How is the spinal cord influenced by peripheral nerve injury?
Peripheral nerve injury was originally thought to only functionally disconnect the periphery from the spinal cord. Because the dorsal root ganglion is not injured when the peripheral nerve is damaged, neither anatomical nor biochemical changes in the proximal limb of the dorsal root or in the dorsal horn were expected. In fact, we now know that there are changes in the dorsal root ganglia and in the spinal cord neurons with which they are connected.
Among the changes is a significant decrease in the concentration of substance P message and substance P peptide in neurons of the dorsal root ganglia. In addition, substance P levels are decreased in the terminals of primary afferent fibers in the dorsal horn. Significant changes also in postsynaptic dorsal horn neurons.
The electrophysiological consequences of peripheral nerve injury are also profound. A massive release of glutamate acts on NMDA receptors to produce long-term changes in the properties of the dorsal horn neurons. Central sensitization (i.e., hyperexcitability) of dorsal horn neurons in the setting of injury is particularly common and may contribute to postinjury pain states. Peripheral nerve injury also induces a loss of inhibitory controls, by reducing the action of GABAergic inhibitory interneurons. This produces an epileptic-like condition that likely contribute to the ongoing burning pain and the allodynia and hyperalgesia in neuropathic pain conditions. It is not surprising, therefore, that anticonvulsants, such as gabapentinoids, are the first-line therapy for neuropathic pain. Most recently preclinical studies have demonstrated that dorsal horn transplantation of embryonic precursors of cortical GABAergic interneurons can ameliorate mechanical hypersensitivity produced by peripheral nerve injury.
