Regulation of excitatory ion channels in spinal cord dorsal horn pain signalling

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The dorsal horn of the spinal cord is an essential component of the pain transmission pathway. The outer layers of the dorsal horn process information from peripheral pain sensing neurons and relay integrated signals up to brain pain centers. Enhanced dorsal horn output underlies pain hypersensitivity in many chronic pain conditions, and yet the molecular and cellular mechanisms which cause this spinal cord dysfunction are poorly understood. The excitability of individual dorsal horn neurons is controlled by a balance between neuronal excitation (the "gas pedal" for pain sensation) and inhibition (the "brake pedal" for pain sensation), with shifts in this balance leading to hyperexcitability and pathological pain. We will study the role of electrical proteins, called ion channels, in regulating neuronal excitation within the spinal cord dorsal horn. Different types of dorsal horn neurons play different roles in spinal cord pain processing and we will investigate how variations in ion channel activity enable this specialization within the pain signalling network. To accomplish this, we will study the activity of specific types of ion channels in rodent spinal cord neurons through a combination of electrical recordings and molecular, biochemical and pharmacological techniques. Our research team will then investigate the molecular and cellular signalling mechanisms that increase excitatory ion channel activity to cause enhanced spinal cord excitation and pain hypersensitivity. Susceptibility to spinal cord hyperexcitability and chronic pain increases with age. We will identify how changes in ion channel expression and function contribute to the increased prevalence of chronic pain at later stages of development. Thus, our research program will provide critical information for understanding spinal pain processing, including how molecular changes in the pain signalling network can lead to pathological pain. These discoveries will help identify which pain-producing molecules are best suited as potential targets for new pain treatments. Our ultimate goal is to partner with industry to translate these findings into biomedical innovation which will help the millions of Canadians suffering from poorly-managed pain. The training of scientists throughout this research program will provide Canada with highly skilled workers equipped for careers in industrial, academic, health, and government professions. These personnel will increase Canada’s competitiveness in a knowledge-based global economy.