Pain Management

Need for Pain Control

Pain, as defined by the International Association for the Study of Pain, is "an unpleasant
sensory and emotional experience arising from actual or potential tissue damage or
described in terms of such damage." Fear of pain is a significant reason for many people to
avoid seeking dental care. No matter how successful or how deftly conducted, most dental
procedures produce tissue trauma and release potent mediators of inflammation and pain.

Pain is just one response to the trauma of surgery, however. In addition to the major stress of
surgical trauma and pain, the substances released from injured tissue evoke "stress
hormone" responses in the patient. Such responses promote breakdown of body tissue;
increase metabolic rate, blood clotting, and water retention; impair immune function; and
trigger a "fight or flight" alarm reaction with autonomic features (e.g., rapid pulse) and
negative emotions. Pain itself may lead to shallow breathing and cough suppression in an
attempt to "splint" the injured site followed by retained pulmonary secretions and pneumonia.
Unrelieved pain also may delay the return of normal gastric and bowel function in the
postoperative patient.

The physiological and psychosocial risks associated with untreated pain are greatest in frail
patients with other illnesses such as heart or lung disease, those undergoing major surgical
procedures such as aortic surgery, and the very young or very old. Because of advances in
surgical and anesthetic techniques, it is now common for such patients to undergo operations
once dismissed as prohibitively risky.

In the past, postoperative pain was thought to be inevitable, a harmless though intense
discomfort that the patient had to tolerate. Now we know that unrelieved pain after surgery or
trauma is often unhealthy; fortunately, it is preventable or controllable in an overwhelming
majority of cases. Patients have a right to treatment that includes prevention or adequate
relief of pain.

Undertreatment of pain is a significant problem. Numerous clinical surveys have shown that
postoperative pain is often inadequately treated because of undermedication, leaving
patients to suffer needlessly. Recognition of the widespread inadequacy of pain management
and the detrimental effects of untreated pain has led to corrective efforts in numerous health
care disciplines involved with pain management.

Health care is both a technical and an ethical enterprise. The ethical obligation to manage
pain and relieve the patient's suffering is at the core of health care professional's
commitment. While medical treatments often involve risks and burdens, anything harmful to
the patient, including postoperative pain, should be minimized or prevented if possible. The
ethical importance of pain management is further increased when additional benefits for the
patient are realized–earlier mobilization, shortened hospital stay, and reduced costs. If
inadequate pain management results from a clinician's conflict between reducing pain and
avoiding potential side effects and/or legal liability, achieving greater technical competence
and knowledge of risks and benefits can help to reduce such conflicts.
Pain Classification

Successful treatment of pain conditions with analgesics requires a basic understanding of the
types of pain. Painful conditions can be divided into two basic categories. Nociceptive pain is
a result of mechanical, thermal, or chemical activation of nociceptive afferent receptors.
Nociceptive pain may be either somatic or visceral. Somatic nociception involves pathology in
the skin, muscles, fascia, and bones and is well localized. An example is the pain associated
with cavity preparation or periodontitis. In both these conditions, inflammatory mediators may
sensitize and/or activate nociceptive receptors that result in transduction of the noxious
stimulus into an electrical signal. The electrical signal is then transported toward the brain for
interpretation. Visceral nociceptive pain is poorly localized, may be referred to superficial
somatic regions, and involves pathologic conditions in deep, visceral tissues. An example is
angina resulting from myocardial ischemia.

Neuropathic pain is a result of aberrant somatosensory activity either in the peripheral

nervous system or the central nervous system (CNS). It is frequently characterized by
paroxysmal shooting or electrical shocklike pains, often on a background of burning or
constricting sensation. Examples of neuropathic pain encountered in the orofacial region
include trigeminal neuralgia and postherpetic neuralgia.

Pain may also be characterized as acute or chronic. Acute pain frequently has a known
cause, usually subsides as healing takes place, and has a predictable endpoint. Acute pain is
associated with anxiety and the physiologic "flight or fight" responses of increased pulse and
respiratory rate. Chronic pain is of greater than 3 to 6 months duration. Patients with chronic
pain do not usually manifest the physiologic arousal seen with acute pain because the body
has adapted to the pain state. However, they may exhibit reactive depression and decreased
function.

