Zhang S, Chiang C Y, Xie Y F, Park S J, Lu Y, Hu J W, Dostrovsky J O, Sessle B J
Faculty of Dentistry, University of Toronto, 124 Edward Street, Toronto, Ontario, Canada M5G 1G6.
Neuroscience. 2006 Oct 27;142(3):833-42. doi: 10.1016/j.neuroscience.2006.06.063. Epub 2006 Aug 24.
We have recently demonstrated that application of mustard oil (MO), a small-fiber excitant and inflammatory irritant, to the rat maxillary molar tooth pulp induces central sensitization that is reflected in changes in spontaneous activity, mechanoreceptive field (RF) size, mechanical activation threshold, and responses to graded mechanical stimuli applied to the neuronal RF in trigeminal brainstem subnucleus caudalis and subnucleus oralis. The aim of this study was to test whether central sensitization can be induced in nociceptive neurons of the posterior thalamus by MO application to the pulp. Single unit neuronal activity was recorded in the ventroposterior medial nucleus (VPM) or posterior nuclear group (PO) of the thalamus in anesthetized rats, and nociceptive neurons were classified as wide dynamic range (WDR) or nociceptive-specific (NS). MO application to the pulp was studied in 47 thalamic nociceptive neurons and found to excite over 50% of the 35 VPM neurons tested and to produce significant long-lasting (over 40 min) increases in spontaneous activity, cutaneous pinch RF size and responses to graded mechanical stimuli, and a decrease in threshold in the 29 NS neurons tested; a smaller but statistically significant increase in mean spontaneous firing rate and decrease in activation threshold occurred following MO in the six WDR neurons tested. Vehicle application to the pulp did not produce any significant changes in six VPM NS neurons tested. MO application to the pulp produced pronounced increases in spontaneous activity, pinch RF size, and responses to mechanical stimuli, and a decrease in threshold in three of the six PO neurons. In conclusion, application of the inflammatory irritant MO to the tooth pulp results in central sensitization of thalamic nociceptive neurons and this neuronal hyperexcitability likely contributes to the behavioral consequences of peripheral inflammation manifesting as pain referral, hyperalgesia and allodynia.
我们最近证实，将芥子油（MO）——一种小纤维刺激剂和炎性刺激物——应用于大鼠上颌磨牙牙髓，会诱发中枢敏化，这表现为自发活动、机械感受野（RF）大小、机械激活阈值的变化，以及对三叉神经脑干尾侧亚核和口侧亚核中神经元RF施加的分级机械刺激的反应变化。本研究的目的是测试通过将MO应用于牙髓是否能在丘脑后部的伤害性神经元中诱发中枢敏化。在麻醉大鼠的丘脑腹后内侧核（VPM）或后核群（PO）中记录单个单位神经元活动，伤害性神经元被分类为广动力范围（WDR）或伤害性特异（NS）神经元。在47个丘脑伤害性神经元中研究了将MO应用于牙髓的情况，发现其能兴奋所测试的35个VPM神经元中的50%以上，并使所测试的29个NS神经元的自发活动、皮肤夹捏RF大小和对分级机械刺激反应产生显著的长期（超过40分钟）增加，阈值降低；在所测试的6个WDR神经元中，MO应用后平均自发放电率有较小但具有统计学意义的增加，激活阈值降低。对牙髓应用赋形剂，在所测试的6个VPM NS神经元中未产生任何显著变化。对牙髓应用MO，使6个PO神经元中的3个的自发活动、夹捏RF大小和对机械刺激的反应显著增加，阈值降低。总之，将炎性刺激物MO应用于牙髓会导致丘脑伤害性神经元的中枢敏化，这种神经元的过度兴奋可能导致外周炎症的行为后果，表现为疼痛牵涉、痛觉过敏和异常性疼痛。
