An old antipsychotic offers a new way to treat chronic pain

A decades-old antipsychotic drug helped identify a new pathway to treat chronic pain — as well as an unusual link to lung cancer.

Fluphenazine, previously used to treat schizophrenia, was one of 1,000 FDA-approved drugs that researchers have evaluated, hoping to find a drug that can reduce a chemical released by nerve cells (called BH4) linked to chronic pain. .

“We found that fluphenazine blocks the BH4 pathway in injured nerves,” project leader Shane Cronin, a scientist at the Austrian Academy of Sciences’ Institute of Molecular Biotechnology (IMBA), said in a statement. He said.

A decades-old antipsychotic drug helped identify a new pathway to treat chronic pain — as well as an unusual link to lung cancer.

The study was conducted on mice and published in Translational Medicine SciencesIt could help reveal new ways to ease the suffering of millions of people suffering from chronic pain.

Current chronic pain therapies are often ineffective, said co-author Clifford Wolf, professor of neurology and neuroscience at Harvard Medical School and director of the FM Kirby Neurobiology Center at Boston Children’s Hospital.

Moreover, effective painkillers such as opiates, if used inappropriately, can lead to severe addiction. It is therefore essential to find and develop new and reused medicines to treat chronic pain.”

Teams around the world are racing to make it happen. Investigation Genetic therapies, narcotics, electrical implants, as well as re-examination decades old belief On treating pain and transforming into Wide range of natural toxins for new treatments.

Previous research by Wolff’s team identified BH4 blocking as a potential treatment for chronic pain.

“BH4 concentrations correlate very well with pain intensity,” said Cronin, a former postdoctoral researcher at Wolff. “So we naturally thought this was a great avenue for targeting.”

Researchers examined already approved drugs to determine which ones have previously unknown analgesic properties related to BH4. In doing so, they were able to link the previously known, but poorly understood, analgesic effects of other compounds, such as capsaicin – the compound that makes chili peppers – to the BH4 pathway.

And they discovered at least one ancient property that they could repurpose.

The researchers screened already approved drugs to determine which ones had previously unknown analgesic properties, and they beat up fluphenazine.

They tested the ability of fluphenazine to lower BH4 in mice, determining that the dose of the painkiller is comparable to the minimum dose range used to treat schizophrenia.

Interestingly, the team also found a direct relationship between cancer and chronic pain. EGFR/KRAS signaling, a pathway implicated in aggressive lung cancer, appears to share a pathway with BH4. When an enzyme in the BH4 pathway was knocked down, mice that were engineered to model KRAS-derived lung cancer developed fewer tumors and lived longer.

“The same stimuli that drive tumor growth also appear to be involved in paving the way to chronic pain, which cancer patients often experience,” said IMBA’s Joseph Benninger.

Discovering this interaction could lead not only to cancer treatments, but to better management of the chronic pain of cancer patients.

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