Israeli scientists find unique treatment for chronic pain
Treatment would focus on limiting the ability of importin alpha-3 to carry pain signals to prevent and treat chronic pain.
By AARON REICHLower back pain 370(photo credit: Wikimedia Commons)
A new study from the Weizmann Institute of Science has found a unique approach to treating chronic pain by targeting pain gateways.Chronic pain is a serious affliction for many people, with approximately 25% of the global population suffering from it at some point in their lives. There are many potential sources for chronic pain, but if often does not show any clear cause. These pains can be anywhere on the body, and could linger for years if not for an entire lifetime.However, while chronic pain could be caused by any number of injuries or medical conditions, the pain itself starts in one place: sensory neurons. These nerve cells are responsible for transmitting information about external stimuli from the skin to the body's central nervous system. In other words, it is responsible for telling the body that it's in pain. But it is possible for these neurons to, essentially, glitch, sending the nervous system continuous pain messages rather than brief, acute pain messages. These glitches can be caused by a number of potential factors, such as disease, chronic injury or damage to the neurons themselves.However, the new study, published on Thursday in the academic journal Science, has found a way to regulate the messages sensory neurons transmit. This is done with the help of importins, molecules found in every cell that act as a sort of messaging conduit. Different importins carry different messages, but Dr. Mike Fainzilber, of the Weizmann Institute's Biomolecular Sciences Department, has identified several key importins that relay pain signals.In order to investigate the involvement of importins in the chronic neuropathic pain, researchers led by the Institute's Dr. Letizia Marvaldi screened the behavior of certain importin movements. As a result of this screening, a specific importin was found to be the one involved in controlling the pathways for transmitting pain signals: Importin alpha-3.From there, the researchers sought to find additional variables in the process. This brought them to c-Fos, a protein the importin alpha-3 carries. It is also a molecule that lowers or raises expression, and studies on mice showed that it accumulates in cells during chronic pain.Using specialized viruses, the team tested on mice, reducing or disabling importin alpha-3 or c-Fos in the nerve cells. As a result, the mice showed reduced responses to chronic pain situations.Further research developed on this, clarifying that importin alpha-3 is critical in late and chronic pain, while c-Fos is involved in earlier pain as well, though it enters cells by other means then. In other words, blocking importin alpha-3 activity could be used to prevent or treat lasting chronic pain.After reviewing these findings, the team tookt his a step further to understand possible clinical application. After utilizing a specialized database, the Connectivity Map (CMap) from the Broad Institute in Massachusetts, the team identified 30 existing drugs that could target the importin alpha-3-c-Fos pathway, two thirds of which were not associated with pain relief. Testing two (one cardiotonic drug and one antibiotic) of these on mice, the researchers observed a relief of pain symptoms.“The compounds we identified in this database search are a kind of fast track – proof that drugs already approved for other uses in patients can probably be repurposed to treat chronic pain,” Marvaldi said in a statement.
“Clinical trials could be conducted in the near future, as these compounds have already been shown to be safe in humans.”“We are now in a position to conduct screens for new and better drug molecules that can precisely target this chain of events in the sensory neurons,” Fainzilber explained.“Such targeted molecules might have fewer side effects and be less addictive than current treatments, and they could provide new options for reducing the burden of chronic pain.”
