FAQ Pain Relief
Definitions:

Cartilage is the tough elastic tissue found in the
nose, throat, ear and joints. It is like a cushion at the ends of the bones.
The cartilage between joints acts as a shock absorber, protecting the bones
and tissues from the impact created during walking and other bodily movements.

Tendons are like rubber bands stretched over joints that keep
muscles attached to bones.

Ligaments are the soft tissues that attach bones to bones.

Ligaments are very similar to tendons. The difference is that tendons
attach muscles to bones. Both of these structures are made up of small fibers
of a material called collagen. The collagen fibers are bundled together to
form a rope-like structure. Ligaments and tendons come in many different
sizes, and like rope, are made up of many smaller fibers. The thicker the
ligament (or tendon) the stonger it is, for example the large Achilles tendon
is the most important tendon for walking, running, and jumping. Sometimes,
tendons and ligaments slide out of their spot at the joint and then quickly
snap back into place.

Topical Ibuuprofen

Q. What is ibuprofen?

A. Ibuprofen is medication called a Non-Steroidal Anti-Inflammatory
Drug, NSAID. Ibuprofen works by blocking the action of a substance in the body
called cyclo-oxygenase (COX). Cyclo-oxygenase is involved in the production of
various chemicals in the body, some of which are known as prostaglandins.
Prostagladins are produced in response to injury, certain diseases and various
conditions, which cause pain, swelling and inflammation. Ibuprofen blocks the
production of these prostaglandins and is therefore effective at reducing
inflammation and pain.

Q. What is topical ibuprofen?

A. Topical ibuprofen is used for 2 purposes; to help reduce
inflammation below the skin surface and alleviate nerve pain such as muscular
and joint pain, spasms, neck and low back pain, and pain associated with
strain or injury.

When ibuprofen is applied to the skin (topical application) it is
absorbed through the skin into the underlying tissues, where it reduces pain
and inflammation in the local area. NSAID's (non-steroid anti-inflammatory
drugs, such as ibuprofen) administered as cream, quickly penetrate through the
outer layer (of the skin) at the application site and reach highly effective
concentrations deep in the tissue such as tendons, ligaments, and muscles. It
is estimated that as much as 95% reach the target area. Blood levels of
topical NSAIDs are extremely low with no systemic side effects. By contrast,
oral NSAIDs lead to high blood levels but a lower concentration at the
targeted site of pain and are estiamted to be less than 5% in the soft tissue.

Q. Is it new?

A. Topical anti-inflammatory creams have been available in Europe
for 15 years and are extremely popular. There is four decades of research
studies done on topical ibuprofen.

Q. What is the advantage of using ibuprofen?

A. Topically, ibuprofen is very advantageous for several reasons.
The stomach and digestive tract are not exposed to the normal side effects of
oral pain relievers, such as stomach pain or increased risk of ulcers. The
risk of kidney and liver damage as well as cardiovascular problems, such as
heart attack and stroke, should be reduced because the active ingredients
remain in the skin and do not enter the blood to any real extent. The rest of
the body does not have to be exposed to unwanted medication--only the site of
pain.

Studies have shown that levels of topical ibuprofen can be 4 to 7 times
higher in the cartilage than oral ibuprofen. Results from oral preparations
delivered to a targeted site of pain are less than 5%. Onset of symptom relief
in some cases may be faster that oral preparations and relief may last longer.

Q. What is it used for?

A. Topical ibuprofen is used for pain and inflammation such as
muscle pain, rheumatic pain, sprains, strains, sports injuries, and pain from
non-serious arthritic conditions.

Q. Why combine glucosamine with ibuprofen?

A. The November 2003 issue of Journal of Pharmacology and
Experimental Therapeutics
reported the findings of Temple University
researchers that popular nutritional supplement glucosamine, administered with
ibuprofen, synergistically boosts the ability of the drug to relieve pain.

When compared on osteoarthritis ibuprofen works faster, within 2 weeks.
However, at eight weeks glucosamine is slightly more effective at reducing
pain.

Q.Are there any cautions is using topical ibuprofen?

