Study Reveals Promising Way to Get Pain Relief Without Adverse Effects and Addiction

A new study by an international team of researchers has shown that substances that target different receptors to those targeted by opioids produce comparable pain relief as the latter without causing addiction and other side effects.

Back Pain

These new substances work on adrenalin receptors instead of opioid receptors to provide pain relief.

“Many non-opioid receptors are involved in pain processing, but only a small number of these alternatives have as yet been validated for use in therapies,” explained Professor Peter Gmeiner, the Chair of Pharmaceutical Chemistry at Friedrich-Alexander University (FAU) Erlangen-Nurnberg who led the study.

This research was driven by the realization that some non-opioid receptors could be targeted for pain relief. Its findings, which appeared in the journal Science, are significant for the development of pain relievers that could rival opioids.

Risky pain relievers

Opiates – or opioids generally – have been among the most vital medications for a long time. They are quite helpful for relieving or managing intense pain. According to experts, the use of opioid analgesics has been on an upward curve and North America leads the way.

These substances have ironically also been a pain in terms of the adverse effects that they can have. Dizziness, nausea, and constipation are some of these effects. Opioids can also slow down breathing, with this capable of causing respiratory failure.

Addiction is another major problem that arises from using opioid drugs. Opiates, including heroin, codeine, and morphine, are very addictive. Researchers say many cases of problematic drug use in America have a link to pain relievers that contain these substances.

Thousands of people reportedly die each year from addiction or respiratory failure stemming from the use of opiates.

Scientists have, therefore, been on a quest to find safer alternatives to opiates.

“We are focusing particularly on the molecular structures of the receptors that dock onto the pharmaceutical substances,” said Gmeiner. “It is only when we understand these on the atomic level that we can develop effective and safe active substances.”

Along with his team, the professor of pharmaceutical chemistry reported in 2016 a new active substance that bonded to opioid receptors to provide morphine-like pain relief. The substance bore no chemical resemblance to opiates.

Targeting different receptors

Gmeiner and his team, which also comprised researchers from the U.S., Canada, and China, focused on the alpha 2A adrenergic receptor. This receptor is linked to the binding of adrenaline or epinephrine.

Scientists have already made pain relievers that work on this specific receptor. Examples include dexmedetomidine, brimonidine, and clonidine. These drugs, however, have their downsides. Dexmedetomidine, for instance, is a potent sedative, so it’s best for intensive care in hospitals not for regular use.

Gmeiner and his fellow researchers set out to find a compound that can turn on the alpha 2A adrenergic receptor without causing a side effect. They wanted to find substances that bind to the receptor while bearing no chemical similarity to a known drug.

The team shortlisted about 50 molecules from a virtual library of molecules that were in excess of 300 million. Two of the selected substances met the set criteria. The molecules were very selective in terms of the cellular signal pathways that they activate, unlike dexmedetomidine.

Further modification of the two molecules by the researchers produced agonists that brought about elevated levels in the brain. In animal models, this was found to successfully lower pain sensation.

“Various tests confirmed that docking on the receptor was responsible for the analgesic effect,” stated Gmeiner. “We are particularly pleased about the fact that none of the new compounds caused sedation, even at considerably higher doses than those that would be required for pain relief.”

Even though this is only basic research, the findings are promising.

Pain relief devoid of side effects and addiction is a milestone that could aid the making of non-opioid pain relievers. It is also notable that the process is not costly and the substances can be used via the oral route. The compounds may only take years to become available for general use by humans.