By Pat Anson, Editor

Drugs that selectively target the melatonin MT2 receptor in the brain could be used to develop a new class of pain medication to treat patients with neuropathy, according to an international team of scientists.

Neuropathic pain is characterized by tingling pain that develops as result of nerve damage caused by conditions such as shingles, diabetes, amputation, inflammation, and cancer. About 8% of adults worldwide suffer from neuropathy. Many drugs used to treat neuropathic pain, such as Neurontin and Lyrica, often don’t work or have unpleasant side effects.

"There are very limited treatments available for neuropathic pain, and a lot of patients use opioids," said Dr. Gabriella Gobbi, an associate professor in the Department of Psychiatry at McGill University in Montreal.  "In the long term, these (opioids) can lead to addiction and severe side effects, including dependence and tolerance, opioid-induced hyperalgesia , and risk of death. For these reasons, identifying novel analgesics is of keen interest in the medical field today."

Melatonin, a hormone present in mammals and some plants, acts on the brain by activating two receptors called "MT1" and "MT2" that are responsible for regulating sleep, depression and anxiety.  Melatonin is sold over-the-counter as a sleep aid and in the treatment of sleep disorders such as jet lag and insomnia. However, there have been few long-term clinical studies on the use of melatonin in humans.

In experiments on animals, Gobbi and her colleagues demonstrated that UCM924, a melatonin MT2 receptor drug, can relieve chronic pain. They also identified the drug's mechanism of action in the brain. UCM924 activates MT2 receptors in the periaqueductal grey area of the brain, switching off the neurons that trigger pain and switching on the ones that “turn off” pain.

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

In the course of their work to investigate the efficacy of MT2 receptor drugs, the researchers discovered that UCM924 also soothes neuropathic pain at lower doses. This suggests the 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.

Over half of patients with neuropathy 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 novel drugs.

Scientists in Mexico and Italy also contributed to the study, which are reported in the journal PAIN.