Research neurobiologists and anesthesiologists have created opioid receptors that respond to light in the same way as the binding sites in the brain respond to painkilling drugs.

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Certain painkilling drugs bind to opioid receptors in the brain and spinal cord.

The laboratory findings in test tubes and animals have been published in the journal Neuron.

The researchers did the experiments for the Washington University School of Medicine in St. Louis, taking light-sensitive rhodopsin – the protein in the eye’s retina that responds to light – to modify key parts of opioid receptors.

These test tube-produced receptors were then injected into the brains of mice, and the experiment showed that their behavior could be manipulated by light. An apparent dopamine reward response, instead of by opioid drugs, was stimulated by light.

The neuroscientists say the “line of discovery” raises the hope of developing ways of using light to relieve pain, although more likely first is that revelations follow this work on how best to activate and deactivate opioid receptor pathways in brain cells.

Michael Bruchas, PhD, the study’s principal investigator and an assistant professor of anesthesiology and of neurobiology, explains that using light is a simpler way of investigating opioid receptors than deploying analgesic drugs.

Gaining a greater understanding of how the receptors function within the complex array of cells and circuits in the brain and spinal cord could in turn lead to more effective, safer painkillers.

First author Edward Siuda, a graduate student in Dr. Bruchas’ laboratory, confirmed:

“It’s conceivable that with much more research we could develop ways to use light to relieve pain without a patient needing to take a painkilling drug with side effects.”

The steps toward such a future may now be easier. Specific chemical pathways are activated in the brain and spinal cord when an opioid receptor is exposed to a painkilling drug. When the researchers shone light on the rhodopsin-added receptors – specifically, the protein was added to the mu-opioid receptor – these same pathways were triggered.

Dr. Bruchas explains the complexities that may now be simplified: “It’s been difficult to determine exactly how opioid receptors work because they have multiple functions in the body. These receptors interact with painkilling drugs called opiates, but they also are involved in breathing, are found in the gastrointestinal tract and play a role in the reward response.”

Now, however, the opioid receptors have been limited to performing a single task at a time, and the researchers have found this can be almost as easy as turning on a light!

Compare this with decades of opioid studies in which reward responses in mice and rats have been observed when they press a lever to receive a drug dose – morphine, for example – that activates opioid receptors and dopamine release. The animals, stimulated in the reward centers of their brains, then keep going back for more.

A similar reward sensation has now been delivered with light by the researchers. Collaborators with Dr. Bruchas and Mr. Siuda included co-first author Bryan Copits, PhD, a postdoctoral researcher in the laboratory of professor of anesthesiology Robert Gereau, PhD.

The mice in their study were put into a black, opaque, enclosed chamber, one part of which had a laser to trigger fiber-optic implants. The implanted animals that had been injected with the dopamine-triggering light-sensitive receptors spent more time in the lit part of the box.

When they left that part of the chamber, the rewarding stimulation no longer persisted, so they soon returned for more of the LED light stimulation.

The researchers were able to vary the animals’ response depending on the amount and type of light emitted – slightly different effects were produced with:

  • Different color
  • Longer and shorter exposure
  • Constant or pulsing light.

Dr. Bruchas sums up:

“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.”

Advancement on this early research development toward reducing the abuse potential and side effects of opioid drugs to relieve pain remains theoretical, but Mr. Siuda says it “someday may be possible to activate, or deactivate, nerve cells without affecting any of the other receptors that painkilling drugs trigger, although achieving that goal will be difficult.”

Meanwhile, research into improving present drugs such as OxyContin continues. In April, for example, we reported findings of a drop in abuse and overdose after opioids were made crush-resistant.