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
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).
Rofecoxib: Effect on
Bleeding Time in Healthy Volunteers*
effect on bleeding time when doses of rofecoxib of up to 375 mg were
administered daily for up to 12 days.
effect on bleeding time with single doses of 500 mg or 1000 mg of
*Results based on studies performed and presented by Mereck
& Co, Inc, Whitehouse Station, NJ
Rofecoxib: Effect on
Platelet Function in Healthy Volunteers*
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).
is not a substitute for aspirin for cardiovascular prophylaxis.
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
Incidence of Serious Clinical Upper GI Events in 3,357 Patients Treated with
0-3 Months 0-12 Months
Number of Patients (%) Number
of Patients (%)
2 (0.06%) 4
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
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.
(Continued from page 1 )
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
Common TMD Subtype
Diagnoses and Their Characteristics
Masticatory Muscle Disorders
Regional pain associated with tender points in firm bands of skeletal muscles,
tendons, or ligaments.
myalgia: Tender sore muscles that arise following significant exercise
or use of a muscle that is deconditioned.
Acute muscle pain with inflammation, generalized tenderness, and swelling from
infection or trauma.
Acute muscle pain due to a brief involuntary tonic contraction from
overstretching or overuse of a muscle.
Gross shortening and fibrosis of a muscle from trauma, infection, or prolonged
fatigue syndrome: A chronic muscle pain with widespread pain and
Temporomandibular Joint Disorders
TMJ Capsulitis: Inflammation
and tenderness of the joints from trauma or intrinsic joint disease.
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.
(OA): Degenerative joint changes that case crepitus, jaw dysfunction,
radiographic changes, pain, inflammation, and tenderness of the joint.
Systemic rheumatic disease that affects the TMJ including systemic
osteoarthritis, rheumatoid arthritis, psoriasis, lupus erythematosus,
scleroderma, Sjogren’s syndrome, and hyperuricemia.
Initial Treatment of
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).
Initial Care for TMD
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
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
Avoid activities that involve wide or prolonged opening
of the jaw (yawning, prolonged dental treatments, etc) until the pain has
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
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.
for Expanded Treatment of TMD When Initial Treatment Fails to Resolve the Pain
- Behavioral and Psychological Therapy
Modification and Habit Reversal
- Orthopedic Stabilization with Splints
- Physical medicine
- TMJ Surgery
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
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.
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
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