Researchers have found a new way to block a root cause of pain. The key is a naturally occurring protein called apolipoprotein A-I binding protein (AIBP). AIBP binds to toll-like receptor 4 (TLR4), a protein that sits on the surface of cells like an antenna, searching for signs of infection or tissue damage. The researchers found that treating mice with a single spinal injection of AIBP and thus switching TLR4 "off" prevented and reversed inflammation and cellular events associated with pain processing. The study was published in Cell Reports.
Opioids and most other pain medications simply dampen a person's perception of pain. But the source of the pain is still there. At the same time, opioids also impart a feeling of pleasure, which leads to their misuse and addiction.
By inhibiting the TLR4 receptor with AIBP, is that it modifies the pain processing systems themselves. So, if you think of neuropathic pain as a disease, then we see this as truly disease-modifying. They are blocking the underlying mechanism that causes pain, not just masking the symptoms.
Historically, researchers thought inflammation and nerve injury were separate events. But a few years ago, he, co-author Maripat Corr, MD, and collaborators found that sometimes inflammation can transition to chronic pain with all the hallmarks of nerve injury, a cellular event that involves TLR4. My specialty is atherosclerosis, the underlying cause of heart attack and stroke, and we had been studying AIBP as a means to treat that condition. But they were also surprised to find that at the same time AIBP prevented and reversed chronic pain states.
In laboratory tests, the researchers discovered that AIBP inhibited TLR4 by removing cholesterol from lipid rafts cholesterol-rich areas of a cell's membrane that help control how cells communicate with each other and their environments. The injections also reduced TLR4 activation, microglial activation, and inflammation in the spinal cord.
After chemotherapy, humans, and animals often develop persistent states of pain in response to even the lightest touch. In this study, mice that received chemotherapy reacted to the lightest touch. But a single intrathecal injection of AIBP completely reversed the chemotherapy-induced pain state, and the mice were able to endure normal levels of mechanical stimulation. This pain-relieving effect lasted for two months, and the AIBP injection did not affect motor functions.
They are working on ways to deliver AIBP systemically, but if it comes down to a choice between living with chronic pain or getting a spinal injection once every few months, we think most people would take the injection. If each of those patients takes an average 100 milligrams of morphine or its equivalent per day for one year, an estimated morphine burden would be approximately 24,000 kilograms per year, and that's just for patients with cancer.
They are not saying they should not use opiates to treat chronic pain or in particular cancer pain that would be a tragedy. But it would also be a greater tragedy if we didn't support work to find a substitute for systemic opiates, if for no other reason to reduce its presence in our society.