COX-2 inhibitors

Related Terms

Analgesic, anti-inflammatory, arthritis, biological mediators, cardiovascular events, Celebrex?, COX, COX 1, COX 2, COX enzymes, cyclooxygenase, edema, eicosanoid-depressing inflammation, fluid retention, heart attack, inflammation, liver damage, nonsteroidal anti-inflammatory drugs, NSAIDS, osteoarthritis, pain relief, pain relievers, prostaglandins, rheumatoid arthritis, stomach ulcers, stroke, swelling, ulcers.

Background

Selective COX-2 inhibitors are a type of nonsteroidal anti-inflammatory drug (NSAID) that are used to reduce inflammation (swelling) and pain (analgesic). The term "nonsteroidal" is used to distinguish the drugs from steroids, which have similar eicosanoid-depressing and anti-inflammatory properties. NSAIDs are non-narcotic and are therefore non-addictive.
There are two types of NSAIDS: traditional (non-selective) NSAIDs and selective COX-2 inhibitors. Traditional NSAIDs, such as ibuprofen (Motrin? or Advil?), block the actions of both cyclooxygenase-1 (COX-1) and cyclooxygenase-2 (COX-2) enzymes, the key enzymes that stimulate inflammation. COX-1 protects the stomach lining from harsh acids and digestive chemicals and helps maintain kidney function. The body produces COX-2 when the joints are injured or inflamed.
Selective COX-2 inhibitors are prescription drugs that only target the COX-2 enzyme. They are commonly used to treat pain and inflammation associated with arthritis.
Celecoxib (Celebrex?) is currently the only U.S. Food and Drug Administration (FDA) approved COX-2 inhibitor. Two other selective COX-2 inhibitors, rofecoxib (Vioxx?) and valdecoxib (Bextra?), were removed from the market after reports of serious side effects such as heart attack and stroke.
Celebrex? has also been linked to an increased risk of serious heart-related problems, including heart attack and stroke. It is also well documented that COX-2 inhibitors increase the risk of stomach bleeding, which can be life threatening. It appears that these risks also apply to traditional NSAIDs as well. Therefore, the FDA requires that all NSAIDs, including COX-2 inhibitors, print serious warning labels that highlight the risk of potential heart-related side effects and stomach bleeding. The labels must also state that patients who have recently had heart surgery should not take NSAIDs.

Author information

This information has been edited and peer-reviewed by contributors to the Natural Standard Research Collaboration (www.naturalstandard.com).

Bibliography

American Academy of Orthopedic Surgeons. .
Medinfo. .
National Institute for Arthritis and Musculoskeletal and Skin Diseases. .
Natural Standard: The Authority on Integrative Medicine. .
U.S. Food and Drug Administration. .

