One of the most common sensations known to humanity is also one of the least understood. Throughout history, pain has been recognized as one of the strongest physical, emotional, and psychological motivators. Pain, of the avoidance thereof, motivates every living entity in some way—from the smallest single-cell organizes to the human race.

The 1979 International Association for the Study of Pain defined pain as “an unpleasant sensory and emotional experience associated with actual or potential tissue damage, or described in terms of such damage.” Dental pain has traditionally held a certain degree of foreboding in all known historical civilizations. This article presents COX-2 inhibitors as an option available to dentists for the treatment of acute and chronic pain, including the pain associated with temporomandibular joint disorders (TMD).

Dentists are often called upon to address mild, moderate, and severe levels of pain in both an acute and chronic nature from numerous etiologies. One of the most efficacious and widely used methods of treatment is nonsteroidal anti-inflammatory drugs (NSAIDs). These drugs are used by millions of patients each year for pain relief and control of inflammation in association with a wide variety of clinical conditions—including those of dental origin.

Evidence suggests that these agents—while widely used—are often associated with significant toxicities and adverse effects, especially in high-risk patients. Common side effects associated with NSAIDs include epigastric discomfort, dyspepsia, and nausea.¹ Serious gastrointestinal (GI) toxicity, such as bleeding, ulceration, and perforation of the stomach, small intestine, or large intestine, can occur at any time, with or without warning symptoms, in patients treated with NSAIDs. The relative risk of GI bleeding among NSAIDS users is greater in patients with a history of peptic ulcer disease or GI bleeding, those who use high doses of NSAIDs, and those over the age of 60. While the incidence of serious GI disturbances appears to be both agent and dose related, noticeable variability within any given patient population exists.^2-4 Although these effects may initially appear insignificant in select patients, they may eventually result in life-threatening conditions.

Regardless of their chemical classification, the primary mechanism of most NSAIDs is the inhibition of the cyclo-oxygenase enzyme that is responsible for the synthesis of prostaglandins.⁵ Prostaglandins exert various physiological effects into the tissues in which they are produced. While commonly addressed as mediators of inflammation, prostaglandins also facilitate cytoprotection of the GI tract, maintenance of renal blood flow, electrolyte balance, and stimulation of platelet aggregation and adhesion.⁶

The widespread use of NSAIDs (by prescription and over-the-counter) has caused the clinician to become aware of these potentially damaging effects when considering treatment options. As a result of the burgeoning number of patients who suffer from complications that may prohibit the application of traditional NSAIDs, a new family of cyclo-oxygenase-2 (COX-2) inhibitors has been developed. While COX-2 inhibitors are believed to prevent prostaglandin synthesis by restricting the production of COX-2, they do not restrain the cyclo-oxygenase-1 (COX-1) isoenzyme that controls cytoprotective prostaglandins within the stomach.⁷

Clinical trials indicate that rofecoxib is safe when used as directed, with no effect on bleeding time or platelet aggregation (Tables 1 and 2). Studies also indicated that rofecoxib has been associated with a significantly lower percentage of patients with duodenal ulcers as viewed by 6-month endoscopy, with a cumulative incidence of serious upper GI events (0 months to 1 year) of less than 0.2% (Table 3).

Table 1

Rofecoxib: Effect on Bleeding Time in Healthy Volunteers*

• No effect on bleeding time when doses of rofecoxib of up to 375 mg were administered daily for up to 12 days.
• No effect on bleeding time with single doses of 500 mg or 1000 mg of rofecoxib.

*Results based on studies performed and presented by Mereck & Co, Inc, Whitehouse Station, NJ

Table 2

Rofecoxib: Effect on Platelet Function in Healthy Volunteers*

• Rofecoxib 50 mg had no effect on platelet aggregation.
• At steady state, rofecoxib 50 mg once daily had no effect on the antiplatelet activity of low-dose aspirin (81 mg once daily).
• Rofecoxib is not a substitute for aspirin for cardiovascular prophylaxis.
• Concomitant administration of low-dose aspirin with rofecoxib may result in an increased risk of GI ulceration or other complications compared with use of rofecoxib alone.

