluid (CSF)-glutamate release induced by injection of gammna amino butyric acid. The microdialysis probe and polyethylene tube (PE-10) was intrathecally implanted into lumbar segment under halothane anesthesia in fourty-three Sprague-Dawley rats. After three days, rats were divided into three groups ; i) Control (saline, I. T.) ; ii) R-PIA at doses of 1nM, 3nM, and 10nM, and iii) 10nM R-PIA plus 300nM aminophylline. The tactile-allodynia was evaluated by touch-evoked agitation (TEA) which was scored 0 (no response to hair touching at lumbar level) to 3 (strong agitation appeared). Using an intrathecal microdialysis, glutamate concentration in cerebrospinal fluid (CSF-Glu) was periodically (10min intervals) determined simultaneously by a HPLC-ECD. Intrathecal BIC injection evoked a transient strong agitation (TEA score : 4.7 at 10min, 1.0 at 30min), associated with increased CSF-glu (70% at 10min.). R-PIA attenuated such increases of TEA and CSF-glu dose-dependently (3nM : 1.2 and 0.3, 10nM : 0.3 and 0.1). Such action of R-PIA (10nM) was reversed by codeliverly of aminophylline (300nM). Based on the present study, it is clearly demonstrated that R-PIA can prevents allodynia in a dose-dependent manner. This attenuating effect was reversed by adenosine A_1 receptor antagonist, suggesting R-PIA has a potent anti-allodynic effect via inhibiting adenosine A_1 receptor activity at spinal cord. In addition, the microdialysis study demonstrated that R-PIA attenuates increased spinal glutamate release evoked by allodynia through presynaptic inhibition of primary afferent input.
- 九州歯科学会の論文
- 2000-02-25
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