Targeting Small-Diameter Axons for Neuromodulation

University of Pittsburgh, Cape Western Reserve University, and Vanderbilt University researchers have developed a novel neuromodulation method to specifically target small-diameter axons (SDAs). Using infrared (IR) radiation it is possible to selectively and reversibly inhibit SDAs, leaving large-diameter axons unaffected. The ability to selectively target peripheral nerves could have many applications including the research and treatment of many diseases of the peripheral nervous system (PNS) such as chronic nausea, vomiting and pain. 

A technique has been developed to selectively inhibit activity in SDAs. This novel approach could provide treatment for diseases of the PNS.

Description

Neuromodulation, specifically electrical stimulation of the vagus nerve, has demonstrated great success in conditions like epilepsy and depression. SDAs have crucial roles in sensory, autonomic and motor systems. Examples include small-diameter unmyelinated C-fibers carrying nociceptive signals and small-diameter unmyelinated motor axons play a role in peripheral gland and other autonomic controls. At present, no neuromodulation techniques exist to selectively target SDAs and many patients with disease of the PNS are underserved. This novel IR-based approach can selectively inhibit activity in SDAs and could allow researchers to better understand the physiological role of these axons and provide clinicians with a novel treatment strategy for PNS related conditions.

Applications

• Pain
• Chronic nausea or vomiting
• Diseases of the peripheral nervous system

Advantages

Current neuromodulation methods aimed at the PNS do not selectively target SDAs. Electrical inhibition can block all neural activity while pharmaceutical approaches require systemic delivery and can lead to off-target effects.

This novel approach uses IR radiation to completely, and reversibly, block the action potential of SDAs. Unlike electrical neuromodulation, IR is particularly advantageous due to its high temporal and spatial specificity, a lack of electrical artifact or onset responses, and is insensitive to magnetic fields. IR light can selectively block SDAs leaving other axons uninhibited.

Invention Readiness

In vitro studies confirmed IR radiation (=1860 nm) can selectively and reversibly block SDA activity when applied with low radiation exposure in identified mollusk neuron axons and in the vagus nerve (a mixed nerve of small and large diameter axons) of a shrew model. Higher radiation exposure inhibited all axons. It was confirmed that temperature changes driven by IR are responsible for axon inhibition. Work is now required to ensure these temperature changes do not cause short- or long-term changes to the axon. Work is also required to optimize this technique for safe and effective levels of radiant exposure and optimal IR parameters.

IP Status

https://patents.google.com/patent/WO2018191744A1