Pain Assessment

Pain is a complex, subjective response with several quantifiable features, including intensity,
time course, quality, impact, and personal meaning. The reporting of pain is a social
transaction between caregiver and patient. Therefore, successful assessment and control of
postoperative pain depends in part on establishing a positive relationship between health
care providers, patients, and (when appropriate) their families. Studies have shown that the
patients provided with information related to physiological coping (instruction in coughing,
deep breathing, turning, and ambulation) reported less pain, were given fewer analgesics
postoperatively and had shorter lengths of stay.

Patients should be informed that pain relief is an important part of their health care. Pain is a
subjective phenomenon. As such, the care provider must accept that the patient's self-report
is the single most accurate and reliable indicator of the existence and intensity of pain and
any resultant distress. This orientation is reflected in a commonly cited definition of pain: Pain
is whatever the experiencing person says it is and exists whenever he says it does. Self-
report measurement tools such as adjective or numerical rating scales or visual analogue
scales can assist the patient in quantifying and characterizing the pain.
In practical use, the visual analog scale is always presented graphically, usually with a 10-cm
baseline and endpoint adjective descriptors. Patients place a mark on the line at a point that
best represents their pain. The visual analog scale is scored by measuring the distance of
patient's mark from the zero. For example, numerical rating scales are sometimes presented
verbally, and adjective rating scales are presented as a list of pain descriptors. In a graphic
format, scoring of the numerical and adjective rating scales may be the same as that
described above for the visual analog scale, or they can be scored as numeric integers.

For each of these scales the clinician should request the patient's self-report, not only with
the patient at rest but also during routine activity such as coughing, deep breathing, or
moving (e.g., turning in bed). Complaints of pain must be heeded. The patient should be
observed for behaviors that often indicate pain, such as splinting the operative site, distorted
posture, impaired mobility, insomnia, anxiety, attention seeking, and depression. Patient
awareness of pain and the ability to control pain are important components of pain
assessment. If pain behavior is observed or if the patient expresses feelings of inadequate
control, a member of the health care team should discuss these with the patient and share
this information with other members of the team. The pain management plan should then be
revised as needed.

The clinician should document the patient's preferred tool for pain assessment and the goal
for postoperative pain control as expressed by a score on a pain scale in the patient's chart
as part of the pain history. Simply to record patient responses to the questions "how is your
pain?" invites misunderstanding or denial and hinders quantification. Pain should be
assessed and documented: 1) preoperatively; 2) routinely at regular intervals postoperatively,
as determined by the operation and severity of the pain (e.g., every 2 hours while awake for 1
day after surgery); 3) with each new report of pain; and 4) at a suitable interval after each
analgesic intervention (e.g., 30 minutes after parenteral drug therapy and 1 hour after oral
analgesics). Most important, the team should evaluate immediately each instance of
unexpected intense pain, particularly if sudden or associated with oliguria or altered vital
signs such as hypotension, tachycardia, or fever, and consider new diagnoses such as
wound dehiscence, infection, or deep venous thrombosis.

Occasionally, apparent discrepancies between behaviors and a patient's self-report of pain

may occur. For example, patients may describe pain as an 8 out of 10 on a pain scale while
smiling and walking freely or as 2 out of 10 while tachycardic, splinting, and sweating.
Discrepancies between behavior and a patient's self-report may result from excellent coping
skills. The patient who uses distraction and relaxation techniques may engage in diversionary
activities while still experiencing severe pain. Patients may deny severe pain for a variety of
reasons, including fear of inadequate pain control or perception that stoicism is expected or
rewarded. Similarly, patients managed with as-needed analgesia may perceive that
medication will be given only if the pain score is very high. Patients who perceive staff as
inattentive to their concerns may use pain as a way to get help for other reasons.

When discussing pain assessment and control with patients, members of the health care
team should emphasize the importance of a factual report, thereby avoiding both stoicism
and exaggeration. Patients with anxiety or other concerns should rate their mood and
emotional distress separately from their pain by using similar scales. When discrepancies
between behaviors and self-report of pain occur, clinicians should address these differences
with the patient. The team and the patient should then renegotiate the pain management
plan.
Patients unable to communicate effectively with staff require special consideration for pain
assessment, e.g., neonates and children, developmentally delayed persons, psychotic
patients, patient with dementia, and non-English speaking patients. Children and cognitively
impaired patients require simpler or modified pain measurement scales and assessment
approaches. The staff should work with both the patient and parent or guardian pre- and
postoperatively. Staff should endeavor to find a translator for the non-English speaking
patient, at least once, to determine a convenient way to assess pain. Members of the health
care team should attend to the preferences and needs of patients whose education or
cultural tradition may impede effective communication. Certain cultures have strong beliefs
about pain and its management, and these patients may hesitate to complain about
unrelieved pain. Such beliefs and preferences should be determined and respected, if at all
possible.

