Researchers have developed a new way to treat chronic pain which has been tested in mice. With a compound designed and developed by the researchers themselves, they can achieve complete pain relief.

Between seven and ten percent of the world's population suffers from chronic pain originating from nerves that have been damaged. A disease that can be severely debilitating. Now, researchers from have found a new way to treat the pain.

The treatment has been tested in mice, and the new results have been published in the scientific journal EMBO Molecular Medicine. For more than a decade, the researchers have been working to design, develop and test a drug that shall provide complete pain relief.

"We have developed a new way to treat chronic pain. It is a targeted treatment. That is, it does not affect the general neuronal signalling, but only affects the nerve changes that are caused by the disease," says co-author.

Chronic pain can occur, among other things, after surgery, in people with diabetes, after a blood clot and after an amputation in the form of phantom pain.

The compound developed by the researchers is a so-called peptide named Tat-P4-(C5)2. The peptide is targeted and only affects the nerve changes that pose a problem and cause the pain.

Tat‐P₄‐(C5)₂ is a cell‐permeable, high‐affinity (~2 nM) peptide inhibitor of the PDZ domain protein PICK1 to interfere with increased AMPAR expression. The affinity is obtained partly from the Tat peptide and partly from the bivalency of the PDZ motif, engaging PDZ domains from two separate PICK1 dimers to form a tetrameric complex.

Bivalent Tat‐P₄‐(C5)₂ disrupts PICK1 interaction with membrane proteins on supported cell membrane sheets and reduce the interaction of AMPARs with PICK1 and AMPA‐receptor surface expression in vivo. Moreover, Tat‐P₄‐(C5)₂ administration reduces spinal cord transmission and alleviates mechanical hyperalgesia in the spared nerve injury model of neuropathic pain.

In a previous study, the researchers have shown in an animal model that use of the peptide can also reduce addiction. Therefore, the researchers hope that the compound may potentially help pain patients who have become addicted to, for example, opioid pain relievers in particular.

"The compound works very efficiently, and we do not see any side effects. We can administer this peptide and obtain complete pain relief in the mouse model we have used, without the lethargic effect that characterises existing pain-relieving drugs," says the author:

"Now, our next step is to work towards testing the treatment on people. The goal, for us, is to develop a drug, therefore the plan is to establish a biotech company as soon as possible so we can focus on this."

https://healthsciences.ku.dk/newsfaculty-news/2020/04/researchers-are-developing-potential-treatment-for-chronic-pain/

https://www.embopress.org/doi/full/10.15252/emmm.201911248

http://sciencemission.com/site/index.php?page=news&type=view&id=publications%2Fa-high-affinity&filter=22