Integrative therapies

Good scientific evidence:
Bromelain: Several preliminary studies suggest that when taken by mouth, bromelain can reduce inflammation or pain caused by inflammation. Better quality studies are needed to confirm these results.
Avoid if allergic to bromelain, pineapple, honeybee, venom, latex, birch pollen, carrots, celery, fennel, cypress pollen, grass pollen, papain, rye flour, wheat flour, or other members of the Bromeliaceaefamily. Use cautiously with history of bleeding disorder, stomach ulcers, heart disease, liver disease or kidney disease. Use cautiously before dental or surgical procedures or while driving or operating machinery. Avoid if pregnant or breastfeeding due to insufficient scientific evidence of safety. Bromelain may cause abnormal uterine bleeding.
Comfrey: In vitro studies have found that comfrey may have anti-inflammatory effects. Clinical trials investigating topical application of comfrey-containing creams have found significant reductions in inflammation and pain associated with sprains and muscle injuries. Overall, these studies have been well designed, although some improvements in reporting are needed.
Avoid if allergic/hypersensitive to comfrey, its constituents, or members of the Boraginaceae family. Avoid oral comfrey due to hepatotoxic and carcinogenic (cancer-causing) pyrrolizidine alkaloids; oral use has caused death. Avoid topical comfrey on broken skin due to hepatotoxic and carcinogenic pyrrolizidine alkaloids. Avoid topical comfrey in individuals with or at risk for liver disorders, cancer, or immune disorders. Use topical creams containing comfrey cautiously if taking anti-inflammatories or cytochrome P450 3A4-inducing agents. Use extreme caution when using topical creams containing comfrey for extended periods. Avoid topical comfrey in pregnant or breastfeeding due to potential for absorption of toxic compounds.
Hypnotherapy: Hypnotherapy has been studied in the management of pain, including low back pain, surgery-related pain, cancer-related pain, dental procedure-related pain, burn pain, repetitive strain injury, disorders of the jaw joint, sickle cell disease-related pain, irritable bowel syndrome, oral mucositis (inflammation of the mouth and gastrointestinal tract), tension headache, and chronic pain from various causes. Various hypnotherapy approaches have been used, and it is not clear which technique or length of treatment is optimal. Therefore, although the existing research is promising, better-designed trials are necessary before a strong recommendation can be made.
Use cautiously with mental illnesses like psychosis/schizophrenia, manic depression, multiple personality disorder or dissociative disorders. Use cautiously with seizure disorders.
Music therapy: Music therapy helps in a wide range of pain conditions, primarily by its ability to improve mood, encourage relaxation, and elevate pain threshold. There is evidence of benefit for pain in cancer, neonates in intensive care, burn care, general post-surgery, hospice patients, osteoarthritis, post-anesthesia care, open-heart surgery recovery, and coronary artery bypass graft (CABG) surgery. However, results are not universal. Studies have found no or unclear benefits in stroke patients during upper extremity joint exercises, tissue biopsy or port placement or removal in cancer, musculoskeletal trauma, inquinal hernia (small part of the intestine, bladder or abdominal tissue that pushes into the groin muscles) surgery, and abdominal hysterectomy. Thus, music therapy may be less helpful with more severe pain.
Physical therapy: Physical therapy has been used to treat a wide variety of pain syndromes, including patellofemoral pain syndrome (chronic knee pain), wrist pain, post-operative pain, and chronic pain. Despite some mixed evidence, there are several trials that compare physical therapy techniques to placebo controls for the treatment of patellofemoral pain syndrome that have found beneficial effects. Also, continuous low-level heat wrap therapy may be helpful in common conditions causing wrist pain and impairment. Long-term studies with more standardized outcome measures would help make a stronger recommendation.
Not all physical therapy programs are suited for everyone, and patients should discuss their medical histories with qualified healthcare professionals before beginning any treatments. Based on the available literature, physical therapy appears generally safe when practiced by a qualified physical therapist. However, complications are possible. Treatment options should be considered carefully. Physical therapy may aggravate pre-existing conditions. Persistent pain and fractures of unknown origin have been reported. Physical therapy may increase the duration of pain or cause limitation of motion. Pain and anxiety may occur during the rehabilitation of patients with burns. Both morning stiffness and bone erosion have been reported in the physical therapy literature although causality is unclear. Erectile dysfunction has also been reported. Physical therapy has been used in pregnancy, specifically to treat women with pelvic girdle pain during pregnancy and at three, six, and 12 months postpartum. Reports of major adverse effects are lacking the available literature, but caution is advised nonetheless. All therapies during pregnancy and breastfeeding should be discussed with a licensed obstetrician/gynecologist before initiation.
Therapeutic touch: Therapeutic touch may reduce pain and improve joint mobility in people with osteoarthritis (hollow, brittle bones), decrease pain and anxiety caused by burns, and improve chronic muscle and joint pain in elderly patients. Preliminary research reports that patients treated with therapeutic touch may need less pain medication after surgery. However, most studies of therapeutic touch have not been well designed, and therapeutic touch has not been clearly compared to common pain treatments such as pain relieving drugs. Further research is needed before a firm conclusion can be drawn.
Therapeutic touch is believed to be safe for most people. Therapeutic touch should not be used for potentially serious conditions in place of more proven therapies. Avoid with fever or inflammation, and on body areas with cancer.
