Fauss Gizelle N K, Hudson Kelsey E, Grau James W
Department of Psychological and Brain Sciences, Texas A&M University, College Station, TX 77843, USA.
Biology (Basel). 2022 Feb 1;11(2):234. doi: 10.3390/biology11020234.
As the nervous system develops, nerve fibers from the brain form descending tracts that regulate the execution of motor behavior within the spinal cord, incoming sensory signals, and capacity to change (plasticity). How these fibers affect function depends upon the transmitter released, the receptor system engaged, and the pattern of neural innervation. The current review focuses upon the neurotransmitter serotonin (5-HT) and its capacity to dampen (inhibit) neural excitation. A brief review of key anatomical details, receptor types, and pharmacology is provided. The paper then considers how damage to descending serotonergic fibers contributes to pathophysiology after spinal cord injury (SCI). The loss of serotonergic fibers removes an inhibitory brake that enables plasticity and neural excitation. In this state, noxious stimulation can induce a form of over-excitation that sensitizes pain (nociceptive) circuits, a modification that can contribute to the development of chronic pain. Over time, the loss of serotonergic fibers allows prolonged motor drive (spasticity) to develop and removes a regulatory brake on autonomic function, which enables bouts of unregulated sympathetic activity (autonomic dysreflexia). Recent research has shown that the loss of descending serotonergic activity is accompanied by a shift in how the neurotransmitter GABA affects neural activity, reducing its inhibitory effect. Treatments that target the loss of inhibition could have therapeutic benefit.
随着神经系统的发育，来自大脑的神经纤维形成下行束，调节脊髓内运动行为的执行、传入的感觉信号以及变化（可塑性）的能力。这些纤维如何影响功能取决于释放的递质、参与的受体系统以及神经支配模式。本综述聚焦于神经递质5-羟色胺（5-HT）及其抑制神经兴奋的能力。文中简要回顾了关键的解剖学细节、受体类型和药理学。接着本文探讨了下行5-羟色胺能纤维受损如何导致脊髓损伤（SCI）后的病理生理学变化。5-羟色胺能纤维的丧失消除了一种抑制性制动，这种制动能使可塑性和神经兴奋得以发生。在这种状态下，有害刺激可诱发一种过度兴奋形式，使疼痛（伤害性感受）回路敏感化，这种改变可能导致慢性疼痛的发展。随着时间的推移，5-羟色胺能纤维的丧失会导致长时间的运动驱动（痉挛）发展，并消除对自主神经功能的调节性制动，从而引发不受控制的交感神经活动发作（自主神经反射异常）。最近的研究表明，下行5-羟色胺能活动的丧失伴随着神经递质γ-氨基丁酸（GABA）影响神经活动方式的转变，降低了其抑制作用。针对抑制作用丧失的治疗可能具有治疗益处。
