Hiroshima University researchers have identified a specific molecule that maintains pain after a nerve injury and have been able to block it in lab animals. This discovery may reveal a promising therapeutic strategy for treating neuropathic pain.

Lab animals with an injury to their sciatic nerve showed less pain after multiple injections of a medication that blocks the activity of a molecule called high-mobility group box-1 (HMGB1). The team also discovered that a single dose of a substance to block the activity of a different molecule, called matrix metalloprotease-9 (MMP-9), could also alleviate pain from the injury. The chemical pathways these substances use to inhibit HMGB1 or MMP-9 are different from common pain releivers, like opioids or acetaminophen. Therefore, the potential for addiction or negative side-effects may be reduced.

The results reveal that the substance to block HMGB1, called anti-HMGB1, has the downstream effect of preventing the increase of MMP-9 that would normally be expected when HMGB1 increases. Therefore, an inhibitor of MMP-9 may be a more direct route to produce the same effect. This is the first study to link HMGB1 and MMP-9 together in the cellular process of maintaining pain. These researchers, led by Professor Yoshihiro Nakata, PhD, at Hiroshima Umiversity's Institute of Biomedical and Health Sciences began their investigation of sciatic nerve pain as part of their long-term studies of the central nervous system.

Professor Nakata's team demonstrates a pain-relieving effect from injecting anti-HMGB1 into the hip in the slightly broader area around the nerve, called a perineural injection, avoiding the complications of other injectiom methods. A localized injection also avoids the potential side-effects of delivering the medication through larger body systems, like a pill into the digetsive system or an injection into the blood. Blocking HMGB1 lessened pain with no negative impact or healing. Selectively blocking MMP-9 also relieved pain with no obvious changes to the activity of other molecules responding to the injury.

It is surmised these results show promise for relieving nerve pain wit a chemically specific approach that is convenient for patients.

Source: ScienceDaily, 29 February 2016 from Hiroshima University.