Defining the Diversity of Pain Processing Neurons in the Spinal Cord
The superficial dorsal horn (SDH) of the spinal cord is responsible for the relaying of all pain information from the periphery up to the brain where it becomes part of our sensory experience. However, the neurons in these layers do not just serve as a relay station, but also as a hub. The vast majority of neurons in these layers are actually interneurons that receive and process pain information, in a complicated network of excitatory and inhibitory communication. The exact function and structure of this network is still being investigated, however deficits in inhibition and overexcitation have been implicated in the manifestation of clinical chronic pain symptoms.
To understand the changes in these neurons that lead to loss of inhibition and overexcitation, we must understand the types of neurons involved in this SDH neuronal network. One of the ways that scientists have classically differentiated SDH neuron subpopulations is based on the pattern of action potential firing that they display in response to a large depolarizing input. For example, tonic firing pattern (neurons that fire at a constant rate for the entire duration of depolarization) neurons are more likely to be inhibitory neurons. An active question in the field is why these neurons have different action potential firing patterns, and what purpose these different subpopulations of neurons could serve. In this paper, UTCSP scientist Dr. Steve Prescott and UofT med student Arjun Balachandar investigate the mechanisms of these different firing patterns.
The authors use computational modelling to simulate different action potential firing patterns, and find that they can switch between firing patterns simply by changing the numbers of potassium ion channels present. They found multiple combinations that would simulate the same firing pattern. This implies that the same firing patterns could arise from many different combinations of ion channel expression, suggesting that caution should be taken in assuming that SDH neurons with the same firing pattern are all part of the same subpopulation with the same molecular properties and same function in pain processing and transmission.
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Reference: Balachandar A, Prescott, SA. (2018). Origin of heterogeneous spiking patterns from continuously distributed ion channel densities: a computational study in spinal dorsal horn neurons. J. Physiol. Epub ahead of print.