Baumbauer Kyle M, Young Erin E, Joynes Robin L
Department of Psychology, Texas A&M University, MS 4235, College Station, TX 77843, USA.
Brain Res Rev. 2009 Oct;61(2):124-43. doi: 10.1016/j.brainresrev.2009.05.004. Epub 2009 May 27.
The long-standing belief that the spinal cord serves merely as a conduit for information traveling to and from the brain is changing. Over the past decade, research has shown that the spinal cord is sensitive to response-outcome contingencies, demonstrating that spinal circuits have the capacity to modify behavior in response to differential environmental cues. If spinally transected rats are administered shock contingent on leg extension (controllable shock), they will maintain a flexion response that minimizes shock exposure. If, however, this contingency is broken, and shock is administered irrespective of limb position (uncontrollable shock), subjects cannot acquire the same flexion response. Interestingly, each of these treatments has a lasting effect on behavior; controllable shock enables future learning, while uncontrollable shock produces a long-lasting learning deficit. Here we suggest that the mechanisms underlying learning and the deficit may have evolved from machinery responsible for the spinal processing of noxious information. Experiments have shown that learning and the deficit require receptors and signaling cascades shown to be involved in central sensitization, including activation of NMDA and neurokinin receptors, as well as CaMKII. Further supporting this link between pain and learning, research has also shown that uncontrollable stimulation results in allodynia. Moreover, systemic inflammation and neonatal hindpaw injury each facilitate pain responding and undermine the ability of the spinal cord to support learning. These results suggest that the plasticity associated with learning and pain must be placed in a balance in order for adaptive outcomes to be observed.
长期以来认为脊髓仅仅是信息进出大脑的通道的观念正在改变。在过去十年中，研究表明脊髓对反应-结果的意外情况敏感，这表明脊髓回路有能力根据不同的环境线索改变行为。如果对脊髓横断的大鼠施加与腿部伸展相关的电击（可控电击），它们会保持一种使电击暴露最小化的屈曲反应。然而，如果这种意外情况被打破，且无论肢体位置如何都施加电击（不可控电击），实验对象就无法获得相同的屈曲反应。有趣的是，这些处理中的每一种对行为都有持久的影响；可控电击能促进未来的学习，而不可控电击则会产生长期的学习缺陷。在此我们认为，学习和缺陷背后的机制可能是从负责脊髓对有害信息处理的机制演变而来的。实验表明，学习和缺陷需要那些已被证明参与中枢敏化的受体和信号级联反应，包括NMDA和神经激肽受体的激活以及CaMKII。进一步支持疼痛与学习之间联系的是，研究还表明不可控刺激会导致痛觉过敏。此外，全身性炎症和新生儿后爪损伤都会促进疼痛反应，并损害脊髓支持学习的能力。这些结果表明，为了观察到适应性结果，与学习和疼痛相关的可塑性必须保持平衡。