A. Topical ibuprofen is for external use only. Do not apply to
broken skin. Avoid contact with the eyes and the moist membranes lining the
inside of certain parts of the body, such as the mouth and nasal passages
(mucous membranes). Rinse with cold water if accidental contact occurs. You
should not cover the area being treated with airtight dressings such as
bandages or other dressings. Wash your hands thoroughly after applying this
medication, unless the hands are the area being treated. Seek medical advice
from your doctor or pharmacist if your symptoms persist or worsen despite
treatment. If you experience any side effects from this medicine, in
particular a rash, stop using it and seek medical advice. Do not use if you
are allergic to ibuprofen. Ibuprofen cream is not recommended for children
under 12 years of age unless instructed by a doctor. Not indicated during
pregnany and breastfeeding unless approved by a doctor.

Q. Is topical ibuprofen more costly than oral ibuprofen?

A. Two studies have compared the cost of a topical NSAID with an
oral NSAID (generic ibuprofen), and examined costs over one month and three
months. Both studies concluded that total costs of topical NSAIDs were lower
than those of oral NSAIDs, and for the same reason--because of lower adverse
event rates. Higher acquisition costs for topical NSAIDs were offset by lower
adverse event costs which results in savings for the whole health economy.
Oral NSAIDs are associated with significant gastrointestinal adverse events.
Topical NSAIDs have much lower plasma concentrations, and are not associated
with higher rates of adverse events, or at any rate of gastrointestional
adverse events.

Topical
Versus Oral Ibuprofen

Topical
Administration---------------------------------Oral Administration

Low Blood Levels --------------------High Blood Levels

After a single application=500ng/ml -----After a single dose
(400mg)=20,000ng/ml

Levels in cartilage 4-7 x higher---------Levels in cartilage 4 x 7 lower
(proving direct absorption into joints does occur)

Levels in tendons several hundred x higher---Low levels in tendons

Low levels of Gastrointestional events-------High levels of
Gastrointestional adverse events

Q. What are the prescrtiption drugs for
arthritis?

A. Cox-2 Inhibitors, such as Celebrex and other Non-Steriod
Anti-Inflammatory Drugs, NSAIDs, such as ibuprofen (Motrin, Advil, Rufen,
Nuprin), naproxen (Naprosyn, Naprelan, Anaprox, Aleve), nabumetone (Relafen),
ketorolac, sulindac, and diclofenac (Cataflam, Voltaren). The class of drugs
known as Cyclo-oxygenase-2 inhibitors that emerged in the late 1990s for
dealing with arthritis pain, such as the brand names Celebrex and Vioxx, are
also considered part of the group of NSIADs.

Due to increased risk of heart attacks and strokes Vioxx was
voluntairly pulled off the market by its manufacturer.

Q. What are side effects of NSAIDs?

A. The major side effects of NSAIDs are related to their effects on
stomach and bowels (gastrointestional system). Some 10% to 50% of patients are
unable to tolerate NSAID treatment because of side effects, including
abdominal pain, diarrhea, bloating, heartburn, and upset stomach.
Approximately 15% of patients on long term NSAID treatment develope ulceration
of the stomach and duodenum. Even though many of these patients with ulcers do
not have symptoms and are unaware of their ulcers, they are at risk of
developing serious ulcer complications such as bleeding or perforation of the
stomach.

Q. How do NSAIDs work and how do they cause stomach problems?

A. Prostaglandins are natural chemicals which are involved in body
inflammation. By inhibiting the body's production of certain chemical
messengers (prostaglandins), NSAIDs decrease inflammation. However, certain
prostaglandins are also important in protecting the stomach lining from the
corrosive effects of stomach acid as well as playing a role in maintaining the
natural healthy condition of the stomach lining. These prostaglandins are
produced by an enzyme called Cox-1. By blocking the Cox-1 enzyme and
disrupting the production of prostaglandins in the stomach, NSAIDs can cause
ulcers and bleeding. Some NSAIDs have less effect on the stomach
prostaglandins than others, and, therefore a lower risk of ulcer formation.

Q. Are Cox-2 inhibitors safer?

A. Cox-2 inhibitor drugs are generally considered a safer
alternative to non-steroidal anti-inflammatory drugs (NSAIDs), but Cox
inhibitors are not without gastric side effects. In fact, the Cox-2 inhibitors
have been associated with gastrointestional side effects, particularly in
people with a history of gastrointestional disorders. In those who have
inflammatory bowel disease (Chron's disease or ulceratative colitis), Cox-2
inhibitors have been found to cause gastrointestional side effects, including
relapse of symptoms, requiring cessation of treatment in 25% of patients.