*Results based on studies performed and presented by Mereck & Co, Inc, Whitehouse Station, NJ

Table 3

Rofecoxib: Cumulative Incidence of Serious Clinical Upper GI Events in 3,357 Patients Treated with Rofecoxib*

Obstruction and Significant Bleeds

0-3 Months                             0-12 Months

Number of Patients (%)          Number of Patients (%)

2 (0.06%)                                4 (0.12%)

Approximately 23% of these 3,357 patients participated in studies that required them to be free of ulcers at study entry. It is unclear if this study population is representative of the general population

*Results based on studies performed and presented by Mereck & Co, Inc, Whitehouse Station, NJ

Like all NSAIDs, selective COX-2 inhibitors must be used according to their prescribing information. The prescribing information for rofecoxib states that the long-term administration of NSAIDs has resulted in renal papillary necrosis and other renal injury.⁸ Renal toxicity has also been seen in patients in whom renal prostaglandins have a compensatory role in the maintenance of renal perfusion. In these patients, administration of a NSAID may cause a dose-dependant reduction in prostaglandin formation and, secondarily, in renal blood flow, which may precipitate overt renal decompensation. Patients at greatest risk of this reaction are those with impaired renal function, heart failure, liver dysfunction, those taking diuretics and ACE inhibitors, and the elderly. Discontinuation of NSAID therapy is usually followed by recovery to the pretreatment state. Clinical trials with rofecoxib at daily doses of 12.5 mg and 25 mg have demonstrated renal effects (eg, hypertension, edema) similar to those observed with comparator NSAIDs.⁸ These effects occurred with an increased frequency with chronic use of rofecoxib at doses above the 12.5 to 25 mg range. Caution should be employed with initiating treatment with rofecoxib in patients with considerable dehydration. It is advisable to rehydrate patients first and then start therapy with rofecoxib. Caution is also recommend in patients with pre-existing kidney disease.⁸

Acute Dental Pain

Rofecoxib is indicated for the treatment of acute pain. In a single-dose study of patients with postoperative dental pain, rofecoxib 50 mg demonstrated pain relief generally similar to ibuprofen 400 mg, the maximum dose of ibuprofen for analgesia (Figure). Patients in this study had a minimum of two third molars removed with at least one molar partially embedded in bone with mandibular impaction. Patients experienced moderate-to-severe pain following the procedure. Rofecoxib is dosed once-daily as needed. For analgesia, ibuprofen 400 mg can be dosed every four to six hours.

A parallel-group evaluation of rofecoxib (50 mg) and celecoxib (200 mg) was recently performed to compare the analgesic efficacy of the COX-2 inhibitors with ibuprofen (400 mg) and placebo in patients with postoperative dental pain.⁹ Pain intensity, pain relief, and global evaluations were recorded during the 24-hour post-dosage period to facilitate evaluation of the overall analgesic effect, onset of action, peak effect, and duration of effect for the various medications. The results of this evaluation indicated that rofecoxib demonstrated a superior analgesic effect compared to celecoxib on all measures of analgesic efficacy.

Chronic Pain

Treatment of Temporomandibular Disorder

The literature has discussed persistent symptoms of orofacial pain disorders and has indicated that approximately 7% (13 million) of Americans suffer from an orofacial disorder that causes pain in the face or jaw. ^10,11 As the dental profession gradually evolved into a true specialty of medicine, its procedures became specialized and separated into the current concentrations recognized by the American Dental Association. The maturation of the dental profession and the current extension of diagnostic treatment modalities into the treatment of temporomandibular joint (TMJ) disorders have caused clinicians to place increased emphasis on pain control beyond the borders of the teeth and periodontium. Evaluations of clinical populations indicate that a smaller percentage of these patients have severe enough problems to seek care for TMJ disorders.¹² This prevalence coupled with the potential personal and societal impact of chronic orofacial pain disorders warrant understanding by all health professionals.

Clinical diagnosis of TMDs is generally made using signs and symptoms that are characteristic of each disorder. In addition to muscle and joint pain during palpitation, the most common signs include joint noise, painful limitation, and/or deviation in the mandible’s range of motion. General symptoms and difficulty in jaw function (eg, mastication).^13-17 The reduction or elimination of pain and restoration of normal jaw function are the primary objectives of treatment (Table 4). In each of these disorders, repetitive strain to the muscles and joints from oral habits, trauma (direct and indirect), or joint laxity are often underlying factors that contribute to their development.

Table 4

Common TMD Subtype Diagnoses and Their Characteristics

Masticatory Muscle Disorders

Myofascial Pain: Regional pain associated with tender points in firm bands of skeletal muscles, tendons, or ligaments.

Postexercise myalgia: Tender sore muscles that arise following significant exercise or use of a muscle that is deconditioned.

