Gasull Xavier, Liao Xiaogang, Dulin Michael F, Phelps Cynthia, Walters Edgar T
Department of Integrative Biology and Pharmacology, University of Texas-Houston Medical School, Houston, Texas, USA.
J Neurophysiol. 2005 Sep;94(3):2218-30. doi: 10.1152/jn.00169.2005. Epub 2005 Jun 8.
Peripheral axotomy induces long-term hyperexcitability (LTH) of centrally located sensory neuron (SN) somata in diverse species. In mammals this LTH can promote spontaneous activity of pain-related SNs, and such activity may contribute to neuropathic pain and hyperalgesia. However, few axotomized SN somata begin to fire spontaneously in any species, and why so many SNs display soma LTH after axotomy remains a mystery. Is soma LTH a side effect of injury with pathological but no adaptive consequences, or was this response selected during evolution for particular functions? A hypothesis for one function of soma LTH in nociceptive SNs in Aplysia californica is proposed: after peripheral injury that produces partial axotomy of some SNs, compensation for sensory deficits and protective sensitization are achieved by facilitating afterdischarge near the soma, which amplifies sensory input from injured peripheral fields. Four predictions of this hypothesis were confirmed in SNs that innervate the tail. First, LTH of SN somata was induced by a relatively natural axotomizing event-a small cut across part of the tail in the absence of anesthesia. Second, soma LTH was selectively expressed in SNs having axons in cut or crushed nerves rather than nearby, uninjured nerves. Third, after several weeks soma LTH began to reverse when functional recovery of the interrupted afferent pathway was shown by reestablishment of a centrally mediated siphon reflex. Fourth, axotomized SNs developed central afterdischarge that amplified sensory discharge coming from the periphery, and the after-depolarization underlying this afterdischarge was enhanced by previous axotomy.
外周轴突切断术可诱导多种物种中枢感觉神经元（SN）胞体产生长期的兴奋性增强（LTH）。在哺乳动物中，这种LTH可促进与疼痛相关的SN的自发活动，而这种活动可能导致神经性疼痛和痛觉过敏。然而，在任何物种中，很少有轴突切断的SN胞体开始自发放电，轴突切断后为何如此多的SN显示胞体LTH仍是一个谜。胞体LTH是损伤的副作用，具有病理但无适应性后果，还是这种反应在进化过程中因特定功能而被选择？本文提出了一个关于加州海兔伤害性SN中胞体LTH的一种功能的假说：在导致一些SN部分轴突切断的外周损伤后，通过促进胞体附近的后放电来实现对感觉缺陷的补偿和保护性致敏，这会放大来自受伤外周区域的感觉输入。在支配尾巴的SN中证实了该假说的四个预测。第一，SN胞体的LTH是由相对自然的轴突切断事件诱导的——在无麻醉的情况下对尾巴部分进行小切口。第二，胞体LTH选择性地在轴突位于切断或挤压神经而非附近未受伤神经中的SN中表达。第三，几周后，当通过重新建立中枢介导的虹吸反射显示中断的传入通路功能恢复时，胞体LTH开始逆转。第四，轴突切断的SN产生中枢后放电，放大来自外周的感觉放电，并且这种后放电背后的去极化后电位因先前的轴突切断而增强。
