Ralston Henry J
Department of Anatomy, W. M. Keck Foundation Center for Integrative Neuroscience, University of California, San Francisco, CA 94143-0452, USA.
Prog Brain Res. 2005;149:1-10. doi: 10.1016/S0079-6123(05)49001-9.
Noxious stimuli that are perceived as painful, are conveyed to the thalamus by the spinothalamic tract (STT) and the spinotrigeminothalamic tracts (vSTT), arising from the dorsal horn of the spinal cord and medulla, respectively. Most investigators have concluded that the thalamic terminus of these pathways include several nuclei of the somatosensory and intralaminar thalamus. Non-noxious stimuli are carried by the dorsal column/medial lemniscal or the trigeminothalamic pathways which terminate in much more restricted regions of the thalamus than do the STT and vSTT systems. Lesions of components of the somatosensory pathways result in profound changes in the circuitry of the recipient thalamic nuclei. Not only are there the expected losses of the injured axons and their synaptic terminations, but there is also a marked reduction of the intrinsic GABAergic circuitry, even though the GABAergic neurons contributing to the circuitry have not been injured directly by lesions of the afferent pathways. Such changes in the inhibitory circuitry observed in experimental animals may explain the abnormal bursting behavior of thalamic neurons found in patients with central deafferentation pain syndromes. One potential approach to treating chronic pain would be to selectively remove the neurons of the superficial dorsal horn (lamina I) that specifically respond to noxious stimuli (NS neurons). A toxin has been developed (SSP saporin) that binds to the substance P receptor of NS neurons, is internalized by the neuron and kills the cell. SSP saporin has been shown to be effective in rats, and we have recently demonstrated that it effectively causes lesions in NS neurons of the lumbar spinal cord in the monkey and reduces the animals' response to noxious cutaneous stimuli. The SSP-saporin administration to the lumbar spinal cord destroys a relatively small number of the total neurons that project into the somatosensory thalamus and does not lead to demonstrable changes in the inhibitory circuitry of the thalamus, in contrast to lesions of major pathways that lead to reductions in the thalamic inhibitory circuitry.
被感知为疼痛的有害刺激，分别通过脊髓背角和延髓发出的脊髓丘脑束（STT）和脊髓三叉丘脑束（vSTT），传递至丘脑。大多数研究人员得出结论，这些通路在丘脑的终点包括体感丘脑和板内核丘脑的几个核团。无害刺激由背柱/内侧丘系或三叉丘脑通路传导，这些通路在丘脑的终止区域比STT和vSTT系统更为局限。体感通路各组成部分的损伤会导致接受刺激的丘脑核团回路发生深刻变化。不仅受损轴突及其突触终末会出现预期的损失，而且即使构成该回路的γ-氨基丁酸能神经元并未因传入通路的损伤而直接受损，其内在的γ-氨基丁酸能回路也会显著减少。在实验动物中观察到的这种抑制性回路变化，可能解释了中枢性去传入性疼痛综合征患者丘脑神经元的异常爆发行为。一种治疗慢性疼痛的潜在方法是选择性地去除浅表背角（I层）中对有害刺激有特异性反应的神经元（NS神经元）。已经开发出一种毒素（SSP皂草素），它能与NS神经元的P物质受体结合，被神经元内化并杀死细胞。SSP皂草素已在大鼠身上显示出有效性，并且我们最近证明它能有效损伤猴子腰脊髓中的NS神经元，并降低动物对有害皮肤刺激的反应。与导致丘脑抑制性回路减少的主要通路损伤相反，向腰脊髓注射SSP皂草素只会破坏投射到体感丘脑的神经元总数中的相对少数，且不会导致丘脑抑制性回路出现明显变化。
