Could melatonin drug treat neuropathic pain?

"There are very limited treatments available for neuropathic pain, and a lot of patients use opioids," says Gabriella Gobbi. "In the long term, these can lead to addiction and severe side effects." (Credit: iStockphoto)

Drugs that target a specific melatonin receptor appear to relieve chronic pain that results from nerve damage.

This condition, known as neuropathic pain, is often severe and can be permanent. It develops after nerve damage from conditions such as shingles, injury, amputation, autoimmune inflammation, and cancer.

Melatonin, a neurohormone present in mammals, acts on the brain by activating two receptors called MT1 and MT2. Those receptors are responsible for regulating several functions, including sleep, depression, anxiety, and circadian rhythms.

A team led by Gabriella Gobbi, associate professor of psychiatry at McGill University, demonstrated that a drug called UCM924, which targets the MT2 receptors, relieves chronic pain in animal models. The team also identified the drug’s mechanism in the brain.

The drug is able to switch off the neurons that trigger pain and switch on the ones that turn off pain by activating the MT2 receptors in the periaqueductal grey (a brain area controlling pain). The findings are reported in the February issue of the journal PAIN.

“There are very limited treatments available for neuropathic pain, and a lot of patients use opioids,” says Gobbi. “In the long term, these can lead to addiction and severe side effects, including dependence and tolerance, opioid-induced hyperalgesia (the pain becomes even worse), and risk of death.

“For these reasons, identifying novel analgesics is of keen interest in the medical field today.”

Why melatonin alone is not enough

Previous studies have shown that over-the-counter melatonin has very limited effect. Gobbi and her team demonstrated that this is because exogenous melatonin activates both MT1 and MT2 receptors, which have conflicting and opposite effects.


In the course of their work to investigate the efficacy of MT2 receptor drugs for insomnia, the researchers discovered that UCM924 also soothes neuropathic pain at lower doses. This suggests that these drugs could offer relief both to people who suffer from pain during the day, using low doses, and from insomnia at night, using higher doses.

At least 50 to 70 percent of patients with neuropathic pain conditions complain of significant sleep disturbance, and this new study unveils how the mechanisms of pain and sleep are closely related.

The research team is now looking for partners interested in pursuing clinical development and eventual commercialization of these new drugs.

Scientists from University Veracruzana (Mexico), the Second University of Naples (Italy), the Scuola Superiore Sant’Anna (Italy), the University of Milan (Italy), University Carlo Bo (Italy), and Cinvestav-Sede Sur (Mexico) also contributed to the study.

The research was supported by the Canadian Institutes of Health Research, Le Fonds de recherche du Québec – Santé, the Canadian Foundation for Innovation, and the Ministère de l’Économie, de l’Innovation et des Exportations.

Source: McGill University