@article{oai:dmu.repo.nii.ac.jp:00001295,
 author = {小林, 俊策 and Kobayashi, Shunsaku},
 issue = {1},
 journal = {Dokkyo journal of medical sciences},
 month = {Mar},
 note = {悪性骨腫瘍あるいはがんの骨転移の患者の多くが重篤な痛みに苦しんでいる.X線照射は,これらの疼痛を和らげるためにしばしば用いられている.腫瘍による骨性痛の発症機序は多様であり,その一部は神経障害性疼痛の要因によると考えられる.神経障害性疼痛の発症機序の一つとして,脊髄後角表層ニューロンの細胞膜内外のクロライド濃度勾配の障害がある.今回の研究では,腫瘍による骨性痛の発症にクロライド濃度勾配の障害が関与しているかを検討した.実験には,NCTC2472がん細胞をC3H/HeNマウスの大腿骨に接種する骨転移モデルマウスを用いた.また,20グレイのX線照射による除痛効果についても検討した.腫瘍による骨性痛は,KCC2の発現減少,Iba1およびGFAPの発現増加を伴っていた.これらの事は,クロライド電流の逆転電位の脱分極側へのシフトを示唆する.大腿骨局部へのX線照射後4日目には,腫瘍による骨性痛の緩和が見られ,KCC2,Iba1およびGFAPの発現レベルが正常値へ戻った.クロライドの恒常性障害が,脊髄後角における興奮性シナプス伝達の脱抑制を起こし腫瘍による骨性痛を惹起する.また,X線照射による除痛の一部はクロライドの恒常性の正常化によると推測される., Many patients with bone cancer experience severe bone pain. Radiation is one of the most commonly used treatments to relieve this pain. Bone cancer pain is thought to occur through multiple mechanisms including a neuropathic component. One of possible mechanisms for neuropathic pain is disturbance of the transmembrane chloride gradient of spinal superficial dorsal horn(SDH)neurons. In the present study, we investigated whether this hypothesis is valid in bone cancer pain. Experiments were performed in a bone cancer pain model, where NCTC 2472 cancer cells were inoculated into the femur of C3H/HeN mice. We analyzed allodynia induced by bone cancer and pain relief following a single fraction of 20-Gy radiation. Bone cancer pain was associated with a depolarizing shift of the reversal potential of GABAA receptor-mediated currents in the SDH. These changes were accompanied with the downregulation of the potassium chloride cotransporter KCC2 and the up-regulation of microglia marker Iba1 and Glial Gibrillary Acidic Protein(GFAP). Focal irradiation of the affected femur attenuated bone pain as early as 4 days after irradiation. Along with pain relief, the GABAA reversal potential and the expression levels of KCC2, Ib1a, and GFAP were restored near to their control levels. The present findings suggest that disturbance of chloride homeostasis, which leads to dis-inhibition of excitatory synaptic transmission in the SDH, may explain bone cancer pain, and that rapid pain relief achieved by local irradiation may be attributed to a restoration of disturbed chloride homeostasis and synaptic inhibition in the SDH., 原著},
 pages = {59--66},
 title = {骨転移モデルマウスを用いた骨転移痛の発症機序と放射線治療の効果},
 volume = {43},
 year = {2016},
 yomi = {コバヤシ, シユンサク}
}