Columbia scientists discover promising new treatment for chronic pain

" We believe a compound like N60 has significant potential to transform the way chronic pain is treated," is a welcome message for chronic pain sufferers and a hopeful signal that a way to help thousands of people may soon be available.

Columbia scientists tell us they may have found a new way to treat pain that doesn't lead either to tolerance or addiction, which have been controversial barriers in the treatment of chronic pain.

“If it works the way we think it can, we may be able to alleviate chronic pain in some of its most intractable forms without the risk of addiction, a problem that conveys a whole set of economic and social issues for our country and society at-large.” is what Dr. Richard Ambron, Professor of Pathology & Cell Biology at Columbia University goes on to say about something that could make a significant difference for many people.

These scientists were working to combat injury-related depression, substance abuse and suicide due to unremitting, persistent pain when they found a powerful analgesic dubbed N60 and how it can work to prevent chronic pain, yet maintain ordinary pain signals that can be helpful in signaling the body that danger is present.  .

Pain, as defined by medical science, is perceived in the brain following signals that travel along nerves in the peripheral nervous system. It is a sensation that serves as a defense mechanism for humans that scientists do not know in all of its complexities; but it is known there are several pathways by which the brain perceives different types of pain. 

The research team, began to develop N60  Dr. Ying-Ju Sung, Assistant Professor of Clinical Pathology, discovered the pathway that neurons use to inform the brain of an injury. Left uncontrolled, this pathway continues to alter the electrical properties of the neuron, which results in chronic pain.   What has been needed is something to switch that off.  The Columbia team found that a specific protein in the pathway that has to be deactivated  called PKG.   It is important to be able to virtually deactivate that switch because the brain continues to receive signals that are perceived as pain, even after an injury has healed.

Sung and Ambron recognize that PKG would be an excellent target for drug development.   What is especially unique, in addition to removing those concerns about addiction and other barriers, is that PKG is specific for biochemical signaling involved with chronic pain, shutting off PKG will not prevent a patient from feeling fresh injuries. It also operates in the peripheral nervous system, rather than the central nervous system. This means that a drug that blocks PKG does not have to cross the blood-brain barrier, which has been a challenge before in the development of a drug that can alleviate pain.

“The only drugs that work consistently on chronic pain are opiates and anti-depressants,” said Ambron. “A significant problem with opiates is that extended use often leads to addiction.”

“Everyone is looking for a solution that is not addictive,” Sung added. “There’s increasing concern, from clinicians, patients, and regulatory agencies, with drugs that act on the central nervous system where addiction can develop.”

Once they understood the function of PKG, the team went on to discover N60, a compound tht would block PKG from sending signals to the brain. 

“We found in PKG a well-defined target that has been implicated in several types of pain that are particularly refractory to treatment,” Ambron said. “Now, we have an excellent inhibitor of the target which imparts no evident toxic or behavioral side effects and which also alleviates chronic pain in animal models of nerve injury and inflammation. N60 is non-addictive and non-sedative, and a single dose attenuates pain for at least 24 hours.”

According to researchers, N60 may help military personnel at high risk from chronic pain resulting from injuries received during combat.  

“We’ve got the drug, we’re confident in its efficacy, and we are actively looking for investors and experienced partners to help us put this through clinical testing,” explains Jerry Kokoshka, a representative from Columbia Technology Ventures, the university office that oversees commercialization of novel technologies. “Anyone who has ever experienced the suffering of chronic pain, personally or through a family member or friend, knows the intense frustration and emotional burden of this problem."