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Chronic pain affects millions worldwide, disrupting and diminishing quality of life. The drugs we use to treat chronic pain are often ineffective or have negative side effects, including addiction. Nonpharmacological alternatives such as electrical nerve or spinal cord stimulation have seen some success in relieving pain, with the clear advantage of fewer side effects.  However, the evidence for their effectiveness is conflicting. Of particular note, while spinal cord stimulation is indicated for neuropathic pain (damage to the nervous system itself), its efficacy in chronic nociceptive pain (e.g. arthritis) is significantly limited and the therapy is often misprescribed. This is important because chronic nociceptive pain is far more prevalent, presenting four to ten times as often in clinics compared to neuropathic pain alone.

This project aims to explore the use of a new type of technology, called freeform stimulation, that can deliver electrical current to neural targets via microfluidic electrolytic channels. We aim to develop a novel, drug-free therapy for chronic nociceptive pain by using ionic direct current (iDC) to selectively suppress nociceptive (pain-transmitting) nerve activity while preserving other neural functions such as touch. To achieve this we use a combination of advanced surgical and implantable materials design, chronic device safety, animal behaviour, and electrophysiology. We hope to establish a foundation for advancing this therapy toward clinical applications, improving the quality of life for chronic pain sufferers.

Glia are the support and immune cells of the nervous system. Dysfunction of glial cells is a key mechanism underlying chronic pain. Recent studies have suggested that the use of electrical waveforms in the spinal cord can help reduce inflammation and over-sensitivity of neural cells in the spine by changing (“modulating”) glial cell function. While current approaches use short, pulsed electricity, there has been no research on how constant (direct current) electricity could be similarly used. There is strong reason to believe direct current might be even better at controlling glial cells due to evidence from brain stimulation and experiments using immune cells outside of the body.

We aim to explore the potential to control glial cells in the spine. The missing piece of the puzzle lies in understanding how these direct current electrical waveforms can influence glial cell behaviour. By unravelling this mystery, we can pave the way for a new drug-free therapeutic approach that directly targets and controls glial cells to relieve chronic pain. We examine how glial and neural cells in the spinal cord change their behaviour using cell imaging (immunohistochemistry) and changes in gene activation (transcriptomics). These experiments lay the groundwork for a new therapy that can directly control glial activity in the central nervous system.

Noninvasive electrical stimulation is used clinically for motor rehabilitation following spinal cord injury, and as adjunct therapy across a variety of pain conditions such as peripheral neuropathy, complex regional pain syndrome, and migraine. Similar implantable devices are used to drive somatosensory feedback for upper limb prostheses that improve limb function and reduce phantom limb pain in amputees.

Effective stimulation of motor and sensory fibres using any of these devices is based on a core assumption that neural responses will follow each stimulus pulse in a ~1:1 fashion. We have evidence suggesting that this assumption is flawed, and that both motor and sensory neurons consistently fail to follow stimulation patterns at the frequencies commonly used in commercially available devices (~30-200 pulses per second).

This project aims to develop better methods to activate peripheral nerves that can overcome these limitations using in-vivo human and rat electrophysiology (teased-fibre, microneurography, and electromyography), computational modelling of healthy and injured nerves, and the development of new technologies that will dramatically improve the effectiveness of functional electrical stimulation.