Misconceptions About Pain and Analgesics

A significant barrier to the effective use of analgesics in managing pain involves several
misconceptions regarding pain and its control held by both patients and health care provides.

Misconception 1- Patients who are in pain always have observable signs. Although many
patients in acute pain exhibit evidence of anxiety, distress, decreased function, many do not.
Such overt pain behaviors also may not be seen at all in patients attempting to adapt to, and
cope with, persistent pain. It is important to remember that, to treat the pain effectively, the
clinician must first believe the patient's complaint of pain.

Misconception 2- Obvious pathology, test results, and/or the type of surgery determine the
existence and the intensity of pain. Although the ability to identify a pathologic process
underlying a patient's pain complaint is a key element in planning and initiating definitive
treatment, failure to identify the source of a patient's pain does not necessarily mean that it
does not exist.

Misconceptions 3- Patients should wait as long as possible before taking a pain medication.
This abstinence will teach them to have a better tolerance for pain. Pain that is untreated
often escalates. Without treatment, sensory input from injured tissue reaches spinal cord
neurons and causes subsequent responses to be enhanced. Pain receptors in the periphery
also become more sensitive after injury. Studies have demonstrated long-lasting changes in
cells within the spinal cord pain pathways after brief painful stimuli. These physiologic studies
confirm long-standing clinical impressions that established pain is more difficult to suppress.
Aggressive pain prevention and control that occurs before, during, and after a painful event
such as dental surgery can yield both short- and long-term benefits. Prevention of pain often
requires a lower analgesic dose than does treatment. This lower dose can also result in
decreased side effects. Patients should be encouraged to use analgesics before pain
becomes severe and difficult to control.

Pharmacologic Management

Pharmacologic management of mild to moderate postoperative pain should begin unless

there is a contraindication with an NSAID. Moderately severe to severe pain normally should
be treated initially with an opioid analgesic. After many relatively noninvasive surgical
procedure, NSAIDs alone can achieve excellent pain control.
NSAIDs decrease levels of inflammatory mediators generated at the site of tissue injury.
Even when insufficient alone to control pain, NSAIDs have a significant opioid dose-sparing
effect upon postoperative pain and can be useful in reducing opioid side effects. The
concurrent use of opioids and NSAIDs often provides more effective analgesia than either of
the drug classes alone. Although it is likely that NSAIDs also act within the central nervous
system, in contrast to opioids they do not cause sedation or respiratory depression, nor do
they interfere with bowel or bladder function. Acetaminophen does not affect platelet
aggregation, nor does it provide peripheral antiinflammatory activity. Some evidence exists
that two salicylates do not affect platelet aggregation profoundly; these are salsalate and
choline magnesium trisalicylate. All other NSAIDs appear to produce a risk of platelet
dysfunction that may impair blood clotting and carry a small risk of gastrointestinal bleeding.

Opioid analgesics are the cornerstone of pharmacological postoperative pain management,

especially for more extensive surgical procedures that cause moderate to severe pain. Other
agents such as NSAIDs or single injections of local anesthetics may control mild to moderate
pain after relatively minor procedures or reduce opioid dose requirements after more
extensive operations when this is a goal. Even in the absence of preemptive efforts targeted
at postoperative analgesia adequate postoperative pain control can usually be achieved with
opioid analgesics. When increasing doses of opioids are ineffective in controlling
postoperative pain a prompt search for residual pathology is indicated and other diagnoses
such as neuropathic pain should be considered.

Opioid tolerance or physiological dependence is unusual in short-term postoperative use in

opioid naive patients. Likewise, psychologic dependence and addiction are extremely unlikely
to develop after patients without prior drug abuse histories use opioids for acute pain. Proper
use of opioids involves selecting a particular drug and route of administration and judging: 1)
suitable initial dose; 2) frequency of administration; 3) optimal doses of nonopioid analgesics,
if these are also to be given; 4) incidence and severity of side effects; and 5) whether the
analgesic will be given in an inpatient or ambulatory setting. Titration to achieve the desired
therapeutic effect in the immediate postoperative period and to maintain that effect over time
should be emphasized.

