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Japanese researchers block molecule that maintains sciatic nerve pain

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Researchers in Japan have identified and blocked a specific molecule involved in maintaining pain after a sciatic nerve injury.

The findings point to a promising therapeutic strategy for treating neuropathic pain, Hiroshima University said last week.

During the study, a research team led by Professor Yoshihiro Nakata at Hiroshima University´s Institute of Biomedical and Health Sciences administered a drug to mice with an injury to their sciatic nerve. They found that multiple injections of a drug that blocks the activity of a molecule called high-mobility group box-1 (HMGB1) resulted in a significant decrease in pain.

The study also showed that a single dose of a drug to block the activity of a different molecule, called matrix metalloprotease-9 (MMP-9), could also alleviate pain from the injury.

According to findings published in the Journal of Neurochemistry, the drug 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. As such, 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, the researchers claimed.

Prof. Nakata´s team demonstrated 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 injection methods. A localised injection also avoids the potential side-effects of delivering the drug through larger body systems, like a pill into the digestive system or an injection into the blood.

Blocking HMGB1 lessened pain with no negative impact on healing. Selectively blocking MMP-9 also relieved pain with no obvious changes to the activity of other molecules responding to the injury, the researchers said.

The university noted that the chemical pathways that these drugs use to inhibit HMGB1 or MMP-9 are different from common pain relievers, like opioids or acetaminophen. This means that there may be less risk of addiction or negative side-effects.

In humans, sciatic nerve pain, or sciatica, causes lower back pain that radiates from the nerves in the back to one or both legs. It is caused by irritation to, or damage of, the sciatic nerve, which runs from the spine all the way down to the feet.