A new study published in the Journal of Immunology identifies a
potential long-term problem that could lead to cartilage and other tissue
degeneration if these drugs are taken over an extended time period. The
authors of this study found that Cox-2 inhibitors cause metabolic imbalances
that have been shown to play a role in the cartilage destruction and the
inflammation process.

Another problem with inhibiting the Cox-2 enzyme is that metabolic
imbalances occur, resulting in an overdose of byproducts that damage the
arterial wall and induce arterial blood clotting.

Q. What are the side effects of oral NSAIDs?

A. Prehaps the most notable side effect for people suffering with
chronic joint pain is that NSAIDs have a propensity to make cartilage
deteriorate, according to an article in the American Journal of Medicine
as early as 1987.

(Brandt KD. Effects of nonsteridol anti-inflammatory
drugs on chondrocyte metabolism in vitro and in vivo. Am J Med. 1987 Nov
20;83(5A):29-34.)

There are also very considerable evidence that oral NSAIDs
produce significant upper gastrointestional adverse events because of
gastroduodenal ulceration, and, in some cases, bleeding. These require
hospital treatment or prophylaxis with proton pump inhibitors to prevent these
adverse events. Gastrointestional adverse events are known NOT to be
associated with topical NSAID use.

General risks: gastrointestional side effects, renal insufficiency,
hepatic toxicity, exacerbation of asthma, sodium retention, raised blood
pressure and resistance to anti-hypertensive drugs, and increased risk of iron
deficency or iron deficiency anemia.

Around 40% of hospital admissions with upper gastrointestional bleeding,
and 40% of associated deaths in older people are related to NSAID use.

Recent research also has found that the use of NSAIDs increases the risk
of erectile dysfunction in middle-age and elderly men.

Q. What is the pain patch?

A. The FDA has issued a health advisory regarding the safe use of
fentanyl skin patches (brand name Duragesic) in response to reports of deaths
in patients using this potent narcotic medication for pain management.

The FDA is conducting an investigation into the deaths associated with
these pratches. It's unclear if the deaths are due to inappropiate use of the
patch or factors related to the quality of the product, according to the
advisory.

Deaths and overdoses have occured in patients using both the brand name
product Duragesic and the generic product Fentanyl. The directions for using
the Fentanyl skin patch must be followed exactly to prevent death or other
serious side effects from overdosing with Fentanyl, according to the FDA.

Research Highlights on Topiocal Ibuprofen


Osteoarthritis:

* BMC Family Practice, 2004.

Results of twenty-six trials on 2,853 patients for evaluation of
efficacy of topical NSAIDs. A 10 cm strip of 5% Ibuprofen cream for 7 days on
Osteoarthritic knees, reduced pain in motion, pain at rest, and overall pain
without adverse events.

* BMJ 2004.

Topical NSAIDs relieve osteoarthritis pain for only two weeks but
there is no evidence that topical NSAIDs cure arthritis pain long term.

Acute
Conditions:

* BMJ, January 1998.

Reported that topical NSAIDs were effective in relieving pain in
acute conditions like sprains ans strains. Authors Conclusions: Topical
NSAIDs were effective and safe in treating acute painful conditions for one
week.

*J Accid Energ Med, Sept 1994.

Evaluation of topical cream in the treatment of acute sprains. One
hundred patients who presented to the accident and emergency (A&E) department
with an acute ankle sprain. Patients using the topical ibuprofen cream had
significant reduction in pain scores over the first 48 hours of treatment.

*Journal of Clinical Pharmacy & Therapeutics. (December 2002)

Comparative efficancy of a proprietary topical ibuprofen gel and oral
ibuprofen in acute soft tissue injuries. Summary: The efficacy of a
novel, proprietary topical formation of ibuprofen 5% gel and ibuprofen 400 mg
tablets (1200 mg daily) acute soft tissue injuries. The two treatments showed
similar efficancy. In summary: Ibuprofen gel shows similar efficancy to
oral ibuprofen 400 mg and may offer improved tolerability.


