Marino and co-workers studied the cybernetic control system that regulated the metabolism of joint cartilage, aiming to understand why the system sometimes destroyed  the cartilage, causing osteoarthritic pain. They found that cells in the synovial tissue which lined the inside of joints were electromagnetically synchronized by means of  gap junctions, thereby permitting intercellular transfer of information regarding control of the secretion of enzymes that degraded cartilage.

They showed that excessive enzyme secretion by synovial cells that is characteristic of osteoarthritis could be reduced by blocking entry of calcium ions into the cells using verapamil, which altered cell synchronization, resulting in reduced enzyme production.

In clinical studies using verapamil to treat osteoarthritic pain, Marino and co-workers found that a single verapamil injection into the knees of patients with advanced osteoarthritis significantly reduced joint pain for up to six months.  The safety and efficacy of verapamil for treating osteoarthritic pain was further tested in a multi-center clinical trial approved by the Food and Drug Administration.