Mechanics of Action

Opioids produce analgesia by binding to opioid receptors both within and outside the central
nervous system. Opioid analgesics are classified as full agonists, partial agonists, or mixed
agonist-antagonists depending on the manner in which they interact with opioid receptors.
Full agonists produce a maximal response within the cells to which they bind; partial agonists
produce a lesser response, regardless of their concentration; and mixed agonist-antagonists
activate one type of opioid receptor while simultaneously blocking another type.

Several types and subtypes of such receptors exist. The most important receptor type for
clinical analgesia is named "mu" because of its affinity for morphine. Other commonly used
mu opioid agonists include hydromorphone, codeine, oxycodone and hydrocodone,
methadone, levorphanol, and fentanyl. All mu opioid agonists have the potential to cause
constipation, urinary retention, sedation, and respiratory depression and frequently also
produce nausea or confusion. Mixed agonist antagonists in clinical use include pentazocine
[Talwin], butorphanol tartrate [Stadol], and nalbuphine hydrochloride [Nubain]; each of these
blocks is neutral at the mu opioid receptor while simultaneously activating a different type of
opioid receptor termed "kappa.' Patients receiving mu opioid agonists should not be given a
mixed agonist-antagonist because doing so may precipitate a withdrawal syndrome and
increase pain. Mixed agonist-antagonists and partial agonists may exhibit a ceiling effect not
only with respect to respiratory depression but also in regard to their analgesic activity. In the
awake patient, there is a clinical ceiling analgesic effect even with morphine because side
effects such as respiratory depression limit the dose that may be safely given. However, this
does not limit the ability of clinicians to effectively increase the drug dose when the painful
stimulus increases and respiratory status is monitored.

Meperidine [Demerol], a mu opioid analgesic, is commonly used for postoperative pain

control. Meperidine is commonly underdosed and administered too infrequently even by
physicians aware of its pharmacokinetics. The common postoperative meperidine order of 75
mg parenterally every 4 hours as needed often is inadequate for several reasons. Meperidine
produces clinical analgesia for only 2.5-3.5 hours, and a dose of 75 mg every 4 hours is
equivalent to only 5-7.5 mg of morphine. Therefore, to obtain postoperative analgesia equal
to that from 10 mg of morphine sulfate every 4 hours, a clinician would have to use 100-150
mg of meperidine every 3 hours.

Because of its unique toxicity, meperidine is often contraindicated in patients with impaired
renal function and those receiving antidepressants of the monamine oxidase inhibitor class.
Normeperidine (6-N-desmethylmeperidine) is a toxic meperidine metabolite excreted through
the kidney. In patients with normal renal function, normeperidine has a half-life of 15 to 20
hours; this time is extended greatly in elderly individuals and patients with impaired renal
function. Normeperidine is a cerebral irritant that can cause effects ranging from dysphoria
and irritable mood to convulsions. These effects have been observed even in young,
otherwise healthy patients given sufficiently high doses of normeperidine postoperatively.
Therefore, meperidine should be reserved for very brief courses in otherwise healthy patients
who have demonstrated an unusual reaction (e.g., local histamine release at the infusion
site) or allergic response during treatment with other opioids such as morphine or
hydromorphone.

Dosage and Frequency

Titration of opioids should be based on the patient's analgesic response and side effects.
Remember that patients vary greatly in their analgesic dose requirements and responses to
opioid analgesics. Relative potency estimates provide a rational basis for selecting the
appropriate starting dose to initiate analgesic therapy, changing the route of administration
(e.g., from parenteral to oral), or when switching to another opioid. Dosage conversion
factors based on relative potency estimates may differ somewhat between individual patients.
When estimating the initial postoperative dose of an opioid analgesic, a clinician should
consider whether patients have been receiving opioid analgesics preoperatively. In such
patients, supplemental postoperative doses should be adjusted above the preoperative
baseline requirement unless the operation itself is likely to remove the painful stimulus.

