Using light to activate the brain’s opioid receptors

Better than morphine? Using light to activate the brain’s opioid receptors


The hope is that eventually these findings will lead to new and improved ways of relieving pain with light. In the meantime, it should be possible to use these tools to study the best ways to activate and deactivate opioid receptors in brain cells.

By combining rhodopsin, the light-sensing protein from the retina with crucial parts of the mu opioid receptor, they created a novel protein known as opto-MOR. When stimulated with light these receptors promote exactly the same cellular pathways as opiates like morphine.

For a long time, opioid drugs have been the best treatment for severe pain, despite their potential for abuse. The main issue with using opiates is that they have multiple functions in the brain. They are involved in breathing, are found in the gastrointestinal tract and play a role in the reward response.

Additionally, because they are usually taken systemically, receptors for each of these areas or functions are activated, leading to unwanted side effects. Light can be directed just to the cells associated with the source of pain and using optogenetic tools, the light-sensitive receptors can also be selectively expressed on certain cell types.

The researchers from Washington University School of Medicine in St Louis showed that when the modified receptors were expressed in cells they produced the same chemicals as a standard opioid receptor does when activated.

The team then implanted a light-emitting diode (LED) device the size of a human hair into mice in a brain region linked to the reward response. They also injected the opto-MORs into the same part of the brain. Neurons in this area release chemicals such as dopamine that create feelings of euphoria.

The mice were placed in an enclosed chamber. In part of the chamber, the device stimulated the release of dopamine through the altered mu opioid receptors. If the animals left this area the light turned off. When left to move around the chamber freely, mice that left the part of the chamber where the light was turned on would quickly return to receive more stimulation.

Dr Michael R Bruchas, principal investigator in this study, said: “By activating the receptors with light, we are presumably causing the brain to release more dopamine. Rather than a drug such as morphine activating an opioid receptor, the light provides the reward.”

The animal’s response to the LED could be modulated by altering the length of exposure, using pulsed or constant light or changing the colour of the light.

Opioid receptors that can be mediated with light have the potential to be a lot safer than those activated with commonly used opiates like morphine, Vicodin or OxyContin. The ability to tightly control pain relief in time and space should lead to fewer side effects and addictive behaviour. However, there are a number of difficult challenges to overcome before this is possible in human patients.

Paper reference:

Siuda ER, Copits BA, Schmidt MJ, Baird MA, Al-Hasani R, Planer WJ, Funderburk SC, McCall JG, Gereau RW, Bruchas MR Spatiotemporal control of opioid signalling and behaviour Neuron 86:4 923-935 (2015) doi: 10.1016/j.neuron.2015.03.066

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