Researchers have developed a new drug delivery strategy that is able to block pain within the nerve cells versus on the surface of the nerve cell. They believe this could be an important development of a treatment for both chronic and acute pain.
The research was published today in the journal Science Translational Medicine and shows how a target protein that has been known to be associated with both chronic and acute pain, works within the nerve cell. The protein is called the NK-1 receptor, which is the receptor of the neuropeptide substance P. This substance mediates pain transmission, and has been the target of many drug development attempts focused on inhibiting this receptor. The efficacy of these treatments have been limited due to the drugs targeting the surface of the nerve cell. This new research shows how a target protein works inside the nerve cell, instead.
The research was conducted by Dr. Michelle Halls and Dr. Meritxell Canals from the Monash Institute of Pharmaceutical Sciences (MIPS) and the ARC Centre for Excellence in Bio-Nano Science (CBNS) at Monash University, and with Professor Nigel Bunnett, previously at Monash and now at Columbia University in the US, and Professor Chris Porter from MIPS and CBNS.
The team has learned that the NK-1 receptor controls pain once it is inside the cell - so drugs that merely block it when it is on the surface of the cell do very little. Instead, this new research shows that, in animal models, if the NK-1 receptor is blocked once it enters the nerve cell, it is possible to suppress pain more effectively.
Dr. Halls said that the new strategy of “targeting receptors inside the cell represents a new frontier in drug delivery and a novel therapeutic strategy for dealing with pain.”
Working with a multidisciplinary team of cell biologists, pharmacologists, physiologists and drug delivery experts, the researchers developed drugs that specifically target NK-1 receptors within the nerve cell. Animal studies showed that using the drugs - which have an engineered lipid attachment that targets the drug to the NK-1 receptor inside the cell, could block pain for extended periods in several animal models.
“This is a proof-of-concept study that shows that we can re-engineer current pain drugs and make them more effective. The challenge is now to translate the technology into human clinical trials. This is a complex and challenging path - but the ultimate benefits to patients with nerve pain are potentially highly significant,” Dr. Canals said.