An "as-needed" order for opioid administration can result in prolonged delays while the nurse
unlocks the controlled substances cabinet and prepares the drug for administration and until
the drug takes effect. These delays can be eliminated by administering analgesics on a
regular time schedule initially. For example, if the patient is likely to have pain requiring opioid
analgesics for 48 hours following surgery, morphine could be ordered every 4 hours by the
clock (not "as needed") for 36 hours. Once the duration of analgesic action is determined for
a patient, the dosage frequency should be adjusted to prevent pain from recurring.
Depending on patient preferences, the orders may be written so that the patient can refuse
an analgesic if not in pain or forego it if asleep. However, as in dosing with other drugs that
require a steady blood level to remain effective, interruption of an around-the-clock dosage
schedule during the hours of sleep may cause the patient to be suddenly awakened by
intense pain as blood analgesic levels decline.

It may be acceptable late in the postoperative course to give the same drug every 4 hours as
requested. Switching from an around-the-clock to an as-needed dosage schedule later in the
patient's course is one way to provide pain relief while minimizing the risk of adverse effects
as the patient's analgesic dose requirement diminishes. As part of this schedule, a patient's
pain should be assessed at regular intervals to determine the efficacy of the drug
intervention, the presence of side effects, or the need for dosage adjustment or supplemental
doses for breakthrough pain. Effective use of opioid analgesics should facilitate routine
postoperative activities—e.g., coughing and deep breathing exercises, ambulation, and
physical therapy. The opioid should be withheld if the patient is sedated when awake or
whenever there is respiratory depression (usually fewer than 10 breaths per minute).

Routes of Administration

Opioids may be administered by a variety of routes; oral dosing is usually the most
convenient and least expensive route of administration. It is appropriate as soon as the
patient can tolerate oral intake and is the mainstay of pain management in the ambulatory
surgical population.

Preoperative intravenous or epidural access may be appropriate for postoperative

management of severe pain, even when the oral route is available. Relatively few side effects
will occur ordinarily, providing that these modalities are carefully managed by clinicians with
appropriate expertise. Using potent analgesics or invasive techniques postoperatively, at a
time when the patient's level of consciousness and physical function are returning to normal,
requires careful titration and patient assessment.

Drug dosage, frequency, side effects, and risks differ even more noticeably between the
intravenous and epidural routes than between the oral and intravenous routes. Clinicians not
familiar with epidural opioid doses and pharmacokinetics must review the literature carefully
before using that route. In addition, side effects (e.g., confusion, respiratory depression,
hypotension, urinary retention, or pruritus) associated with opioids can be greater with
intravenous and epidural administration and require ongoing assessment and monitoring.
Other potential problems that dictate expert vigilance and follow-up during epidural analgesia
include abscess development or anesthesia of a nerve root at the site of catheter tip. These
routes of administration are best limited to specially trained staff who are knowledgeable and
skilled in the management of patients receiving intravenous or epidural opioids typically
under the direction of an acute or postoperative pain treatment service.

Patient controlled analgesia is a safe method for postoperative pain management that many
patients prefer to intermittent injections. Systemic PCA usually connotes intravenous drug
administration, but it also can be subcutaneous or intramuscular. Few studies of the use of
PCA drug delivery to the epidural space exist. A typical intravenous PCA prescription
applicable to many contexts relies on a series of "loading" doses: for example, 3-5 mg of
morphine, repeated every 5 minutes until the initial postoperative pain (if present) diminishes.
A low-dose basal infusion (0.5-1 mg/hr) at night allows uninterrupted sleep. On-demand
doses typically add l mg of morphine every 6 minutes, with a total hourly limit of 10 mg. Once
the patient is able to take oral medications, an around-the-clock schedule of an oral opioid
such as a codeine-acetaminophen combination is provided, and the basal infusion rate is
discontinued. By observing the number of "on-demand" doses self-administered by the
patient, the clinician can assess the adequacy of the oral medication and titrate it further,
change to a stronger compound such as oxycodone with acetaminophen, or discontinue the
PCA pump.

Intravenous administration is the preferred route for postoperative opioid therapy when the
patient cannot take oral medications. When intravenous access is problematic, sublingual
and rectal routes should be considered as alternatives to traditional intramuscular or
subcutaneous injections. All routes other than intravenous require a lag time for absorption of
the drug into the circulation. In addition, repeated injections with associated pain and trauma
may deter some patients, especially children, from requesting pain medication. Continuous
administration of low doses of opioids intravenously or transdermally and intermittent delivery
across the buccal mucosa are relatively new but apparently effective methods to administer
opioids postoperatively. Further experience is needed to define the clinical roles of these
innovative methods in relation to more well-established methods.

