Department of Neurosurgery, Neuroscience Center of Excellence, Louisiana State University Health Sciences Center, New Orleans, Louisiana 70112, USA.
Neurosurgery. 2011 Apr;68(4):1048-55; discussion 1055. doi: 10.1227/NEU.0b013e318208f9c4.
Neurotrophin-3 (NT3) and its cognate receptor, tyrosine kinase C (TrkC), have recently been shown to modulate neuropathic pain. Another receptor, the transient receptor potential vanilloid 1, is considered a molecular integrator for nociception. Transient receptor potential vanilloid 1-positive cells can be selectively ablated by Resiniferatoxin (RTX). NT3 changes in the dorsal root ganglia (DRG) after RTX treatment may further define their role in pain modulation.
To demonstrate the role of NT3 and TrkC in intraganglial RTX-induced pain suppression and in neuropathic pain development.
Fifty-three rats underwent a photochemical left sciatic nerve injury. Neuropathic animals were treated by RTX injection in the ipsilateral L3-6 DRG. NT3 and TrkC presence in the DRG was evaluated before and after the nerve injury, as well as after RTX treatment.
The RTX injection resulted in pain inhibition. NT3 normally expressed mainly in large- and medium-size neurons. NT3 presence was increased mainly in the small DRG cells of neuropathic animals, and the medium- and large-size neurons of nonallodynic rats. RTX treatment of allodynic rats changed the NT3 distribution to a nonallodynic pattern. TrkC expressed mainly in large/medium-size neurons. After nerve injury, TrkC expression was also increased in the small DRG cells of allodynic animals (although less than NT3), and the medium- and large-size cells of nonallodynic ones. After RTX, TrkC expression gradually decreased, but with persistence in the large DRG cells.
NT3 may have antinociceptive effects in the DRG. These effects may be mediated, at least in part, by TrkC in the medium- and large-size DRG neurons.
神经生长因子-3（NT3）及其同源受体酪氨酸激酶 C（TrkC）最近被证明可调节神经病理性疼痛。另一种受体，香草素瞬时受体电位 1（TRPV1），被认为是伤害感受的分子整合器。香草素瞬时受体电位 1 阳性细胞可被树脂毒素（RTX）选择性消融。DRG 中 RTX 处理后 NT3 的变化可能进一步定义其在疼痛调节中的作用。
证明 NT3 和 TrkC 在 DRG 内 RTX 诱导的疼痛抑制和神经病理性疼痛发展中的作用。
53 只大鼠行光化学性左侧坐骨神经损伤。神经病理性动物通过在同侧 L3-6 DRG 注射 RTX 进行治疗。在神经损伤前后以及 RTX 治疗后评估 DRG 中的 NT3 和 TrkC 存在情况。
RTX 注射导致疼痛抑制。NT3 通常主要在大、中神经元中表达。NT3 的存在主要在神经病理性动物的小 DRG 细胞中增加，而在非痛觉过敏大鼠的中、大神经元中增加。RTX 治疗痛觉过敏大鼠使 NT3 分布改变为非痛觉过敏模式。TrkC 主要在大/中神经元中表达。神经损伤后，痛觉过敏动物的小 DRG 细胞中 TrkC 表达也增加（尽管少于 NT3），而非痛觉过敏动物的中、大神经元中表达也增加。RTX 后，TrkC 表达逐渐下降，但在大 DRG 细胞中仍有持续存在。
NT3 可能在 DRG 中具有抗伤害感受作用。这些作用至少部分可能通过中等和大 DRG 神经元中的 TrkC 介导。
