Department of Experimental Physiology, Medical University of Lodz, Mazowiecka 6/8, 92-215 Lodz, Poland.
Brain Res. 2011 Mar 25;1382:19-28. doi: 10.1016/j.brainres.2011.01.018. Epub 2011 Jan 15.
Nociceptive stimulation has been considered to affect the expression of genes encoding endogenous neuropeptides and their receptors. The effect of electric stimulation of the tooth pulp and/or periaqueductal gray (PAG) in rats on mRNA levels of the selected neuropeptides and opioid receptors (ORs) was investigated in comparison with control group, without stimulation. The levels of mRNA for the selected neuropeptides: galanin (GAL), vasopressin (AVP), oxytocin (OT), substance P (SP), somatostatin (SOM), vasoactive intestinal peptide (VIP), endomorphin-2 (EM-2), and opioid receptors: MOR, DOR and KOR in mesencephalic, hypothalamic and thalamic tissues were determined by real-time PCR. It was demonstrated that in the control group expression of the tested neuropeptides was at a very low level in the mesencephalon and thalamus, but at the higher level in the hypothalamus. The highest expression of ORs was observed in the mesencephalon. Nociceptive tooth pulp stimulation had the strongest effect in the hypothalamus, elevating mRNA levels of all tested neuropeptides except SOM. Electric stimulation of PAG either did not change or down-regulated mRNA levels of the neuropeptides in the cerebral structures. Simultaneous stimulation of PAG and tooth pulp either did not affect mRNA levels of the investigated neuropeptides or caused their slight decrease versus tooth pulp stimulation. The noxious stimulation of tooth pulp increased also the levels of OR mRNAs, while stimulation of PAG had the opposite effect. The above results demonstrated that tooth pulp stimulation significantly up-regulated the mRNA levels for a number of neuropeptides and all three types of ORs in the rat brain, which would result in more potent antinociception. In contrast, PAG stimulation down-regulated the mRNA levels of several neuropeptides and ORs in the cerebral tissues, which would cause decreased synthesis of ORs. The obtained results represent a new insight into the mechanism of orofacial pain.
伤害性刺激被认为会影响内源性神经肽及其受体基因的表达。本研究旨在比较牙髓和/或中脑导水管周围灰质（periaqueductal gray，PAG）电刺激与对照组（无刺激）对大鼠选定神经肽和阿片受体（opioid receptor，OR）mRNA 水平的影响。通过实时 PCR 测定中脑、下丘脑和丘脑组织中选定神经肽（甘丙肽（galanin，GAL）、血管加压素（vasopressin，AVP）、催产素（oxytocin，OT）、P 物质（substance P，SP）、生长抑素（somatostatin，SOM）、血管活性肠肽（vasoactive intestinal peptide，VIP）、内吗啡肽-2（endomorphin-2，EM-2）和 OR（MOR、DOR 和 KOR）的 mRNA 水平。结果表明，在对照组中，测试神经肽在中脑和丘脑的表达水平非常低，但在下丘脑的表达水平较高。ORs 的最高表达水平出现在中脑。伤害性牙髓刺激在下丘脑引起最强的反应，除 SOM 外，所有测试神经肽的 mRNA 水平均升高。PAG 电刺激要么不改变，要么下调脑结构中神经肽的 mRNA 水平。同时刺激 PAG 和牙髓既不影响所研究神经肽的 mRNA 水平，也不会导致其相对于牙髓刺激略有下降。牙髓的伤害性刺激也增加了 ORs 的 mRNA 水平，而 PAG 的刺激则产生相反的效果。上述结果表明，牙髓刺激显著上调了大鼠大脑中多种神经肽和三种类型的 ORs 的 mRNA 水平，从而导致更强的镇痛作用。相反，PAG 刺激下调了脑组织中几种神经肽和 ORs 的 mRNA 水平，从而导致 ORs 的合成减少。这些结果代表了对口面疼痛机制的新认识。
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