Opioids and local anesthetic agents interact favorably. Continuous administration into the
epidural space of low concentrations of opioids in dilute solutions of local anesthetic provides
excellent analgesia, while reducing the potential risks (e.g., respiratory depression or motor
block) associated with equianalgesic concentrations of either agent administered singly. In a
less technologically demanding approach, systemically administered opioids given pre-,
intra-, or postoperatively augment the duration and effectiveness of local anesthetics given
spinally or epidurally. Local anesthetics alone may be applied intermittently to specific nerves
to interrupt pain pathways. For example, injecting local anesthetics around the intercostal
nerves after thoracotomy significantly improves pulmonary function. Catheters for continuous
or repeated intermittent dosing of local anesthetic also have been employed postoperatively
in the pleural space or adjacent to nerves such as the brachial plexus or cervical sympathetic
ganglia. However, a clinical role for interpleural or perineural local anesthetics in the
postoperative setting has not yet been defined.

Nonpharmacologic Management

Nonpharmacologic interventions can be classified as either cognitive-behavioral interventions

or physical agents. Cognitive and behaviorally based approaches include several ways to
help patients understand more about their pain and take an active part in its assessment and
control. The goals of interventions classified as cognitive-behavioral therapies are to change
patients' perceptions of pain, alter pain behavior, and provide patients with a greater sense of
control over pain. The goals of interventions classified as physical agents or modalities are to
provide comfort, correct physical dysfunction, alter physiological responses and reduce fears
associated with pain-related immobility or activity restriction. Nonpharmacologic approaches
are intended to supplement, not substitute for, the pharmacologic or invasive techniques
described above.

Nonpharmacologic interventions are appropriate for the patient who: 1) finds such
interventions appealing; 2) expresses anxiety or fear, as long as the anxiety is not
incapacitating or due to a medical or psychiatric condition that has a more specific treatment;
3) may benefit from avoiding or reducing drug therapy (e.g., history of adverse reactions, fear
of or physiological reason to avoid over sedation); 4) is likely to experience and need to cope
with a prolonged interval of postoperative pain, particularly if punctuated by recurrent
episodes of intense treatment- or procedure-related pain; or 5) has incomplete pain relief
following appropriate pharmacologic interventions. Cognitive-behavioral approaches include
preparatory information, simple relaxation, imagery, hypnosis, and biofeedback. Physical
therapeutic agents and modalities include application of superficial heat or cold, massage,
exercise, immobility, and electroanalgesia such as TENS therapy.

Giving a patient a detailed description of all medical procedures, expected postoperative

discomfort, and instruction aimed at decreasing treatment- and mobility-related pain can
decrease self-reported pain, analgesic use, and postoperative length of stay. Patients should
receive sufficient procedural and sensory information to satisfy their interest and enable them
to assess, evaluate, and communicate postoperative pain. In addition, all preoperative
patients should receive instruction emphasizing the importance of coughing, deep breathing,
turning, and walking, along with suggestions on how to decrease physical discomforts from
such activities. When fear or anxiety occur, it is important to assess psychological coping
skills and provide practical suggestions for managing pain and maintaining a positive outlook.
Patients who appear anxious or fearful before surgery, and others who express an interest in
cognitive-behavioral strategies, should be assisted in selecting an intervention (e.g., simple
relaxation or imagery) and taught how to use it. In some patients, particularly those with high
levels of anxiety, too much information, or too many demanding decisions can exacerbate
fear and pain. Psychiatric evaluation is appropriate for patients who manifest disabling or
disruptive anxiety symptoms such as emotional instability, restlessness, inability to sleep, and
dulled thinking.

Relaxation is the most widely evaluated cognitive-behavioral approach to postoperative pain

management. Relaxation strategies, including simple relaxation, imagery, hypnosis,
biofeedback, and music-assisted relaxation have all shown some degree of effectiveness in
reducing pain. Relaxation strategies and imagery techniques need not be complex to be
effective. Relatively simple approaches such as the brief jaw relaxation have been successful
in decreasing self-reported pain and analgesic use. These strategies take only a few minutes
to teach but require periodic reinforcement through encouragement and coaching. Supportive
family members or audiotapes often can sustain patient skills. A relaxation strategy that can
be used informally is music distraction. Both patients' personally preferred music and "easy
listening" music have significantly decreased postoperative pain in clinical studies. Patients
who need repeated coaching may benefit from the use of a commercially prepared relaxation
or music-assisted relaxation audiotape.