Myositis: Acute muscle pain with inflammation, generalized tenderness, and swelling from infection or trauma.

Muscle spasm: Acute muscle pain due to a brief involuntary tonic contraction from overstretching or overuse of a muscle.

Muscle contracture: Gross shortening and fibrosis of a muscle from trauma, infection, or prolonged hypermobility.

Fibromyalgia/Chronic fatigue syndrome: A chronic muscle pain with widespread pain and tenderness

Temporomandibular Joint Disorders

TMJ Capsulitis: Inflammation and tenderness of the joints from trauma or intrinsic joint disease.

Disk displacement with reduction: Reciprocal clicking of the TMJ on opening and closing, occasionally with intermittent locking.

A TMJ disk displacement without reduction: Limited mouth opening due to interference of condylar translation by the disc secondary to disc adhesion, deformation, or dystrophy.

TMJ dislocation or subluxation: Hypermobility of the joint due to laxity of the ligmanets.

Osteoarthritis (OA): Degenerative joint changes that case crepitus, jaw dysfunction, radiographic changes, pain, inflammation, and tenderness of the joint.

Polyarthritic disease: Systemic rheumatic disease that affects the TMJ including systemic osteoarthritis, rheumatoid arthritis, psoriasis, lupus erythematosus, scleroderma, Sjogren’s syndrome, and hyperuricemia.

Initial Treatment of TMDs

TMD symptoms may be resolved with pharmacological management and treatment with NSAIDs or COX-2 inhibitors. For this reason, the initial treatment of all TMDs should be designed to reduce pain and repetitive strain, encourage relaxation, and promote healing. Randomized clinical trials have suggested that short-term use of analgesic and/or anti-inflammatory medications should be considered with homecare.¹⁸ COX-2 inhibitors can be applied for long-term treatment with minimized GI toxicity and reduced renal and platelet side effects. Self-care includes the use of superficial heat, a pain-free diet with progression of the diet as tolerated, a hinge axis/rotation jaw exercise, and monitoring and control of oral habits (eg, clenching and bruxism, gum chewing, control of yawning) (Table 5).

Table 5

Initial Care for TMD Pain

Use anti-inflammatory medications: Over-the-counter ibuprofen or aspirin may be useful for short-term use, or prescription anti-inflammatories (eg, rofecoxib, 25 mg per day for pain and inflammation) can be used for more extended use to reduce gastrointestinal toxicity.

Apply moist heat or cold compresses: To the joint or muscles that are sore. Apply heat for 20 minutes 2 to 4 times daily. Microwave a wet towel for approximately 1 minute or until towel is warm. You can also wrap this moist hot towel around a hot water bottle to keep it warm longer. For cold compresses, use ice wrapped in a thin wash cloth for 10 minutes, 4 times daily. Ice should only be applied to the painful area until numbness is experienced. Heat or ice can reduce joint or muscle pain and relax the muscles.

Eat a softer diet: Avoid hard foods, such as French bread or bagels. Avoid chewy foods, such as steak or candy. Cut fruits into small pieces and steam vegetables. Chew with your back teeth rather than biting with your front teeth. DO NOT CHEW GUM.

Keep your tongue up and teeth apart: The teeth should never be touching (except occasionally during swallowing). We suggest that you closely monitor your jaw position during the day in order to maintain a relaxed and comfortable position. This involves placing the tongue lightly on top of your upper front teeth, allowing the teeth to come apart and relax the jaw muscles.

Avoid oral habits that put strain on the jaw muscles and joints: These include clenching, grinding (bruxism), touching, biting cheeks, tongue pushing against teeth, jaw tensing, biting objects, or other habits.

Avoid activities that involve wide or prolonged opening of the jaw (yawning, prolonged dental treatments, etc) until the pain has been reduced.

Avoid stomach sleeping or learning on the jaw since this puts adverse forces on the jaw and neck muscles.

Accordingly to our experience, rofecoxib has been successfully utilized to treat TMDs within the masticatory system, temporal tendinitis, stylomandibular ligaments, occipital neuralgia, and myofascial trigger points that occur as a result of direct or indirect (acceleration) trauma experienced in motor vehicle accidents. Treatment of acute and chronic inflammation found in various soft tissue injuries of the head and neck has been facilitated with a loading dose of rofecoxib 50 mg once daily followed by 12 mg to 25 mg per day.