Unclear or conflicting scientific evidence:
Aconite: There is limited data on the use of aconite or any of its derivatives in treating pain. Homeopathic aconite significantly relieved pain and discomfort after surgery in a randomized, double-blind, placebo-controlled study. Further information is needed to confirm these results.
Aconite is highly toxic and is not safe for human consumption. Avoid with heart disease, heart dysfunction, irregular heartbeat, hemodynamic instability (abnormal blood flow), gastrointestinal disorders, ulcers, reflux esophagitis, ulcerative colitis, spastic colitis, and diverticulosis (intestinal disorder). Use cautiously with diabetes and suicidal tendencies. Avoid if younger than 18 years old. Avoid if pregnant or breastfeeding.
Acupressure: Acupressure with aromatic essential oils (lavender) may reduce pain intensity, stiffness and stress in patients with neck pain for up to one month. Studies also report that acupressure provides pain relief to patients after surgeries. This research suggests that acupressure may be as effective as intravenous pain medications. However, further evidence is needed from well-designed trials before firm conclusions can be drawn.
With proper training, acupressure appears to be safe if self-administered or administered by an experienced therapist. No serious long-term complications have been reported, according to scientific data. Hand nerve injury and herpes zoster ("shingles") cases have been reported after shiatsu massage. Forceful acupressure may cause bruising.
Acupuncture: There is insufficient evidence for or against use of acupuncture in pain associated with burns.
There has been limited research on acupuncture for cancer pain, and the research that was done was shown to have mixed results. More studies are needed to determine potential benefits. Higher-quality studies suggest potential benefit for musculoskeletal pain, but overall, studies have been poorly designed. There is insufficient evidence available for or against acupuncture in craniofacial pain. Results have been mixed for the effects of both acupuncture and electroacupuncture on pain following surgery (knee arthroscopy, back, abdominal, gastroscopy, breast, pulmonary). There is insufficient available evidence for or against acupuncture for post-surgical pain.
Needles must be sterile in order to avoid disease transmission. Avoid with valvular heart disease, infections, bleeding disorders, or with drugs that increase the risk of bleeding (anticoagulants), medical conditions of unknown origin, and neurological disorders. Avoid on areas of the body that have received radiation therapy. Use cautiously with pulmonary disease (like asthma or emphysema). Use cautiously in elderly or medically compromised patients, diabetics, or with history of seizures. Avoid electroacupuncture with arrhythmia (irregular heartbeat) or in patients with pacemakers. Avoid if pregnant.
Acustimulation: A study of patients recovering from abdominal surgery found that both high- and low-intensity levels of acustimulation reduced their need for pain medication. However, the higher intensity stimulation was more effective. More studies are needed to confirm these results.
The only known side effect of acustimulation devices is slight skin irritation under the electrodes when the wristband is used. Switch wrists to avoid this reaction. Acustimulation devices should only be used on the designated area. Use cautiously with pacemakers. Avoid if the cause of medical symptoms is unknown. Keep acustimulation devices out of the reach of children.
L-Arginine: Preliminary research suggests that ibuprofen-arginate may be a beneficial treatment for pain. Further research is needed to confirm these results.
Avoid if allergic to arginine. Avoid with history of stroke or liver or kidney disease. Use cautiously if taking blood-thinning drugs (Coumadin?), blood pressure drugs, or herbs or supplements with similar effects. Check blood potassium levels. Avoid if pregnant or breastfeeding.
Black cohosh: There is not enough human research about the use of black cohosh for painful joints in rheumatoid arthritis or osteoarthritis.
Use cautiously if allergic to members of the Ranunculaceaefamily including buttercups or crowfoot. Avoid with hormone conditions (breast cancer, ovarian cancer, uterine cancer, and endometriosis). Avoid if allergic to aspirin products, nonsteroidal anti-inflammatory drugs (NSAIDs), blood-thinners (warfarin), or with history of blood clots, stroke, seizures, or liver disease. Stop use before surgery/dental/diagnostic procedures with bleeding risk and avoid immediately after these procedures. Avoid if pregnant or breastfeeding.
Cat's claw: Several laboratory and animal studies suggest that cat's claw may reduce inflammation, and this has led to research of cat's claw for conditions such as rheumatoid arthritis. Large, high-quality human studies are needed comparing effects of cat's claw alone versus placebo, before a conclusion can be drawn.
Avoid if allergic to Cat's claw or Uncaria plants or plants in the Rubiaceae family, such as gardenia, coffee, or quinine. Avoid if history of conditions affecting the immune system (such as AIDS, HIV, some types of cancer, multiple sclerosis, tuberculosis, rheumatoid arthritis, lupus). Use cautiously with bleeding disorders, history of stroke, or with drugs that may increase the risk of bleeding. Stop use two weeks before surgery/dental/diagnostic procedures with bleeding risk, and do not use immediately after these procedures. Avoid if pregnant or breastfeeding. Cat's claw may be contaminated with other Uncaria species. Reports exist of the potentially toxic Texan grown plant Acacia gregii being substituted for cat's claw.
Chiropractic: There are more than 150 published human trials and case reports that detail the use of chiropractic manipulation in patients with low back pain. Results are variable, with some studies reporting benefits, and others suggesting no significant effects. Most trials are not well-designed or reported, with inconsistent use of definitions of disease, techniques, and measured outcomes. There is also insufficient evidence on the efficacy of chiropractic manipulation for chronic pelvic pain (CPP), shoulder pain, frozen shoulder, or rotator cuff injuries. Better research is necessary before definitive conclusions can be reached.
