19 0 0 0 OA ノイロトロピンによるセロトニン下行性疼痛抑制系の賦活化と鎮痛作用
- 著者
- 岡井 恒 古江 秀昌 吉村 恵
- 出版者
- 日本疼痛学会
- 雑誌
- PAIN RESEARCH (ISSN:09158588)
- 巻号頁・発行日
- vol.23, no.1, pp.11-18, 2008-02-20 (Released:2013-07-04)
- 参考文献数
- 16
- 被引用文献数
- 6 4
Neurotropin®, a non protein extract from inflamed rabbit skin inoculated with vaccinia virus, is well known as an analgesic for chronic pain such as low back pain and postherpetic neuralgia, etc. In previous behavioral studies, we have shown that neurotropin activates the monoaminergic descending pain inhibitory system. In the present study, we examined the effects of neurotropin on serotonergic neurons in the nucleus raphe magnus (NRM, the origin of serotonergic descending pain inhibitory neuron) in the rostroventromedial medulla using whole-cell patch-clamp technique in brainstem slices. In some instances, recorded neurons were identified as NRM neurons with neurobiotin filled in the recording pipettes. NRM neurons had a resting membrane potential of about -60 mV. Bath application of neurotropin (1.0 NU/mL) depolarized NRM neurons, and it resulted in initiating an action potential under current-clamp conditions. Under voltage-clamp conditions at a holding potential of -70 mV, NRM neurons exhibited spontaneous excitatory postsynaptic currents (EPSCs). Neurotropin (0.2 - 1.0 NU/mL) did not change the frequency and amplitude of spontaneous EPSCs. However, neurotropin dose-dependently induced an inward current in approximately 60% of NRM neurons tested. The neurotropin-induced inward current was observed even in the presence of tetrodotoxin (1 µM). The reversal potential for the current was close to 0 mV, indicating that the neurotropin-induced current is mediated by the activation of non-selective cation channels. Neurotropin produced an inward current, in all neurons immunohistochemically stained for tryptophan hydroxylase (TPH), a marker for serotonergic neuron. These results indicate that neurotropin directly excites serotonergic NRM neurons without affecting the excitatory synaptic inputs to NRM neurons. This facilitatory action of neurotropin on serotonergic NRM neurons may have an important role for the neurotropin-induced analgesia.
1 0 0 0 OA 疼痛性サイトカインが及ぼす中枢性内臓機能異常の解明-in vivoパッチ解析-
本研究は、慢性疼痛の一つである神経障害性疼痛の発現時にみられる炎症性サイトカインが内臓、特に下部尿路の自律神経制御に与える影響について調べることを目的として行われた。炎症性サイトカインを脊髄に灌流投与を行ったところ、頻尿を誘発するサイトカインと、排尿間隔を広げるものがあることがわかった。また、下部尿路から脊髄への伝達では膀胱と尿道のそれぞれから別々の神経を介して情報が伝達されることがわかった。これらの結果から、下部尿路から脊髄へ入力された圧変化や知覚の情報は複数の種類の細胞に伝達され、これらの細胞にサイトカインが作用し、排尿に影響を与えることがこれまでの研究によって示唆された。