Paulson Pamela E, Casey Kenneth L, Morrow Thomas J
Neurology Research Laboratories, University of Michigan, Ann Arbor, MI 48105, USA.
Pain. 2002 Jan;95(1-2):31-40. doi: 10.1016/s0304-3959(01)00370-0.
We identified long-term (up to 12 weeks), bilateral changes in spontaneous and evoked pain behavior and baseline forebrain activity following a chronic constriction injury (CCI) of the sciatic nerve. The long-term changes in basal forebrain activation following CCI were region-specific and can be divided into forebrain structures that showed either: (1) no change, (2) an increase, or (3) a decrease in activity with regard to the short-term (2 weeks) changes we previously reported. All the rats showed spontaneous pain behaviors that persisted throughout the 12-week observation period, resembling the pattern of change found in four limbic system structures: the anterior dorsal thalamus, habenular complex, and the cingulate and retrosplenial cortices. In contrast, heat hyperalgesia was delayed in onset until 4 weeks following CCI, but then persisted, showing a nearly constant level of increased responsiveness. The forebrain activation that resembles this behavioral pattern of change is found in somatosensory cortex, and in the hypothalamic paraventricular nucleus and the basolateral amygdala. Finally, mechanical allodynia, which was maximal during the first 2 weeks following nerve injury and gradually recovered by the seventh post-operative week uniquely matches the time course of changes in ventrolateral and ventroposterolateral thalamic activity. Our results indicate that peripheral nerve damage results in persistent changes in behavior and resting forebrain systems that modulate pain perception. The persistent abnormalities in the somatosensory cortex and thalamus suggest that the sensory thalamocortical axis is functionally deranged in certain chronic pain states.
我们发现，坐骨神经慢性缩窄损伤（CCI）后，自发痛和诱发性疼痛行为以及前脑基线活动出现了长期（长达12周）的双侧变化。CCI后基底前脑激活的长期变化具有区域特异性，根据我们之前报道的短期（2周）变化，可分为以下几种前脑结构：（1）无变化；（2）活动增加；（3）活动减少。所有大鼠在整个12周的观察期内均表现出自发痛行为，类似于在四个边缘系统结构中发现的变化模式：背侧丘脑前部、缰核复合体以及扣带回和压后皮质。相比之下，热痛觉过敏在CCI后4周才开始出现，但随后持续存在，表现出几乎恒定的反应性增加水平。在躯体感觉皮层、下丘脑室旁核和基底外侧杏仁核中发现了与这种行为变化模式相似的前脑激活。最后，机械性异常性疼痛在神经损伤后的前2周最为严重，并在术后第7周逐渐恢复，这与腹外侧和腹后外侧丘脑活动的变化时间进程独特匹配。我们的结果表明，外周神经损伤导致行为和静息前脑系统的持续变化，这些系统调节痛觉。躯体感觉皮层和丘脑的持续异常表明，在某些慢性疼痛状态下，感觉丘脑皮质轴在功能上发生了紊乱。
