US – A research group at Duke University has found a prospective innovative class of small-molecule drugs that concurrently inhibit 2 desired targets in the pain therapy.

These preliminary findings, published in the journal Scientific Reports, may bring about developing an innovative medicine to deal with conditions such as skin discomfort together with itchiness, migraines, jaw pain, as well as abdominal pain coming from the colon and pancreas.

Millions of individuals are afflicted by chronic pain in the US, based on a study from the Institute of Medicine, and innovative drugs are desperately necessary.

Wolfgang Liedtke, M.D., Ph.D., a professor of neurology, anesthesiology and neurobiology at Duke University School of Medicine, said that they happy with what is the beginning of a promising story and they hope to succeed in developing these molecules for clinical use in animals or humans.

In this research study, they initially targeted to produce far better blockers of TRPV4, a compound their preceding study had revealed sends skin irritation elicited by too much sun, plus agonizing sensations eminating from the head and face. Liedtke and his Duke collaborator Farshid Guilak used a prototype TRPV4 blocker in a 2009 study and then set out to develop more potent versions.

Relative to the prototype, one of the novel drugs, known as “16-8,” performed ten times better in cells having active TRPV4 that are vital osteoarthritis development. Additionally, it proved helpful in a different cell type related to nerve cell damage, stroke not to mention epilepsy.

However to their amazement, when evaluating the specificity of 16-8, the researchers found that it additionally hindered TRPA1, which is an appealing goal in pain not to mention itch research.

Both TRPV4 and TRPA1 are members of the family of TRP ion channels. They work in sensory nerve cells to directly sense painful stimuli. Other research teams are now focusing on these channels in clinical trials for pain alleviation.

In this research, the drug 16-8 also suppressed discomfort in living animals, such as stomach pains in mice having pancreas inflammation. Pancreatitis is exceedingly distressing and hard to treat while new cases are  rising throughout the world.

Liedtke foresees prospects for the 16-8 drug in treating osteoarthritis along with varieties of joint pain and in addition face, head, and jaw pain. Generally, it could likewise treat pains exuding from internal organs or caused by nerve cell damage.

The team’s preclinical work will concentrate on learning the compound’s prospective utilization in such conditions and understanding further regarding precisely how it functions. Furthermore they aspire to investigate topical applications to mucous membranes found all over the skin and body.

Article citation:

” Small molecule dual-inhibitors of TRPV4 and TRPA1 for attenuation of inflammation and pain,” Patrick Kanju, Yong Chen, Whasil Lee, Michele Yeo, Suk Hee Lee, Joelle Romac, Rafiq Shahid, Ping Fan, David M. Gooden, Sidney A. Simon, Ivan Spasojevic, Robert A. Mook, Rodger A. Liddle, Farshid Guilak and Wolfgang B. Liedtke. Scientific Reports, June 1, 2016. DOI: 10.1038/srep26894