Researchers working toward new class of pain drugs

Chronic pain affects approximately 48 million people in the US and current medications are either largely ineffective or have serious side effects. Most prior attempts at alleviating chronic pain have focused on the ‘second order’ neurons in the spinal cord that relay pain messages to the brain. However, it is difficult to inhibit the activity of these neurons with drugs because the drugs need to overcome the blood-brain barrier.

Instead, the Columbia University Medical Center (CUMC) researchers have focused on the more accessible ‘first order’ neurons in the periphery of the body that send messages to the spinal cord.

Pain becomes chronic when the activity of first and second order neurons persists after damaged neuron heals or the tissue inflammation subsides. It has been known for years that, for chronic pain to persist, a master switch must be turned on inside the peripheral neurons, although, until now, the identity of this switch remained a mystery. CUMC department of anatomy and cell biology researchers Dr Richard Ambron, professor of cell biology, and Dr Ying-Ju Sung, assistant professor, have now discovered that the switch is an enzyme called protein kinase G (PKG).

The researchers found that, upon injury or inflammation, the PKG is turned on and activated. Once activated, these molecules set off other processes that generate the pain messages. As long as the PKG remains on, the pain persists. Conversely, turning the PKG off relieves the pain, making PKG an excellent target for therapy.

“We’re very optimistic that this discovery and our continued research will ultimately lead to a novel approach to pain relief for the millions suffering from chronic pain,” said Dr Ambron.

Dr Ambron and Dr Sung have applied for a patent for the pathway that turns on the PKG, as well as several molecules that inhibit it.