Expand Treatment of TMD

When further treatment is indicated, a variety of additional approaches can be used (Table 6). Because of the low side effect profiles, COX-2 inhibitors should be considered for continued care when short-term relief of TMD pain is not obtained. In addition, other pharmacological approaches can be used for specific associated problems such as muscle relaxants to reduce anxiety, fear, and muscle tension, sedatives to enhance sleep, and antidepressants for pain, depression, and sleep enhancement.¹⁴ Treatment of more severe joint inflammatory symptoms can be achieved with corticosteroids in temporomandibular joint (TMJ) synovitis, either through oral dose packs, inontophoresis, or injections.^19,20 The steroid effect can be prolonged by the addition of COX-2 inhibitors for a few weeks following the completion of the dose pack. Iontophoresis of steroids into the TMJ has also been evaluated and found to be marginally effective in clinical trials. While injecting the TMJ with corticosteroids can provide more targeted anti-inflammatory effects, multiple injections are contraindicated since they have been associated with progression of degenerative joint disease.

Table 6

Management Options for Expanded Treatment of TMD When Initial Treatment Fails to Resolve the Pain

1. Pharmocotherapy
1. Anti-inflammatories
2. Narcotic Analgesics
3. Anesthetics
4. Muscle Relaxants
5. Tricyclics
6. Sedatives
2. Behavioral and Psychological Therapy
1. Behavior Modification and Habit Reversal
2. Biofeedback
3. Hypnosis
4. Counseling and Psychotherapy
3. Orthopedic Stabilization with Splints and Orthodontics
1. Stabilization Splint
2. Anterior Repositioning Splint
3. Anterior Bite Plane
4. Physical medicine
1. Exercises
2. Ultrasound
3. Ionophoresis
4. Electrical Stimulation
5. TMJ Surgery
1. Open
2. Arthroscopic

Physical medicine (eg, jaw exercises and modalities) can also be efficacious for treatment of TMD pain.²¹ Current research suggests that physical therapy exercises and modalities may provide a short term palliative effect in the reduction of TMD pain and/or an increased range of motion in the jaw. Treatment of TMD with physical therapy techniques follow the same orthopedic and physical therapy principles as with any musculoskeletal condition.

The use of an intraoral splint provides various levels of efficacy during treatment of TMD and bruxism.^18,22 The two most common splints used in clinical practice are the stabilization splint (SS) and anterior repositioning splint (ARS). While the latter is used to place the mandible and TMJ anteriorly and to reduce the TMJ reciprocal click, the SS provides a passive occlusal surface. Cognitive-behavioral approaches can also help change maladaptive behaviors that place strain on the masticatory system and cause TMD pain.²³ Biofeedback, relaxation techniques, and stress management can be used alone or in conjunction with the aforementioned procedures. These therapies help the patients be aware of and control clenching and grinding of the teeth.

Surgical intervention can be considered if comprehensive nonsurgical rehabilitation care has failed and the sensation of pain is persistent, localized to the TMJ, and associated with specific structural changes in the joint. Any concurrent muscle diagnoses and relevant contributing factors have been addressed and controlled. Refraining from surgery is appropriate since the effectiveness of nonsurgical care for advanced TMJ diagnoses is comparable with surgical interventions.²⁴ In general, less invasive surgeries; one should thus consider an arthrocentesis and/or arthroscopic procedure before a more invasive surgery such as diskectomy or disk repair procedure. Surgery should be followed with appropriate medications, physical therapy, and (where indicated) splint therapy, and/or continued intervention by the health psychologist for any persistent psychosocial or behavioral contributing factors.

Conclusion

Pain management options have significantly evolved throughout the years. Diagnosis of causative factors should be the clinician’s initial concern, closely followed by an analysis of treatment options. Application of anti-inflammatory agents, NSAIDs, and more recently, COX-2 inhibitors, has greatly augmented the clinician’s pain reduction armamentarium. The treatment and control of pain has been facilitated by the utilization of COX-2 inhibitors, with reduced concern of negative GI side effects. As treatment options are extensively tested through clinical trials, triaging patients to appropriate treatment strategies will result in increasingly predictable results. We should remind ourselves, however, that patients with similar diagnoses may have different contributing factors and results. In the more complex cases, addressing the causative web can be complex and requires the use of a team that includes a physical therapist and/or psychologist. Treatment of acute or chronic situations will require and increasingly unified approach that will allow the patient to be comprehensively evaluated and treated.

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