Glutamic acid as a synaptic transmitter candidate in the dorsal sensory neuron: Reconsiderations

Abstract

Two primary reasons which are emerging to suggest that glutamate is not a dorsal root transmitter are: 1) that free glutamate levels in the dorsal root vs. the ventral root are not sufficiently different to warrant a transmitter function in the dorsal root, and 2) the spinal cord glutamate levels do not significantly change (per g tissue) after dorsal root input section. Recent analyses suggest, however, that there is a highly significant depression of glutamate in the dorsal root when related to total free amino acid concentration changes after root injury. This is not seen in the peripheral nerve. Thus the dorsal vs. ventral root free glutamate concentration difference is highly significant metabolically. The failure to see a decrease in spinal cord gray glutamate levels after dorsal root section would appear to be explained by the fact that the spinal cord satellite cells and neurons have a higher free glutamate concentration than the entering dorsal roots along with a considerable perikaryal free amino acid pool for protein synthesis. This will mask any changes due to dorsal root section. Comparisons of excess free glutamate and substance P (the two leading dorsal root transmitter candidates) in the dorsal root compared to the ventral root have shown that there is a much larger excess of free glutamate in the dorsal root. This is true, even when considering the excitatory potency differences of these two substances. Thus, a very large free glutamate excess in the dorsal root is present with a relatively small concentration difference compared to the ventral root (where a transmitter role is not entertained). This fact could be of considerable metabolic significance in the regulation of transmitter levels of glutamate. The data available, therefore, are supportive of a possible glutamate transmitter role in a population of dorsal root fibers.