Ronald Tallarida, Ph.D., and Alan Cowan, Ph.D., of Temple's School of Medicine, and Robert Raffa, Ph.D., of Temple's School of Pharmacy, conducted the study "Antinociceptive Synergy, Additivity, and Subadditivity with Combinations of Oral Glucosamine Plus Nonopioid Analgesics in Mice," which was published in the November 2003 issue of JPET.
Ibuprofen is a non-steroidal anti-inflammatory drug, or NSAID. NSAIDs, which also include aspirin, are quite effective in relieving pain. They are so effective, in fact, that pain sufferers sometimes take higher and higher doses in hope of more pain relief. High doses of NSAIDs, especially when taken over long periods of time, can cause gastrointestinal upset, such as heartburn, or even bleeding.
"Combining pain relievers into one pill can increase patient compliance, simplify prescribing, and improve efficacy without increasing side effects, or conversely, decrease side effects without losing efficacy," said Raffa.
In addition to these benefits, drug combinations can also sometimes yield a totally unexpected effect, such as the magnification of a drug's powers. "When this happens, a phenomenon known as drug synergism, it's like finding buried treasure," added Tallarida.
Glucosamine, a naturally occurring substance in the body, which is also available in synthetic form over the counter, is used to treat osteoarthritis, a painful, degenerative joint disorder. While it has been shown to prevent and repair bone and cartilage damage, researchers have yet to demonstrate that glucosamine actually blocks pain.
"We embarked on this study with several questions: Can glucosamine actually block pain? And, can glucosamine improve the pain-relieving powers of other drugs when the two are combined?" said Tallarida.
First, the researchers confirmed that glucosamine, alone, does not block pain. It's believed that any pain-relieving properties of glucosamine are a side effect of its ability to repair bone damage. Next, they combined glucosamine with a variety of NSAIDs at a variety of dosages. With several NSAIDs, including naproxen, the addition of glucosamine caused an additive effect, meaning the sum of each drug's properties. When combined with aspirin or acetaminophen, the result was subadditive, or less than the sum of each drug's properties. But when combined with ibuprofen, the researchers found pain relief was enhanced and therefore synergistic.
"The next step will be to study this drug combination in clinical trials to see whether it can enhance pain relief or offer pain relief using a lower dose of ibuprofen and therefore a lower risk of side effects," said Cowan. The researchers are also investigating other possible drug combinations for the potential relief of pain. Raffa and Tallarida played a role in the development of Ultracet, a combination of tramadol and acetominophen used in the treatment of pain. And Cowan contributed to the development of buprenorphine which, when combined with naloxone, is used in the treatment of opiate addiction.
Journal
Journal of Pharmacology and Experimental Therapeutics