Mechanism of analgesic action of some phenolic compounds used for dental practice.

用于牙科实践的一些酚类化合物的镇痛作用机制。

• 批准号: 03670885
• 负责人: TAKAHASHI Hiroshi
• 金额: $ 1.28万
• 依托单位: Fukuoka Dental College
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for General Scientific Research (C)
• 财政年份: 1991
• 资助国家: 日本
• 起止时间: 1991 至 1992
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-03670885/
• 关键词: Phenolic compounds; Eugenol; Guaiacol; Substance P release; Capsaicin; Nuerogenic inflammation; ユージノール; フェノ-ル性歯髄鎮痛薬; 歯髄とサブスタンスP; ユ-ジノ-ル鎮痛; グアヤコ-ル鎮痛; カプサイシン鎮痛; 歯髄炎

Neurogenic inflammation, which involves the release of neuropeptides from capsaicin-sensitive sensory nerves, may contribute to inflammatory diseases in tissues such as skin, airways and gut. We had confirmed the existense of substance P (SP)- containing fibers in rat dental pulp, and have suggested that pulpitis may also be neurogenic inflammatory diseases. Capsaicin has been known as a releaser and depletor of SP, and phenolic compounds partly resemble capsaicin in chemical structure. Thus, the present study investigated the effects of eugenol (EG), guaiacol (GC) and thymol (TM) on analgesic action, blood flow and SP release in comparison with capsaicin, and the results were as follows : 1) Pain sensitivity was measured in three ways (heat, pressure and chemical stimuli), and the order of potency for analgesia was EG>HC>TM when these were administered intrathecally in mice, but was weaker than that of capsaicin. 2) EG increased cutaneous blood flow which was measured with a laser Doppler devise in rat hindpaw, and this was antagonized by spantide (an SP antagonist), in the same manner as capsaicin. 3) Rat mandibular incisor pulps were desected out and chopped, and slices weighing about 110 mg were transfered to superfusion chamber. SP release from slices of pulp was increased by EG and GC, but was less than by capsaicin. SP release from slices of rat spinal cord by EG and GC was equal to the potency of capsaicin.These results suggest that phenol analogues such as EG and GC may have a neurotoxic action which releases and depletes SP from small diameter sensory fibers like capsaicin, and may cause analgesic and anti-inflammatory effect. Furthermore, it is possible that capsaicin will be able to use as analgesics for dental practice.

神经源性炎症涉及从辣椒素敏感的感觉神经释放神经肽，可能导致皮肤，气道和肠道等组织中的炎症性疾病。我们已经证实了P（SP）的存在 - 大鼠牙髓中含有纤维，并建议牙髓炎也可能是神经源性炎性疾病。辣椒素被称为SP的释放剂和消耗，酚类化合物在化学结构中部分类似于辣椒素。因此，本研究研究了与辣椒素相比，研究丁香酚（EG），藻醇（GC）和百里醇（TM）对镇痛作用，血流和SP释放的影响，结果如下：1）疼痛敏感性以三种方式测量了三种方式（热，压力和化学刺激的序列），以及在校准中施加了校准的均值。小鼠，但比辣椒素弱。 2）例如，用激光多普勒在大鼠后爪中测量的皮肤血流增加，这与辣椒蛋白相同的方式被Spantide（SP拮抗剂）拮抗。 3）应该将大鼠下颌切牙纸浆切碎并切碎，并将重约110毫克的切片转移到超级灌注室中。 EG和GC增加了纸浆切片的SP释放，但小于辣椒素。 EG和GC从大鼠脊髓切片中释放SP等于辣椒素的效力。这些结果表明，例如EG和GC等苯酚类似物可能具有神经毒性作用，可以释放出从小型直径纤维中释放出的SP，例如辣椒蛋白，并且可能引起镇痛和抗抑制性效应。此外，辣椒素可能能够用作牙科实践的镇痛药。

项目成果

G.Kozam: "The effect of eugenol on nerve transmission." Oral Surg.44. 799 (1977)

G.Kozam：“丁子香酚对神经传递的影响。”

A.G.Hays et al.: "The effects of a series of capsaicin analoges on nociception and body temperature in the rat." Life Sci.34. 1241 (1984)

A.G.Hays 等人：“一系列辣椒素类似物对大鼠伤害感受和体温的影响。”

H.Trowbride et al.: "Effect of zinc oxide-eugenol and hydroxide on intradental nerve activity." J.Endodontics. 8. 403 (1982)

H.Trowbride 等人：“氧化锌-丁子香酚和氢氧化物对牙内神经活动的影响。”

高橋宏,柴田学,大久保つや子: "ユ-ジノール、グアヤコールのアブスタンスPを中心にした消炎鎮痛作用機序" 歯科基礎医学会雑誌. (投稿準備中).

Hiroshi Takahashi、Manabu Shibata、Yako Oku：“以 Abstance P 为中心的丁子香酚和愈创木酚的抗炎和镇痛作用机制”日本基础牙科医学会杂志（准备提交）。