Optogenetics may someday provide doctors with a noninvasive, highly focused way to treat chronic pain. By making the cells responsible for pain transmission sensitive to light, the technique may be able to target, desensitize and reduce bioelectric activity in these cells.
To demonstrate the potential role of optogenetics in pain management, researchers at McGill University bred a transgenic mouse model with a light-sensitive trait in the Nav1.8+ nociceptors, i.e., the peripheral neurons that are known to transmit pain. The terminals of the peripheral nociceptors were silenced optogenetically with a high degree of spatiotemporal precision, leading to the alleviation of inflammatory and neuropathic pain.
An optogenetic technique is being explored for pain relief. Courtesy of McGill University.
The nociceptors of the genetically modified mouse expressed proteins called opsins, which react to light. When the nociceptors were exposed to yellow light, the opsins moved ions across the membrane, reducing the level of bioelectric activity of the cells. The yellow light stimulation reliably blocked electrically induced action potentials in dorsal root ganglion (DRG) neurons in the mouse, effectively shutting off the nociceptors and decreasing the mouse's sensitivity to touch and heat in the hind paw. Basal mechanical sensitivity was not affected by the optical stimulation.
In this experiment, the activity of pain-signaling neurons was reduced in a localized part of the mouse's body, and the duration of the effect could easily be controlled by the amount of time the light was applied. An approach such as the one taken by the McGill team could be applied to functionally investigate other subsets of sensory neurons with high temporal precision.
"The opsins we added to the neurons ... sense yellow light," said professor Philippe Séguéla. "When we transfer these to neurons, we can control their responses simply by illuminating the skin with innocuous yellow light.”
The precision of this technique underlines potential advantages for use in humans. Light therapy based on optogenetics would have the advantage of providing on-demand analgesia to patients who could control their pain by shining light on the sensitive part of the body.
Opiates are the most commonly used treatment for chronic pain today, but they are often used systemically and not directed to the specific region of the body affected by the pain. The duration of the opiate effects can be estimated but without the same precision as a beam of light.
The potential for safe genetic delivery of inhibitory opsins to alleviate pain may prove useful for clinical applications. However, further advances in neuroscience are necessary to apply this method of pain relief to humans.
Séguéla says one possible way to make human neurons photosensitive would be through the use of a harmless virus that could temporarily deliver opsins to certain neurons without causing side effects.
"Chronic pain is an increasingly big problem clinically and for many years we've relied only on opiates," said Séguéla. "It's hard to treat because of tolerance, making it necessary to increase dosages, which leads to serious side effects. Optogenetic therapy could be a highly effective way to relieve chronic pain while avoiding the side effects of traditional pain medication."
The research was published in eNeuro (doi: 10.1523/eneuro.0140-15.2016).
For additional information on the use of light in the control and repair of neural circuits, see Optogenetic Method Investigated for Neuron Repair, January 2016, and New Optogenetic Tool Controls Neuronal Signaling, July 2014.