Use extra caution during cervical adjustments. Use cautiously with acute arthritis, conditions that cause decreased bone mineralization, brittle bone disease, bone softening conditions, bleeding disorders or migraines. Use cautiously with the risk of tumors or cancers. Avoid with symptoms of vertebrobasilar vascular insufficiency, aneurysms, unstable spondylolisthesis or arthritis. Avoid with agents that increase the risk of bleeding. Avoid in areas of para-spinal tissue after surgery. Avoid if pregnant or breastfeeding due to a lack of scientific data.
Clove: Preliminary research reports oil of clove combined with zinc oxide paste to be effective for dry socket. The benefits of clove alone need to be studied before a firm conclusion can be made.
Avoid if allergic to Balsam of Peru, clove, eugenol, or some licorice products and tobacco (clove cigarette) products. Avoid with history of seizures, stroke, or with liver damage. Use cautiously with medications for diabetes, with bleeding problems, or male impotence. Stop use two weeks before surgery/dental/diagnostic procedures with bleeding risk and do not use immediately after these procedures. Use cautiously if driving or operating machinery. Avoid if pregnant or breastfeeding.
Coleus: There is a lack of sufficient data concerning the use of coleus for its anti-inflammatory effects in patients recovering after cardiopulmonary bypass (open-heart surgery). Randomized, clinical trials are warranted.
Avoid if allergic to coleus. Use cautiously with antidepressants (such as Prozac?), blood pressure drugs, blood-thinners, pain relievers, anticoagulants (such as warfarin), ibuprofen, blood sugar drugs, bronchodilators, heart drugs (such as anti-arrhythmics), drugs dependent on stomach pH (such as ketoconazole), thyroid drugs, bladderwrack, garlic, Ginkgo biloba, St. John's wort, and other herbs or supplements with similar effects.
Comfrey: One study has investigated the effects of topical application of a comfrey-containing cream on pain associated with myalgia. Improvements in pain at rest and in motion were noted. Further well- designed clinical trials in this field are required before a firm conclusion can be made.
Avoid if allergic or hypersensitive to comfrey, its constituents or members of the Boraginaceae family. Avoid oral comfrey due to hepatotoxic and carcinogenic (cancer-causing) pyrrolizidine alkaloids; oral use has caused death. Avoid topical comfrey on broken skin due to hepatotoxic and carcinogenic pyrrolizidine alkaloids. Avoid topical comfrey in individuals with or at risk for hepatic disorders, cancer or immune disorders. Use topical creams containing comfrey cautiously if taking anti-inflammatory medications or cytochrome P450 3A4-inducing agents. Use extreme caution when using topical creams containing comfrey for extended periods. Avoid if pregnant or breastfeeding.
Dandelion: Animal studies suggests that dandelion root may possess anti-inflammatory properties. However, there are no well-conducted human studies currently available in this area.
Avoid if allergic to chamomile, feverfew, dandelion, honey, yarrow, or any related plants, such as aster, daisies, sunflower, chrysanthemum, mugwort, ragweed, or ragwort. Avoid if taking aspirin or anti-inflammatories (NSAIDs like ibuprofen), blood thinners, diuretics (like hydrochlorothiazide), or lithium. Use cautiously with diabetes or bleeding disorders, gastroesophageal reflux disease (GERD), kidney or liver diseases, or with history of stroke or electrolyte disorders. Monitor potassium blood levels. Stop use two weeks before surgery/dental/diagnostic procedures with bleeding risk and do not use immediately after these procedures. Avoid if pregnant or breastfeeding.
Euphorbia: Euphorbia balsamifera has been studied in patients with acute dental pulpitis, and may be comparable to that of pulpal nerve caustics. Additional research is necessary before a firm conclusion can be made.
Avoid if allergic or hypersensitive to pollen from Euphorbia fulgens. Use cautiously with history of Epstein Barr virus infection or stomach conditions. Avoid if pregnant or breastfeeding.
Eyebright: Limited evidence from animal research suggests that several iridoid glycosides isolated from eyebright, particularly aucubin, possess anti-inflammatory properties comparable to those of indomethacin. The mechanism of action may be the inhibition of thromboxane-synthase. The clinical relevance in humans is unclear, and there are no known human clinical observations or controlled trials in this area. Therefore, there is currently insufficient evidence concerning the use of eyebright as an anti-inflammatory agent.
Avoid if allergic to eyebright, any of its constituents or members of the Scrophulariaceae family. Use cautiously as an eye treatment, particularly homemade preparations, due to the risk of infection if not sterile. Use cautiously with diabetes and drugs that are broken down by the liver. Avoid if pregnant or breastfeeding.
Focusing: Early evidence suggests focusing may improve medical symptoms and activity in individuals with chronic pain. More research is needed .
Side effects have rarely been reported, but patients should consult their qualified healthcare practitioners before making decisions about medical conditions and practices. Individuals with severe emotional difficulties should not abandon proven medical and psychological therapies, but rather choose focusing as a possible adjunct.
Healing touch: Preliminary data from two case series suggest that one session of healing touch (HT) leads to a reduction in pain and anxiety from immediately before to immediately after the session. Formal studies are needed to determine the role of HT in the treatment of chronic pain. Data from two small studies are inconclusive as to whether HT can benefit patients with pain after surgery. Studies of better design are needed before a definitive conclusion can be made.
HT should not be regarded as a substitute for established medical treatments. Use cautiously if pregnant or breastfeeding.
