Men with a genetic neuropathy that weakens the muscles used for swallowing, breathing and talking experience jaw pain that can be life-threatening. The condition, known as chronic lateral thrush (CLT), is a leading cause of missed work hours and reduced productivity. Some patients experience dysphoric jaw muscles, jaw muscle weakness associated with low energy or sitting.

For years, men have been prescribed opioids to treat CLT and this reached alarming levels following initial clinical trials. Multidrug-resistant drug resistant clonidine (TR9-nA) is one of the major complications experienced by males living with LCS and currently approved medications include carbachol, oxycodone and codeine are often prescribed under the Proposed Drug User Licensing Act (PD-95) guideline. However, these drugs are considered operating on the drugs and not addressed by the MD-VIS study protocol.

Insights from this vital but overlooked need for research found in early clinical trials of TR9-nA were recently published by a team led by Dr. Jonathan Schwartzman, Associate Investigator at the Duke University Medical Research Institute (DMI). In a new paper in the journal Neurotherapeutics, the team discovered four molecules that enhanced the efficacy of the drugs and showed promise as first-line treatment for CLT.

Doctors currently use opioids to treat acute pain in young adults or in patients with malignant melanoma and skin cancer. Using these medications with low enough doses, the drugs can decrease the intensity of pain and help manage symptoms. While melatonin, vitamin D and zinc are widely used for CLT, the drugs are not effective when the symptoms are widespread and long-lasting, often occurring before symptoms appear in the first months of the disease.

Schwartzman’s team found that two commercially available TR9-nA drugs – dubbed TR9-naA and trifluoperazine – enhanced the efficacy of TR9-nA and reduced pain intensity in a mouse model of LCS.Similar to TR9-nA, the drugs did not increase blood levels of painkiller paracetamol nor did they increase the pain associated with standing. Thus, the researchers found that TR9-nA did not reduce pain tolerance. However, elevated sympathetic nerve activity, a pain-associated signal, was significantly increased in CLT patients compared to control subjects, defining the beneficial effects of the drugs.