Other cognitive-behavioral strategies require greater professional involvement; these include

complex imagery, hypnosis, biofeedback, and combined therapies. Such strategies are
commonly applied when patients have chronic pain even before surgery.

Examples of Nonpharmacologic Interventions for Postoperative Pain

Cognitive-Behavioral Physical Agents

education/instruction application of heat or cold

relaxation massage, exercise, and immobilization
imagery transcutaneous electrical nerve stimulation
music distraction
biofeedback

Although some data suggest that the use of complex imagery may reduce pain, that
biofeedback may lessen pain and operative site muscle tension, and that interventions which
combine imagery and relaxation may decrease pain, each requires specialized training and,
for biofeedback, the use of special equipment. Findings from studies of hypnosis for control
of postoperative pain are inconsistent. Insufficient research to demonstrate effectiveness in
reducing postoperative pain and the need for special training or equipment preclude the
recommendation of complex imagery biofeedback, or hypnosis for routine postoperative pain
control. This is not to say that patients who have a high level of preoperative anxiety, whose
pain is severe and enduring, or who suffer recurrent episodes of procedure-related pain will
not benefit from these strategies. However, for such patients a more comprehensive pain
management program must include active involvement of professionals skilled in cognitive-
behavioral therapy and psychological assessment.

In addition to cognitive-behavioral interventions, several physical therapeutic methods can be

used to manage pain. Commonly used physical agents include applications of heat and cold
massage, exercise, and rest or immobilization. Applications of heat or cold are used to alter
pain threshold, reduce muscle spasm, and decrease congestion in an injured area.
Applications of cold are used initially to decrease tissue injury response. Later, heat is used
to facilitate clearance of tissue toxins and accumulated fluids. Massage and exercise are
used to stretch and regain muscle and tendon length. Immobilization is used following many
musculoskeletal procedures to provide rest and maintain the alignment necessary for proper
healing. With the exception of applications of cold and immobilization, these interventions
typically are not used following surgery unless complications occur or an extended
postoperative course is expected. When physical modalities are used, it is often for a
physiological goal other than pain relief. Of these modalities only cryotherapy (application of
cold) has been evaluated in the literature. There is insufficient evidence to suggest that
cryotherapy alone is effective in reducing postoperative pain. Cryotherapy is different from
cryoanalgesia (application of a cryoprobe to specific peripheral nerves), which has proven
effective for post-thoracotomy pain

TENS therapy is one physical modality for which there is some support. TENS therapy has
been effective in reducing self-reported pain and analgesic use following abdominal surgery,
orthopedic surgery, thoracic surgery, mixed surgical procedures, and cesarean section.
TENS therapy also has improved physical mobility following thoracic and orthopedic surgery.
Both TENS therapy and sham TENS therapy (that is, application of electrodes without
transmission of electric current) significantly reduced analgesic use and subjective reports of
pain. No significant differences were found between TENS therapy and sham-TENS. Even
though these findings suggest a placebo effect underlies the reduction of perceived pain and
analgesic use during TENS therapy, beneficial effects do, in fact, result. The physical
modalities of acupuncture and electroacupuncture also have been clinically evaluated in
postoperative patients, with conflicting findings; no clear analgesic effect has been
demonstrated.

How each patient's postoperative pain management program is designed and implemented
will vary according to the type of medical facility and services available to support a pain
management program. At the least, clinicians should be introduced to these methods so they
recognize the benefits of cognitive-behavioral and physical interventions, know the
indications for their use, and are able to provide information and counseling to patients. In
addition, patients should have access to written information about available therapies, why
and when to use them, and sources for self-management materials or professional
consultations.

Catastrophic postoperative events are rarely, if ever, masked by any of the approaches to
postoperative pain control previously described. Any sudden or unexplained change in pain
intensity requires immediate evaluation by the surgeon. Likewise, a sudden increase in
anxiety may signal cardiac or pulmonary decompensation and requires prompt medical or
surgical assessment.

Dental Surgery

The most common forms of dental surgery are brief and relatively noninvasive procedures
often performed on an outpatient basis. A patient's anxiety is frequently disproportionate to
the safety of the procedure; such a patient may benefit from behavioral or pharmacologic
(anxiolytic) therapy. Mild pain associated with most forms of uncomplicated dental care such
as simple tooth extractions, endodontic therapy, or scaling of the periodontal area or of a
previously asymptomatic tooth is well managed by oral administration of an NSAID such as
aspirin or ibuprofen. Preoperative administration of ibuprofen appears to delay the onset of
postoperative pain and lessen its severity. For patients unable to tolerate aspirin or ibuprofen,
acetaminophen can provide an acceptable analgesic effect.