Lavender: Preliminary research suggests that the impression of pain intensity and unpleasantness may be reduced after treatment with lavender therapy. Other research has shown that lavender aromatherapy may be effective when used with acupressure for short-term relief of lower back pain. Further research is needed before firm conclusions can be drawn.
Avoid if allergic or hypersensitive to lavender. Avoid with history of seizures, bleeding disorders, eating disorders (anorexia, bulimia), or anemia (low levels of iron). Avoid if pregnant or breastfeeding.
Magnet therapy: Preliminary research reports reductions of pain in women with chronic refractory pelvic pain using magnet therapy. Well-designed studies are needed in this area before a conclusion can be drawn.
Initial studies report significant reductions in foot burning, numbness, tingling, and walking-induced foot pain with the use of static magnetic shoe insoles. Despite methodological weaknesses with the design and reporting of available studies, these findings are promising. Effects are reported to take three to four months. High-quality research is necessary in this area before a firm conclusion can be drawn.
Pulsed electromagnetic therapy and magnetic "necklaces" have been used and studied in people with chronic neck pain. Research is limited and not well designed. Better studies are necessary before a firm conclusion can be drawn.
Preliminary research reports improved muscle strength and pain in post-polio patients receiving therapy with static magnetic fields. Additional research is necessary before a firm conclusion can be drawn.
Initial evidence has failed to show improvements in knee pain with the use of magnet therapy. However, due to methodological weaknesses with this research, the conclusions cannot be considered definitive.
Avoid with implantable medical devices like heart pacemakers, defibrillators, insulin pumps, or hepatic artery infusion pumps. Avoid with myasthenia gravis or bleeding disorders. Avoid if pregnant or breastfeeding. Magnet therapy is not advised as the sole treatment for potentially serious medical conditions, and should not delay the time to diagnosis or treatment with more proven methods. Patients are advised to discuss magnet therapy with their qualified healthcare providers before starting treatment.
Massage: Several human trials report temporary improvements in low back pain with various massage methods. A recent study showed slightly more efficacy for traditional therapy. However, the additional benefits of massage may add to its value for holistic nursing practice. Preliminary evidence also suggests that massage alone, or in combination with mindful-based stress reduction, may be beneficial for patients with chronic pain. Additional research is necessary to confirm these results. Avoid with bleeding disorders, low platelet counts, or if on blood-thinning medications (such as heparin or warfarin/Coumadin?). Areas should not be massaged where there are fractures, weakened bones from osteoporosis or cancer, open/healing skin wounds, skin infections, recent surgery, or blood clots. Use cautiously if history of physical abuse or if pregnant or breastfeeding. Massage should not be used as a substitute for more proven therapies for medical conditions. Massage should not cause pain to the client.
Pet therapy: Based on preliminary study, canine visitation therapy (CVT) may be an effective adjunct to traditional pain management for children. More high-quality studies are needed to make a firm conclusion. .
Avoid if allergic to animal dander. Use only animals that have had veterinary screening, particularly in situations involving young children, frail elderly, or people immunocompromised or with medical conditions making them vulnerable to infection. Do not provide unsupervised use of animals with the severely mentally ill and very young children. Avoid with fear of animals or traumatic history with animals.
Physical therapy: Complex regional pain syndrome involves persistent pain, allodynia (light touch causing pain), and vasomotor signs. Early evidence suggests that physical therapy may have a better effect than occupational therapy or no treatment for the reduction of pain in some patients. Physical therapy, especially home-based programs, may also be more cost-effective. Additional research is needed.
Not all physical therapy programs are suited for everyone, and patients should discuss their medical histories with their qualified healthcare professionals before beginning any treatments. Based on the available literature, physical therapy appears generally safe when practiced by a qualified physical therapist. However, complications are possible. Treatment options should be considered carefully. Physical therapy may aggravate pre-existing conditions. Persistent pain and fractures of unknown origin have been reported. Physical therapy may increase the duration of pain or cause limitation of motion. Pain and anxiety may occur during the rehabilitation of patients with burns. Both morning stiffness and bone erosion have been reported in the physical therapy literature although causality is unclear. Erectile dysfunction has also been reported. Physical therapy has been used in pregnancy, specifically to treat women with pelvic girdle pain during pregnancy and at 3, 6, and 12 months postpartum. Reports of major adverse effects are lacking the available literature, but caution is advised nonetheless. All therapies during pregnancy and breastfeeding should be discussed with a licensed obstetrician/gynecologist before initiation.
Propolis: There is preliminary evidence that propolis may reduce dental pain, for example with the use of a propolis gel. Additional research is needed to before a firm conclusion can be made.
Avoid if allergic or hypersensitive to propolis, black poplar (Populas nigra), poplar bud, bee stings, bee products, honey, or Balsam of Peru. Severe allergic reactions have been reported. There has been one report of kidney failure with the ingestion of propolis that improved upon discontinuing therapy, and deteriorated with re-exposure. Avoid if pregnant or breastfeeding because of the high alcohol content in some products.
Psychotherapy: Psychotherapy may reduce pain, including chronic pain and pain associated with pelvic congestion. In some cases, psychotherapy and medication may be more effective. More research needs to be done in this area.
