Glucosamine / pain reliever

This doesn't serve this NG at all. The pharmacologist doesn't know how to talk to a patient, much
less measure the pain threshold of a mouse or rat. Below is the abstract of the article.

Antinociceptive synergy, additivity, and subadditivity with combinations of oral glucosamine plus
nonopioid analgesics in mice. Tallarida RJ - J Pharmacol Exp Ther - 01-NOV-2003; 307(2): 699-704
From NIH/NLM MEDLINE

Journal of Pharmacology and Experimental Therapeutics

Glucosamine (2-amino-2-deoxy-d-glucose) and glucosamine-containing products have been reported to
have efficacy in the treatment of various musculoskeletal disorders. Glucosamine's efficacy,
including reduction of pain, is attributed to disease-modifying properties, specifically to cartilage-
rebuilding associated with modulation of interleukin-1-induced activation of chondrocytes and to
inhibition of proinflammatory effects of the nuclear factor-kappaB pathway. However, glucosamine has
not been shown to have direct analgesic activity. We report here that commercial glucosamine (90.4%
glucosamine sulfate + 9.6% excipients) administered as the sole agent (up to 500 mg/kg p.o.) was
inactive in the mouse abdominal irritant test but that certain combinations of glucosamine with
nonopioid analgesics at the oral doses and ratios tested resulted in a synergistic (ibuprofen and
ketoprofen), additive (diclofenac, indomethacin, naproxen, and piroxicam), or subadditive (aspirin
and acetaminophen) antinociceptive interaction. In the specific case of ibuprofen, the racemate
(standard ibuprofen) produced dose-related antinociception with ED50 = 26.1 +/- 3.4 mg/kg.
Combinations containing racemic ibuprofen and glucosamine in greater than 1:1 ratio
(glucosamine/ibuprofen) were synergistic in the test (e.g., ED50 = 11.0 +/- 2.1 for the 9:1 ratio; p
< 0.01, analysis of variance). Combinations containing glucosamine and ibuprofen (2:1 and 9:1)
yielded plasma levels of ibuprofen that were no different from administration of ibuprofen alone.
The possibility that combinations containing certain fixed ratios of glucosamine and certain
nonsteroidal anti-inflammatory drugs (NSAIDs) might enhance pain relief in patients with pain or
might achieve acceptable levels of pain relief with lower doses of NSAIDs (reduced adverse effects)
is presently being pursued in clinical trials.

doe said:

New Drug Combination Might Be More Effective Pain Reliever The nutritional supplement,
glucosamine, boosts the pain relieving power of ibuprofen, according to a new study by Temple
University researchers in the Journal of Pharmacology and Experimental Therapeutics (JPET). This
new drug combination could one day allow patients to take a lower dose and get the same pain
relief with fewer unwanted side effects. 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.

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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.

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This story has been adapted from a news release issued by Temple University.

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