Tysseling V M, Klein D A, Imhoff-Manuel R, Manuel M, Heckman C J, Tresch M C
Department of Physical Therapy and Human Movement Sciences, Northwestern University, Chicago, Illinois;
Department of Physiology, Northwestern University, Chicago, Illinois.
J Neurophysiol. 2017 Nov 1;118(5):2944-2952. doi: 10.1152/jn.00190.2017. Epub 2017 Sep 6.
After spinal cord injury (SCI), reflexes become hyperexcitable, leading to debilitating muscle spasms and compromised motor function. Previous work has described adaptations in spinal systems that might underlie this hyperexcitability, including an increase in constitutively active 5-HT receptors in spinal motoneurons. That work, however, examined adaptations following complete transection SCI, whereas SCI in humans is usually anatomically and functionally incomplete. We therefore evaluated whether constitutive activity of 5-HT receptors contributes to reflex hyperexcitability in an incomplete compression model of SCI and to spasms in vitro and in vivo. Our results confirm that 5-HT receptor constitutive activity contributes to reflex excitability after incomplete SCI. We also evaluated whether constitutive activity could be altered by manipulation of neural activity levels after SCI, testing the hypothesis that it reflects homeostatic processes acting to maintain spinal excitability. We decreased neural activity after SCI by administering baclofen and increased activity by administering the selective serotonin reuptake inhibitor (SSRI) fluoxetine. We found that drug administration produced minimal alterations in in vivo locomotor function or reflex excitability. Similarly, we found that neither baclofen nor fluoxetine altered the contribution of constitutively active 5-HT receptors to reflexes after SCI, although the contribution of 5-HT receptors to reflex activity was altered after SSRIs. These results confirm the importance of constitutive activity in 5-HT receptors to spinal hyperexcitability following SCI in the clinically relevant case of incomplete SCI but suggest that this activity is not driven by homeostatic processes that act to maintain overall levels of spinal excitability. After spinal cord injury (SCI), most people will develop muscle spasms below their level of injury that can severely impact function. In this work, we examine the adaptations that occur within the spinal cord after SCI that contribute to these motor dysfunctions. We also evaluate one hypothesis about how these adaptations develop, which will potentially lead to intervention strategies to improve functional outcomes in persons with SCI.
脊髓损伤（SCI）后，反射会变得过度兴奋，导致使人衰弱的肌肉痉挛和运动功能受损。先前的研究描述了脊髓系统中的适应性变化，这些变化可能是这种过度兴奋的基础，包括脊髓运动神经元中组成型活性5-羟色胺（5-HT）受体的增加。然而，该研究考察的是完全横断性脊髓损伤后的适应性变化，而人类的脊髓损伤在解剖学和功能上通常是不完全的。因此，我们评估了5-HT受体的组成型活性是否会导致不完全性压迫性脊髓损伤模型中的反射性过度兴奋以及体外和体内的痉挛。我们的结果证实，5-HT受体的组成型活性会导致不完全性脊髓损伤后的反射兴奋性增加。我们还评估了脊髓损伤后通过操纵神经活动水平是否可以改变组成型活性，并检验了该活性反映维持脊髓兴奋性的稳态过程这一假设。我们通过给予巴氯芬降低脊髓损伤后的神经活动，并通过给予选择性5-羟色胺再摄取抑制剂（SSRI）氟西汀增加神经活动。我们发现药物给药对体内运动功能或反射兴奋性产生的改变极小。同样，我们发现，尽管SSRI给药后5-HT受体对反射活动的贡献发生了改变，但巴氯芬和氟西汀均未改变脊髓损伤后组成型活性5-HT受体对反射的贡献。这些结果证实了在临床上相关的不完全性脊髓损伤病例中，5-HT受体的组成型活性对脊髓损伤后脊髓过度兴奋的重要性，但表明这种活性并非由维持脊髓兴奋性总体水平的稳态过程所驱动。脊髓损伤（SCI）后，大多数人会在损伤平面以下出现肌肉痉挛，这会严重影响功能。在这项研究中，我们研究了脊髓损伤后脊髓内发生的导致这些运动功能障碍的适应性变化。我们还评估了一种关于这些适应性变化如何发生的假设，这可能会带来改善脊髓损伤患者功能结局的干预策略。
