Mice received injections of drugs that specifically block the activity of two different molecules. Blocking those molecules reduced pain symptoms coming from nearby nerves. Credit: Hiroshima University
A specific molecule involved in maintaining pain after a nerve injury has been identified and blocked in mice by Hiroshima University researchers. These results reveal a promising therapeutic strategy for treating neuropathic pain. Mice with an injury to their sciatic nerve showed less pain after multiple injections of a drug that blocks the activity of a molecule called high-mobility group box-1 (HMGB1). Researchers also discovered 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.
The chemical pathways that these drugs use to inhibit HMGB1 or MMP-9 are different from common pain relievers, like opioids (Morphine) or acetaminophen (Tylenol). Therefore, the potential for addiction or negative side-effects may be reduced.
The results reveal that 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. Therefore, an inhibitor of MMP-9 may be a more direct route to produce the same effect.
Sciatic nerve pain, or sciatica, causes pain in the lower back, buttocks, or back of the leg and is often caused by a herniated disc in the spine or a pinched nerve. Similar pain can occur in different nerves in patients with cancer or diabetic neuropathy. Previous studies by other research groups have injected anti-HMGB1 underneath the protective membranes surrounding the nerve. This method, called an intrathecal injection, is more complicated for doctors to perform and has more potential risks.
Prof. 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 injection methods. A localized 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.
http://www.eurekalert.org/pub_releases/2016-02/hu-ntf022816.php
Recent Comments