Abstract：
This is a nonclinical, controlled, and triple-blind study to investigate the effects of codeine-associated geraniol on the modulation of orofacial nociception and its potential central nervous system depressing effect in an animal model. The orofacial antinociceptive activity of geraniol in combination with codeine was assessed through the following tests: (i) formalin-induced pain, (ii) glutamate-induced pain, and (iii) capsaicin-induced pain. Six animals were equally distributed into six groups and received the following treatments, given intraperitoneally (i.p.) 30 minutes before the experiments: a) geraniol/codeine 50/30 mg/kg; b) geraniol/codeine 50/15 mg/kg; c) geraniol/codeine 50/7.5 mg/kg; d) geraniol 50 mg/kg; e) codeine 30 mg/kg (positive control); or f) 0.9% sodium chloride (negative control). We performed pain behavior analysis after the injection of formalin (20 µL, 20%), glutamate (20 µL, 25 µM), and capsaicin (20 µL, 2.5 µg) into the paranasal region. Rubbing time of the paranasal region by the hind or front paw was used as a parameter. In the neurogenic phase of the formalin test, the geraniol/codeine at 50/7.5 mg/kg was able to promote the maximum antinociceptive effect, reducing nociception by 71.9% (p < 0.0001). In the inflammatory phase of the formalin test, geraniol/codeine at 50/30 mg/kg significantly reduced orofacial nociception (p < 0.005). In the glutamate test, geraniol/codeine at 50/30 mg/kg reduced the rubbing time by 54.2% and reduced nociception in the capsaicin test by 66.7% (p < 0.005). Geraniol alone or in combination does not promote nonspecific depressing effects on the central nervous system. Based on our findings, we suggest the possible synergy between geraniol and codeine in the modulation of orofacial pain.
摘要：
这是非临床的，控制,和三盲研究，以研究可待因相关香叶醇对口面部伤害感受的调节及其潜在的中枢神经系统抑制作用。通过以下测试评估了香叶醇与可待因组合的口腔镇痛活性：（i）福尔马林引起的疼痛，（ii）谷氨酸引起的疼痛，和(iii)辣椒素诱导的疼痛。将六只动物平均分为六组，并接受以下治疗：实验前30分钟腹膜内（i.p.）给予：a）香叶醇/可待因50/30mg/kg；b）香叶醇/可待因50/15mg/kg；c）香叶醇/可待因50/7.5mg/kg；d）香叶醇50mg/kg；e）可待因30mg/kg（阳性对照）；或f）0.9％氯化钠（阴性对照）。我们在注射福尔马林(20微升，20%),谷氨酸(20微升,25µM)，和辣椒素（20微升，2.5µg）进入鼻旁区。使用后爪或前爪对鼻旁区的摩擦时间作为参数。在福尔马林测试的神经发生阶段，50/7.5mg/kg的香叶醇/可待因能够促进最大的镇痛作用，减少71.9%的伤害感受（p<0.0001）。在福尔马林试验的炎症阶段，香叶醇/可待因在50/30mg/kg时显著降低口面部伤害感受(p<0.005)。在谷氨酸测试中，香叶醇/可待因在50/30mg/kg时，摩擦时间减少了54.2％，辣椒素试验中的伤害感受减少了66.7％（p<0.005）。单独或组合使用香叶醇不会促进对中枢神经系统的非特异性抑制作用。根据我们的发现,我们建议香叶醇和可待因在调节口面部疼痛中可能存在协同作用。
