Tong Chi-Kun, MacDermott Amy B
Department of Physiology and Cellular Biophysics, Columbia University, 630 W. 168th St, Room 1109, New York, NY 10032, USA.
J Physiol. 2006 Aug 15;575(Pt 1):133-44. doi: 10.1113/jphysiol.2006.110072. Epub 2006 Jun 8.
Blockade of Ca2+-permeable AMPA receptors in the rat spinal cord diminishes the development of hyperalgesia and allodynia associated with peripheral injury. Cobalt uptake studies reveal that Ca2+-permeable AMPA receptors are expressed by some substance P receptor-expressing (NK1R+) neurons in lamina I, as well as other neurons throughout the superficial dorsal horn. Selective elimination of NK1R+ neurons in lamina I and lamina III/IV of the dorsal horn also suppresses development of hyperalgesia and allodynia. These observations raise the possibility that Ca2+-permeable AMPA receptors contribute to excitatory synaptic drive onto the NK1R+ neurons associated with allodynia and hyperalgesia. The first synapse in the pain pathway is the glutamatergic excitatory drive from the primary afferent fibres onto dorsal horn neurons. Therefore, we tested whether Ca2+-permeable AMPA receptors are located on lamina I and lamina III/IV NK1R+ neurons postsynaptic to primary afferent fibres, using inward rectification and polyamine toxins for receptor identification. We examined three different populations of dorsal horn neurons; lamina I NK1R+ neurons, including projection neurons, and non-NK1R+ (NK1R-) neurons including interneurons, and lamina III/IV NK1R+ neurons, believed to contribute to the low-threshold mechanosensory pathway. The majority of synapses in all three groups had rectification indices less than 1.0 and greater than 0.4, indicating that the AMPA receptors at these synapses are a mixture of Ca2+-permeable and -impermeable forms. Lamina III/IV NK1R+ neurons and lamina I NK1R- neurons have a significantly higher proportion of postsynaptic Ca2+-permeable AMPA receptors than lamina I NK1R+ neurons. Thus synaptically positioned Ca2+-permeable AMPA receptors directly contribute to low-threshold sensory afferent drive into the dorsal horn, and can mediate afferent input onto interneurons such as GABAergic neurons. These receptors also contribute to high-threshold primary afferent drive onto NK1R+ neurons in the superficial dorsal horn, but do so less consistently.
阻断大鼠脊髓中钙离子通透的AMPA受体可减少与外周损伤相关的痛觉过敏和异常性疼痛的发展。钴摄取研究表明，钙离子通透的AMPA受体由I层中一些表达P物质受体（NK1R+）的神经元以及整个浅背角的其他神经元表达。选择性消除背角I层和III/IV层中的NK1R+神经元也可抑制痛觉过敏和异常性疼痛的发展。这些观察结果提示，钙离子通透的AMPA受体可能参与了与异常性疼痛和痛觉过敏相关的对NK1R+神经元的兴奋性突触驱动。疼痛通路中的第一个突触是初级传入纤维对背角神经元的谷氨酸能兴奋性驱动。因此，我们使用内向整流和多胺毒素来鉴定受体，测试钙离子通透的AMPA受体是否位于初级传入纤维突触后I层和III/IV层的NK1R+神经元上。我们检查了三种不同类型的背角神经元；I层NK1R+神经元，包括投射神经元，以及非NK1R+（NK1R-）神经元，包括中间神经元，还有III/IV层NK1R+神经元，据信其参与低阈值机械感觉通路。所有三组中的大多数突触的整流指数小于1.0且大于0.4，表明这些突触处的AMPA受体是钙离子通透和不通透形式的混合物。III/IV层NK1R+神经元和I层NK1R-神经元的突触后钙离子通透的AMPA受体比例明显高于I层NK1R+神经元。因此，突触定位的钙离子通透的AMPA受体直接促进低阈值感觉传入驱动进入背角，并可介导传入输入到中间神经元，如GABA能神经元。这些受体也促进高阈值初级传入驱动到浅背角的NK1R+神经元，但作用不太一致。