Psychotherapy cannot always fix mental or emotional conditions. Psychiatric drugs are sometimes needed. In some cases symptoms may get worse if the proper medication is not taken. Not all therapists are qualified to work with all problems. Use cautiously with serious mental illness or some medical conditions because some forms of psychotherapy may stir up strong emotional feelings and expression. Psychotherapy may help with post-partum depression, but is not a substitute for medication that may be needed in severe cases.
Qi gong: Preliminary research reports that internal Qi gong or externally applied Qi may be useful in the management of pain and anxiety caused by pain. However, the available research is low quality, and more evidence is needed in this area before a scientifically based conclusion can be drawn.
Qi gong is generally considered to be safe in most people when learned from a qualified instructor. Use cautiously with psychiatric disorders. In cases of potentially serious conditions, Qi gong should not be used as the only treatment instead of more proven therapies, and should not delay the time it takes to see an appropriate healthcare provider.
Reiki: Patients in a preliminary ("phase II") trial of Reiki in combination with standard pain medications (with opioids) were reported to experience improved pain control. Further research is needed to confirm these findings.
Reiki is not recommended as the sole treatment approach for potentially serious medical conditions, and should not delay the time it takes to consult with a healthcare professional or receive established therapies. Use cautiously with psychiatric illnesses.
Reishi mushroom: Reishi extract was effective in decreasing post-herpetic pain (pain after herpes lesions heal) in one case series. Further research is needed to confirm these results.
Avoid if allergic or hypersensitive to any constituents of Ganoderma lucidum or any member of its family. Use cautiously with diabetes, blood disorders (including hemophilia), low blood pressure or ulcers. Avoid if pregnant or breastfeeding.
Relaxation therapy: Most studies of relaxation for pain, including post-operative pain and low back pain, are poor quality and report conflicting results. Better research is necessary concerning the use of relaxation therapy either alone or as an addition to other treatments for acute or chronic pain.
Avoid with psychiatric disorders such as schizophrenia/psychosis. Jacobson relaxation (flexing specific muscles, holding that position, then relaxing the muscles) should be used cautiously with illnesses like heart disease, high blood pressure, or musculoskeletal injury. Relaxation therapy is not recommended as the sole treatment approach for potentially serious medical conditions and should not delay the time to diagnosis or treatment with more proven techniques.
Shark cartilage: Based on laboratory studies, shark cartilage may reduce inflammation. However, it is unclear if shark cartilage is a safe or helpful treatment for pain in humans.
Avoid if allergic to shark cartilage or any of its ingredients (including chondroitin sulfate and glucosamine). Use cautiously with sulfur allergy. Avoid if history of heart attack, vascular disease, heart rhythm abnormalities (arrhythmias), or heart disease. Use cautiously if history of liver or kidney disorders, tendency to form kidney stones, breast cancer, prostate cancer, multiple myeloma, breathing disorders (like asthma), cancers that raise calcium levels (breast, prostate, multiple myeloma or squamous cell lung cancer), and diabetes. Avoid if pregnant or breastfeeding.
TENS (transcutaneous electrical nerve stimulation): Auricular (ear) TENS (transcutaneous electrical nerve stimulation) is sometimes used in Europe to reduce the need for anesthesia during surgical procedures. There are multiple controlled studies of TENS for pain following various types of surgery, including abdominal surgery, lung surgery, gynecologic surgery, and orthopedic surgery. However, research is inconsistent and there is not enough reliable evidence to draw a firm conclusion in this area.
More research is needed to determine whether TENS can effectively pain associated with burns, cancer, broken bones or trauma.
The effect of TENS on chronic pain of various causes and locations remains controversial, and multiple controlled trials have been published in this area. Although numerous studies report benefits, studies have overall been small, poorly designed, and without clear descriptions of results. Better-designed research is needed before a firm conclusion can be reached.
TENS has been tested for its effects on pain control during lithotripsy (a technique used to break up gallstones). Currently, there is not enough reliable evidence to draw a firm conclusion in this area.
Avoid with implantable devices such as defibrillators, pacemakers, intravenous infusion pumps, or hepatic artery infusion pumps. Use cautiously with decreased sensation, like neuropathy, and with seizure disorders. Avoid if pregnant or breastfeeding.
Turmeric: Laboratory and animal studies show anti-inflammatory activity of turmeric and its constituent curcumin. Reliable human research is lacking.
Avoid if allergic or hypersensitive to turmeric (curcumin), yellow food colorings, or plants belonging to the Curcuma and Zingiberaceae (ginger) families. Use cautiously with a history of bleeding disorders, immune system deficiencies, liver disease, or gallstones. Use cautiously with blood-thinners like warfarin (Coumadin?). Use cautiously if pregnant or breastfeeding.
White horehound: White horehound has traditionally been used for pain and spasms from menstruation or intestinal conditions. There are no reliable human studies on safety or effectiveness for this use.
Avoid if allergic or hypersensitive to white horehound or any member of the Lamiaceaefamily (mint family). White horehound is generally considered safe when used to flavor foods. Use cautiously with diabetes, high/low/unstable blood pressure, high levels of sodium in the blood, irregular heartbeats, or gastrointestinal disease (such as ileus, atony, or obstruction). Use cautiously with diuretics (drugs that increase urine production). Avoid if pregnant or breastfeeding.