Rheumatology

* Health Technol Asses, 1997

Topical NSAIDs are effective in rheumatological conditions with few
adverse events.

Absorption

* German journal, 1999

Essentially the entire oral dose is excreted in urine during 24
hours but only .55% of the topical dose is excreted during 24 hours,
suggesting that if target tissue concentrations correlate directly with the
degree of pain relief, patients with pain caused by dermal or subcutaneous
tissue damage will have greater pain relief after topical administration of
ibuprofen with less systemic side effects

Additionally, some patients with muscle pain may also experience pain
relief from topical ibuprofen.


Glucosamine

Q. What is Glucosamine?

A. Glucosamine is a natural remedy that has been found to be useful
in promoting healthy joints. In Europe glucosamine is approved as a drug for
osteoarthritis. It is a natural substance made by the body that provides the
raw material needed to repair the connective tissue found in skin, tendons,
ligaments, and joints. Animal studies show that when an injury occures levels
of glucosamine in the body increases.

Q. Are there studies proving Glucosamine is effective?

A. Supplemental glucosamine appears to provide the material
necessary for joint repair. Research has also demonstrated that glucosamine
also has the ability to delay the progression of the disease. It does this by
inhibiting certain enzymes, which destroy the cartilage. Furthermore, it has
been shown to relieve symptoms even for weeks after termination of the
treatment.

Many studies confirm the efficacy of glucosamine. Recently all of the
published studies done on glucosamine were reviewed. In all, there were 13 of
these studies (six involving glucosamine and seven involving chondroitin
sulfate). All 13 studies found positive results in hip and knee osteoarthritis.

Even the prestigious, Journal of the American Medical Association
(JAMA)
in the March 15, 2000 issue, reviewed all known studies on
glucosamine and chondroitin in the treatment of arthritis. The conclusion
of the authors was: "Trials of glucosamine and chondroitin preparations for
osteoarthritis symptoms demonstrate moderate to large effects..."

Glucosamine alone or in conjunction with chondroitin sulfate may have
the ability to repair and improve joint function in addition to providing pain
relief.

Specific Citations are:

* Glucosamine provides the raw material needed to
repair the connective tissue found in skin, tendons, ligaments, and joints
(McCarty MF 1996; Zupanets IA 2002)
.

* Animal studies show that levels of glucosamine increase in injured
tissue during healing (Lehto M 1985).

*Glucosamine also inhibits certain enzymes, which destroy the
cartilage, e.g. collagenase and phospholipase. Glucosamine delays the
progession of the disease and relieves symptoms even for weeks after
termination of the treatment. (Qiu GX, et al.)

*Efficancy and safety of glucosamine sulfate versus ibuprofen in
patients with knee osteoarthritis.( Arzneimittelforschung
1998 May;48(5):469-74.)

*Long term treatment with glucosamine sulfate retarded the
progression of knee osteoarthritis, possibly determining disease modification
and was safe. Glucosamine sulfate use and progression of knee osteoarthritis:
a 3-year, randomized, placebo-controlled, double-blind study.
(Pavelka K, Gatterova J, Olejarova M, et al. Arch Interm Med. 2002 Oct
14;
162(18):2113-23.

Q.How do we know that glucosamine and chondroitin are
effective used topically?

A. Published studies on topical glucosamine have demonstrated
outcomes of reduced joint pain, less stiffness and increased function of the
affected joints.

J Rheumatol. 2003 Nov;30(11)2512. A radonmized,
double blind, placebo controlled trial of a topical cream containing
glucosamine sulfate, chondroitin sulfate, and camphor for ostearthritis of the
knee. CONCLUSION: Topical applicatiion of glucosamine and chondroitin
sulfate is effective in relieving the pain from OA of the knee and improvement
within 4 weeks.

Q. Where does it come from?

A. The glucosamine used in supplements is typically derived from the
shells of crabs, although a corn source is also available.

Q. Why should glucosamine be used in conjunction with MSM?

A. In a new study, the combination of glucosamine with MSM was found
to be more effective in improving the signs and symptoms of osteoarthritis
than the use of either agent alone. The study authors concluded that the
combination of glucosamine with methylsulfonylmethane (MSM) provides better
and more rapid improvement in patients with osteoarthritis than either agent
alone.

