Wasner Gunnar, Lee Bonsan Bonne, Engel Stella, McLachlan Elspeth
1Prince of Wales Medical Research Institute, University of New South Wales, Australia.
Brain. 2008 Sep;131(Pt 9):2387-400. doi: 10.1093/brain/awn169. Epub 2008 Jul 31.
Central neuropathic pain following lesions within the CNS, such as spinal cord injury, is one of the most excruciating types of chronic pain and one of the most difficult to treat. The role of spinothalamic pathways in this type of pain is not clear. Previous studies suggested that spinothalamic tract lesions are necessary but not sufficient for development of central pain, since deficits of spinothalamic function were equally severe in spinal cord injured people with and without pain. The aim of the present study was to examine spinothalamic tract function by quantitative sensory testing before and after activation and sensitization of small diameter afferents by applying menthol, histamine or capsaicin to the distal skin areas where spontaneous pain was localized. Investigations were performed in matched groups each of 12 patients with and without central pain below the level of a clinically complete spinal cord injury, and in 12 able-bodied controls. To test peripheral C fibre function, axon reflex vasodilations induced by histamine and capsaicin applications were quantified. In eight patients with pain, sensations of the same quality as one of their major individual pain sensations were rekindled by heat stimuli in combination with topical capsaicin (n = 7) or by cold stimuli (n = 1). No sensations were evoked in pain-free patients (P < 0.01). Capsaicin-induced axon reflex vasodilations were significantly larger in pain patients with heat- and capsaicin-evoked sensations in comparison to pain patients without capsaicin-provoked sensations. These results suggest that intact thermosensitive nociceptive afferents within lesioned spinothalamic tract pathways distinguish people with central pain from those without. The ability to mimic chronic pain sensations by activation of thermosensory nociceptive neurons implies that ongoing activity in these residual spinothalamic pathways plays a crucial role in maintaining central pain. We propose that processes associated with degeneration of neighbouring axons within the tract, such as inflammation, may trigger spontaneous activity in residual intact neurons that act as a 'central pain generator' after spinal cord injury.
中枢神经系统（CNS）损伤后出现的中枢神经性疼痛，如脊髓损伤后引发的疼痛，是最令人痛苦的慢性疼痛类型之一，也是最难治疗的疼痛之一。脊髓丘脑束通路在这类疼痛中所起的作用尚不清楚。先前的研究表明，脊髓丘脑束损伤对于中枢性疼痛的发生是必要但不充分的条件，因为在有疼痛和无疼痛的脊髓损伤患者中，脊髓丘脑束功能缺陷同样严重。本研究的目的是通过定量感觉测试，在向自发疼痛部位的远端皮肤区域涂抹薄荷醇、组胺或辣椒素激活并致敏小直径传入神经之前和之后，检测脊髓丘脑束的功能。研究对象为匹配的三组人群，每组各有12例在临床完全性脊髓损伤平面以下有或无中枢性疼痛的患者，以及12名健康对照者。为了测试外周C纤维功能，对组胺和辣椒素涂抹后诱发的轴突反射性血管舒张进行了量化。在8例疼痛患者中，热刺激联合局部辣椒素（n = 7）或冷刺激（n = 1）可重现与其主要个体疼痛感觉之一性质相同的感觉。无痛患者未诱发此类感觉（P < 0.01）。与未由辣椒素诱发感觉的疼痛患者相比，有热刺激和辣椒素诱发感觉的疼痛患者中，辣椒素诱发的轴突反射性血管舒张明显更大。这些结果表明，受损脊髓丘脑束通路内完整的热敏伤害性传入神经可区分有中枢性疼痛和无中枢性疼痛的人群。通过激活热感觉伤害性神经元来模拟慢性疼痛感觉的能力意味着，这些残余脊髓丘脑束通路中的持续活动在维持中枢性疼痛中起关键作用。我们提出，与该束内相邻轴突退变相关的过程，如炎症，可能触发残余完整神经元的自发活动，这些神经元在脊髓损伤后充当“中枢性疼痛发生器”。
