Bereiter D A, Bereiter D F
Department of Neuroscience, Brown University School of Medicine, 222 Nursing Arts Building, Rhode Island Hospital, Providence, USA.
Pain. 2000 Mar;85(1-2):65-77. doi: 10.1016/s0304-3959(99)00246-8.
Pain management in temporomandibular disorders (TMDs) often involves pharmacotherapy; however, the site of action for drugs that reduce TMD pain is not known. To determine possible central neural targets of analgesic drugs relevant in TMD pain, morphine or the N-methyl-D-aspartate receptor antagonist, MK-801, was given alone or in combination prior to TMJ injury. The number of neurons expressing the immediate early gene, c-fos, was quantified in the lower brainstem and upper cervical spinal cord as an index of neural activation. It was hypothesized that those neuronal groups most necessary for the sensory-discriminative aspects of acute TMJ injury should display the greatest reduction in c-fos expression after drug treatment. Barbiturate-anesthetized male rats were given morphine or MK-801 15 min prior to injection of mustard oil into the TMJ region. Morphine given centrally (i.c.v.) or peripherally (i.v.) caused a marked dose-related reduction in Fos-like immunoreactivity (Fos-LI) in laminae I-II at the middle portions of subnucleus caudalis (mid-Vc) and at the subnucleus caudalis/upper cervical spinal cord (Vc/C2) transition. Higher doses of morphine also reduced Fos-LI in the dorsal paratrigeminal region (dPa5) and at the subnucleus interpolaris/subnucleus caudalis (Vi/Vc-vl) transition. MK-801 given i.v. reduced Fos-LI only in laminae I-II at the Vc/C2 transition. Combined subthreshold doses of morphine and MK-801 reduced c-fos expression in the dPa5, mid-Vc, and the Vc/C2 transition region, below that predicted from the effects of either drug alone. These results suggest that neurons in laminae I-II of the mid-Vc and Vc/C2 transition and, to a lesser extent, in the dPa5 region play a critical role in mediating the sensory and/or reflex aspects of pain after acute injury to the TMJ region.
颞下颌关节紊乱病（TMDs）的疼痛管理通常涉及药物治疗；然而，减轻TMD疼痛的药物的作用位点尚不清楚。为了确定与TMD疼痛相关的镇痛药的可能中枢神经靶点，在颞下颌关节（TMJ）损伤前单独或联合给予吗啡或N-甲基-D-天冬氨酸受体拮抗剂MK-801。作为神经激活指标，对延髓下部和颈髓上部中表达即刻早期基因c-fos的神经元数量进行了量化。据推测，对于急性TMJ损伤的感觉辨别方面最必需的那些神经元群，在药物治疗后c-fos表达的降低应该最大。在将芥子油注射到TMJ区域前15分钟，给巴比妥麻醉的雄性大鼠给予吗啡或MK-801。中枢给予（脑室内注射）或外周给予（静脉注射）吗啡，在尾状核中部（Vc中部）的I-II层以及尾状核/颈髓上部（Vc/C2）交界处，引起Fos样免疫反应性（Fos-LI）显著的剂量相关性降低。更高剂量的吗啡还降低了三叉神经旁背侧区域（dPa5）以及极间核/尾状核（Vi/Vc-vl）交界处的Fos-LI。静脉注射MK-801仅在Vc/C2交界处的I-II层降低了Fos-LI。低于单独使用任何一种药物的效应所预测的值，亚阈值剂量的吗啡和MK-801联合使用降低了dPa5、Vc中部和Vc/C2过渡区域的c-fos表达。这些结果表明，Vc中部和Vc/C2交界处I-II层的神经元，以及在较小程度上dPa5区域的神经元，在介导TMJ区域急性损伤后疼痛的感觉和/或反射方面起关键作用。