Usha PR, Naidu MU. Randomized, double-blind, parallel,
placebo-controlled study of oral glucosamine, methylsulfonylmethane and their
combination in osteoartritis. Clin Drug Invest. 2004 Jun;24(6):353-63.

Q. How long does it take to work?

A. As with most natural remedies the therapeutic effect of
glucosamine usually takes some weeks to appear (1-8 weeks). Once achieved, it
tends to persist for a notable time even after discontinuation of the
treatment.

Q. Why combine Glucosamine with Ibuprofen?

A. The November 2003 issue Journal of Pharmacololgy and
Experimental Therapeutics
reported that the findings of Temple University
researchers that the popular nutritional supplement glucosamine, administered
with ibuprofen, synergistically boosts the ability of the drug to relieve pain.

When compared on osteoarthritis ibuprofen works faster, within 2 weeks.
However, at eight weeks glucosamine is slightly more effective at reducing
pain.

Q. What about the safety of Glucosamine?

A. Glucosamine is generally expected to be safe since it is a
substance normally used by the body.

Q. How does taking Glucosamine compare to taking NSAIDs for arthritic
pain?

A. Clinical evidence suggests that glucosamine helps maintain the
joint space and may help rebuild damaged cartilige. By contrast, oral
NSAIDs have a propensity to make cartilage deteriorate. Glucosamine also
inhibits certain enzymes that destroy cartliage. By blocking pathogenic
mechanisms that lead to joint degeneration, glucosamine delays the progression
of osteoarthritis and relieves symptoms even for weeks after termination of
the treatment.

Qiu GX, Gao SN, Giacovelli G., Rovati L, Setnikar I.
Efficacy and safety of glucosamine sulfate versus ibuprofen in patients with
knee osteoartisis. Arzneimit-telforschung. 1998 May;48(5):469-74

.

Q. Are there contraindications to glucosamine?

A. There are no known contraindications to glucosamaine
supplementaion. Glucosamine appears safe and has few short-term side effects.
Pregnant women, children, and very elderly people should avoid glucosamine
since no studies among these specific populations exists. Patients taking
blood-thinners should be extremely careful if they take glucosamine combined
with chondroitin.

Q. Are there side effects to Glucosamine?

A. Side effects that have been reported are on oral glucsoamine and
are mainly mild gastrointestional complaints such as heartburn, epigastric
distress and diarrhea. No allergic reactions have been reported including
sulfa-allergic reactions to glucosamine sulfate. These have not been measured
or demonstrated topically.


Chondroitin

Q. What is Chondroitin sulfate?

A. Chondroitin sulfate is a major component of cartilage. As in the
case of glucosamine, chondroitin sulfate also works by attracting water into
the cartilage matrix and stimulating the production of cartilage. This is
essential in order for healthy cartilage to recieve nutrients and to protect
the cartilage from wear and tear.

Another similarity is that chondroitin sulfate is also believed to
prevent enzymes from dissolving cartilage, slowing progress of joint
degradation. Recent studies have shown very good results from long-term
treatment with chondroitin sulfate, reducing pain and increasing range of
motion.

Q. Are there side effects asssociated with taking chondroitin
sulfate?

Side effects that have been reported are mainly mild
gastrointestional complaints such as heartburn, epigastric distress and
diarrhea. No allergic reactions have been reported including sulfa-allergic
reactions to glucosamine sulfate.

Q. Where does chondroitin sulfate come from?

A. Chondroitin sulfate is generally derived from cow cartilage, but
porcine (pig) and even chicken cartilage has been used and algae are another
potential source.

Q. Are there contraindications or interactions to chondroitin
sulfate?

A. There are no known contraindications. There are no known drug,
nutrient, food or herb interactions. Chitosan (see Chitosan) may form
complexes with chondroitin sulfate decreasing its absorption. Therefore,
chondroitin sulfate should not be used concomitantly with chitosan.

