School of Biomedical Sciences and Pharmacy, University of Newcastle, Callaghan, NSW 2308, Australia.
J Physiol. 2012 May 15;590(10):2409-25. doi: 10.1113/jphysiol.2012.227389. Epub 2012 Feb 20.
Neurons in the superficial dorsal horn (SDH; laminae I-II) of the spinal cord process nociceptive information from skin, muscle, joints and viscera. Most of what we know about the intrinsic properties of SDH neurons comes from studies in lumbar segments of the cord even though clinical evidence suggests nociceptive signals from viscera and head and neck tissues are processed differently. This ‘lumbar-centric' view of spinal pain processing mechanisms also applies to developing SDH neurons. Here we ask whether the intrinsic membrane properties of SDH neurons differ across spinal cord segments in both the developing and mature spinal cord. Whole cell recordings were made from SDH neurons in slices of upper cervical (C2-4), thoracic (T8-10) and lumbar (L3-5) segments in neonatal (P0-5) and adult (P24-45) mice. Neuronal input resistance (R(IN)), resting membrane potential, AP amplitude, half-width and AHP amplitude were similar across spinal cord regions in both neonates and adults (∼100 neurons for each region and age). In contrast, these intrinsic membrane properties differed dramatically between neonates and adults. Five types of AP discharge were observed during depolarizing current injection. In neonates, single spiking dominated (∼40%) and the proportions of each discharge category did not differ across spinal regions. In adults, initial bursting dominated in each spinal region, but was significantly more prevalent in rostral segments (49% of neurons in C2-4 vs. 29% in L3-5). During development the dominant AP discharge pattern changed from single spiking to initial bursting. The rapid A-type potassium current (I(Ar)) dominated in neonates and adults, but its prevalence decreased (∼80% vs. ∼50% of neurons) in all regions during development. I(Ar) steady state inactivation and activation also changed in upper cervical and lumbar regions during development. Together, our data show the intrinsic properties of SDH neurons are generally conserved in the three spinal cord regions examined in both neonate and adult mice. We propose the conserved intrinsic membrane properties of SDH neurons along the length of the spinal cord cannot explain the marked differences in pain experienced in the limbs, viscera, and head and neck.
脊髓背角浅层(SDH;I-II 层)中的神经元处理来自皮肤、肌肉、关节和内脏的痛觉信息。我们对 SDH 神经元固有特性的了解主要来自于脊髓腰段的研究,尽管临床证据表明来自内脏和头颈部组织的痛觉信号的处理方式不同。这种脊髓疼痛处理机制的“以腰段为中心”的观点也适用于发育中的 SDH 神经元。在这里,我们研究了在发育中和成熟的脊髓中,SDH 神经元的内在膜特性是否在不同的脊髓节段有所不同。在新生(P0-5)和成年(P24-45)小鼠的颈上(C2-4)、胸(T8-10)和腰(L3-5)段的切片上,通过全细胞膜片钳记录了 SDH 神经元的电流。在新生和成年小鼠中,神经元输入电阻(R(IN))、静息膜电位、AP 幅度、半宽度和 AHP 幅度在脊髓各区域相似(每个区域和年龄约 100 个神经元)。相比之下,这些内在的膜特性在新生和成年动物之间有很大的差异。在去极化电流注入期间观察到 5 种 AP 放电类型。在新生动物中,单峰放电占主导地位(约 40%),并且每个放电类别的比例在脊髓区域之间没有差异。在成年动物中,初始爆发占主导地位,但在头段更为明显(C2-4 中的神经元中有 49%,而 L3-5 中的神经元有 29%)。在发育过程中,主导的 AP 放电模式从单峰放电转变为初始爆发。快速 A 型钾电流(I(Ar))在新生和成年动物中占主导地位,但在所有区域的发育过程中,其普遍性下降(约 80%对约 50%的神经元)。I(Ar)稳态失活和激活也在上颈段和腰段发育过程中发生了变化。总的来说,我们的数据表明,在新生和成年小鼠的三个脊髓区域中,SDH 神经元的内在特性通常是保守的。我们提出,脊髓中 SDH 神经元的固有膜特性在长度上的保守性不能解释肢体、内脏和头颈部疼痛感觉的显著差异。