Side effects

General: Celebrex? has recently been linked to an increased risk of serious heart-related side effects, including heart attack and stroke. Selective COX-2 inhibitors have also shown to increase the risk of stomach bleeding, which can be life threatening. It appears that these risks also apply to traditional NSAIDs as well. Therefore, the U. S. Food and Drug Administration (FDA) requires that all NSAIDs, including COX-2 inhibitors, print serious warning labels that highlights the risk of potential heart problems and stomach bleeding. The labels must also state that patients who have recently had heart surgery should not take NSAIDs.
Fluid retention: COX-2 inhibitors may cause fluid retention (retaining water in the body) and swelling. Fluid retention can be a serious problem in patients who have high blood pressure or heart failure.
Stomach ulcers that bleed: The risk of developing stomach ulcers that bleed increases the longer the drug is taken. However, stomach ulcers can also develop suddenly. Patients are advised to stop taking medication and consult their healthcare providers if they experience a burning stomach pain, black bowel movements that look like tar, or vomit that contains blood or looks like coffee grounds.
Kidney problems: COX-2 inhibitors can cause kidney problems, including sudden kidney failure. Patients who have existing kidney problems may experience a worsening of symptoms.
Liver damage: COX-2 inhibitors may cause liver damage. Symptoms of liver damage include nausea, vomiting, tiredness, loss of appetite, itching, jaundice (yellow skin or eyes), flu-like symptoms and dark urine. Patients who experience such symptoms should consult their qualified healthcare providers.
Other: Other common but less severe symptoms include headache, indigestion, upper respiratory tract infection, diarrhea, sinus inflammation, stomach pain, and nausea.