Q. Are there any side effects to chondroitine sulfate?

A. Because of insufficient safety data, children, pregnant women and
nursing mothers should avoid using chondroitin sulfate. Because of the
theoretical possibility that chondroitin sulfate may have anti-thrombotic
activity, those taking warfarin and those with hemophilia should exercise
caution in its use. Those who need to restrict their salt intake should, if
they use chondritin sulfate, use salt-free preparations.

Side effects from oral usage that have been reported are mostely of the
mild gastrointestinal variety, such as epigastric distress, nausea and
diarrhea. No sulfa-allergic reactions or other allergic reactions have been
reported. These have not been measured topically.

MSM

Q. What is MSM?

A. Methylsulfonymethane, abbreviated MSM, is an organic
sulfer-contining compound. MSM occurs naturally in a variety of fruits,
vegetables, grains and in animals, including humans in at least trace amounts.
MSM has also been found in such plants as Equisetem arvense, also known
as horsetail. MSM is produced by the body as a result of the foods we eat.

MSM finds its way into the collagen of skin, joints, and blood vessels.
It is also incorporated in the keratin of hair and nails. The body's
concentration of MSM tends to decrease with age. Some research suggests a
minimum concentration of MSM must be maintained in the body to preserve normal
function and structure.

Q. What does MSM do?

A. MSM is a natural remedy that may benefit individuals with
arthritis, act as a natural analgesic and anti-inflammatory substance. MSM is
a small but highly effective molecule that may inhibit pain impulses along
nerve fibers, quell inflammation, increase blood supply, reduce muscle spasms,
and soften scar tissue. MSM is thought to relieve pain and inflammation in
osteoarthritis, rheumatoid arthritis, lupus, scleroderma, and fibromyalgia. It
has also been reported to be helpful in allergies, back pain, headaches,
temporomandibular joint dysfunction (TMG), Tendonitis, and more.

Q. What so studies on MSM show?

A. Animal studies have shown that joints affected by osteoarthritis
have lower sulfer content, and that arthritic mice given MSM experience less
joint degeneration. In a human trial in people with osteoarthritis, subjects
who recieved MSM experienced significant pain relief.

* Murav'er I, Venikova MS, Plenskovskaia GN, Riazantseva
TA, Sigidin I. Effect of dimethyl sulfoxide and dimenthyl sulfone on a
destructive process in the joints of mice with spontaneous arthritis. Patol
Fiziol Eksp Ter.
1991 Mar-Apr;(2):37-9.

* Lawrence RM. Methysulfonylmethane (MSM): a
double-blind study of its use in degenerative arthritis. Int J Anti-Aging
Med.
1998;1:50.

* Jacob SW, Lawrence RM, Zuker M. The Mircle of
MSM. New York: Berkley Books, 1999.

* Richmand VL. Incorporation of
methylsulfonymethane sulfur into guinea pig surem proteins. Life Sci.
1986; 39:263-268.

Q. Are there any safety concerns or contraindications for MSM?

A. MSM is thought to be safe and nontoxic. There are no known
contrindications. MSM should be avoided by pregnant women and nursing mothers
due to lack of studies. It is generally believed that people who are allergic
to sulfa drugs or do not tolerate sulfite preservatives in foods need not be
concerned about the use of MSM and glucosamine sulfate--that these do not give
rise to allergic reactions. However, there are reports of individulas who are
reactive, so caution is advised.


Bromelain

Q. What is Bromelain?

A. Bromelain is an enzyme derived from pineapple stems. It is
believed to inhibit the root cause of inflammation within the body by
adjusting the hormones that trigger inflammation. Bromelain's
anti-inflammatory enzyme is thought to possess the ability to break down or
dissolve proteins which help to reduce muscle and tissue swelling, especially
following injuries or surgery, and as indicated by research dental surgery and
musculoskeltal trauma.

Q. Is there scientific research on Bromelain?

A. Yes as cited below:

* (MacKay D. et al 2003) Use of oral bromelain over the
postoperative period results in faster resolution of swelling and decreased
dependence of analgesics in fracture patients (Kamenicek V et al 2001).

* Similar resutls have been recorded after dental
surgery (Tassman G et al 1964) and musculoskeletal trauma (Masson M 1995).

* Masson M. (Bromelain in blunt injuries of the
locomotor system. A study of observed applications in general practice.)
Fortschr Med.
1995 July 10;113(19):303-6.