The mechanisms underlying sensory dysfunction in human pain channelopathies

Neuropathic pain is a common disabling pain state arising from injury to the sensory nervous system. Enhanced activity of sensory neurons, with lowered activation thresholds and spontaneous activity, is a key driver of neuropathic pain. Ion channels are proteins which regulate neuronal excitability. Rare inherited ion channel mutations can result in either reduced or increased pain sensitivity. Ion channel variants have also been linked with more common acquired neuropathic pain conditions such as painful neuropathy.

I will define the mechanisms by which mutations in ion channels alter the excitability of sensory neurons by studying how sensory stimuli are detected, transmitted and communicated by sensory neurons to other neurons. This will be achieved by studying patients with ion channel mutations to understand their perception of different sensory stimuli. I will develop models using cells derived from these patients in which ion channel function can be directly assessed. I will also develop animal models which mirror these same mutations.

My aim is to provide insight into how ion channels control sensory neuron excitability. This will aid diagnosis and management of rare inherited pain disorders and more common conditions such as painful diabetic neuropathy.