Function

The cyclooxygenase (COX) enzymes are responsible for producing prostaglandins, which are biological mediators that cause inflammation. COX-1 enzymes protect the stomach lining from harsh acids and digestive chemicals and helps maintain kidney function. The body produces COX-2 enzymes when the joints are injured or inflamed.
COX-2 inhibitors, such as celecoxib (Celebrex?), only target the COX-2 enzyme that stimulates inflammation. Since these medications do not block the actions of the COX-1 enzyme, these medications generally do not cause the kind of stomach upset that is often associated with traditional nonsteroidal anti-inflammatory drugs (NSAIDs).
However, some studies have not shown any difference between the incidence of gastrointestinal side effects from traditional NSAIDs and COX-2 inhibitors. Also, COX-2 inhibitors do not offer the same kind of protection against heart disease as traditional NSAIDs. COX-2 inhibitors are often prescribed for long-term conditions, such as arthritis, because they may be safer for the stomach than traditional NSAIDs.

Preparations

Celecoxib (Celebrex?): Celecoxib (Celebrex?) is currently the only U.S. Food and Drug Administration (FDA) approved COX-2 inhibitor. However, the FDA is currently evaluating several studies, including long-term studies conducted by the National Institutes of Health (NIH), which suggest that the risk of cardiovascular events (such as heart attack and stroke) may be increased in patients taking Celebrex?.
Rofecoxib (Vioxx?): On September 27, 2004 rofecoxib (Vioxx?) was voluntarily withdrawn from the market due to an increased risk of heart attack and stroke. Currently, it is unclear whether this side effect occurs with other COX-2 inhibitors as well, or if it is specific to Vioxx?. When the medication was withdrawn, Vioxx? was one of the most widely used medications in the world.
Valdecoxib (Bextra?): On April 7, 2005, Pfizer agreed to suspend sales and marketing of Bextra? in the United States, pending further discussions with the FDA.

Uses

Selective COX-2 inhibitors are used to relieve pain and reduce inflammation. They are commonly used to relieve symptoms of osteoarthritis (type of arthritis that causes the cartilage to deteriorate), rheumatoid arthritis (autoimmune disorder that causes pain and inflammation of the joints), as well as to manage sudden pain in adults (such as short-term pain after a dental or surgical operation) and to treat painful menstruation cycles. They have also been used to reduce the number of colorectal polyps (abnormal growths in the colon and rectum) in patients who have familial adenomatous polyposis (FAP). Celebrex? is typically used along with the usual treatment for FAP patients.

Precautions

Avoid in patients who have had an allergic-type reaction to sulfa medicines because these patients are likely to experience an allergic reaction to selective COX-2 inhibitors as well.
Avoid in patients who have experienced asthma, hives, or allergic-type reactions after taking aspirin or other NSAIDs.
Avoid in patients who have heart problems (such as high blood pressure) and in those who recently had heart surgery because they have an even higher risk of experiencing heart problems, such as heart attack or stroke.
Avoid in patients with kidney or liver disease because selective COX-2 inhibitors may worsen their symptoms.
Avoid if pregnant or breastfeeding because the drug can crossover to the placenta or enter breast milk and potentially cause side effects in the fetus or infant.
Patients should tell their healthcare providers if they are taking any drugs (prescription or over-the-counter), herbs, or supplements because they can potentially interact with COX-2 inhibitors. COX-2 inhibitors are known to interact with ACE inhibitors (blood pressure medications) such as enalapril (Vasotec? or Renitec?), ramipril (Altace?, Tritace?, Ramace?, or Ramiwin?), furosemide (Lasix?, fluconazole (Diflucan?), ketoconazole (Nizoral?), phenytoin (Dilantin?), warfarin (Coumadin?), and aspirin (Bayer? or Excedrin?).