Dental procedures such as surgical removal of bony impactions and osseous periodontal
surgery are more traumatic and typically produce intense and prolonged postoperative pain.
The onset of such pain can be delayed by preoperative treatment with ibuprofen and/or
application of a long-acting local anesthetic such as bupivacaine during the procedure.

Rarely, an intravascular or intraneural injection of local anesthetic in this context leads to

bruising, bleeding, or systemic symptoms such as fainting, allergic reaction, or persistent pain
due to direct nerve injury. When postoperative pain

does emerge, it often requires the addition of an opioid to the nonsteroidal regimen. Codeine
is frequently prescribed at a dosage of 30-60 mg every 4-6 hours. Increased analgesia–but
also an increased number of opioid side effects such as nausea, constipation, sedation, and
respiratory depression–follow dosage increases above this level. Alternative opioids include
propoxyphene or oxycodone administered in doses that are equainalgesic to 30-60 mg of
codeine.

Some operations on the oral cavity preclude the patient's taking oral medications
postoperatively (e.g., wiring the mouth closed after an operation on a mandibular fracture).
Alternative therapy should be based on the severity of the surgical procedure and expected
pain associated with it, as well as the surroundings in which it will be managed. Formulations
of NSAIDs such as rectal suppositories (indomethacin) or intramuscular injection (ketorolac)
are now commonly available. Opioids may be administered by a variety of routes
(intravenous, intramuscular, subcutaneous injection, transdermal, rectal) and schedules,
including a patient controlled schedule. Cost-efficacy analyses of parenteral opioid
administration for oral surgery are not sufficient to permit any clear recommendations. Pain
that does not respond to these measures should prompt a search for infection, osteitis,
peripheral nerve injury, or the emergence of psychological and behavioral changes
consistent with the development of chronic pain syndrome.

Analgesics for Pain Management

ANALGESICS

Pain Control

Pain, as defined by the International Association for the Study of Pain, is "an unpleasant
sensory and emotional experience arising from actual or potential tissue damage or
described in terms of such damage." It is often pain that brings the patient to the dental office.
Conversely, fear of pain is a significant reason for many people to avoid seeking dental care.
No matter how successful or how deftly conducted, most dental procedures produce tissue
trauma and release potent mediators of inflammation and pain. We now know that unrelieved
pain after surgery or trauma has negative physical and psychologic consequences.

The two components of pain are perception and reaction. Perception is the physical
component of pain and involves the message of pain that is carried through the nerves
eventually to the cortex. Reaction is the psychological component of pain and involves the
patient's emotional response to the pain. Although individuals are surprisingly uniform in their
perception of pain, they vary greatly in their reaction to it. A decrease in the pain threshold (a
greater reaction to pain) has been associated with emotional instability, anxiety, fatigue,
youth, certain nationalities, women, and fear and apprehension. The pain threshold is raised
by sleep, sympathy, activities, and analgesics.

Fortunately, pain is preventable or controllable in an overwhelming majority of cases.

Patients have a right to treatment that includes prevention of pain and adequate relief of pain.

Undertreatment of pain is a significant problem. Numerous clinical surveys have shown that
postoperative pain is often inadequately treated because of undermedication, leaving
patients to suffer needlessly.

Successful assessment and control of pain depend, in part, on establishing effective

communication between the dentist and the patient. Patients should be informed that pain
relief is an important part of their health care. Pain is a subjective phenomenon. The patient's
self-report is the single most accurate and reliable indicator of the existence and intensity of
pain and any resultant distress. Pain is whatever the experiencing person says it is and exists
whenever he says it does.

A significant barrier to the effective use of analgesics in managing pain involves several
misconceptions regarding pain and its control held by both patients and health care
providers.
Misconception 1- Patients who are in pain always have observable signs. Although many
patients in acute pain exhibit evidence of anxiety, distress, or decreased function, many do
not.

Misconception 2- Obvious pathology, test results, and/or the type of surgery determine the
existence and the intensity of pain. Although the ability to identify a pathologic process
underlying a patient's pain complaint is a key element in planning and initiating definitive
treatment, failure to identify the source of a patient's pain does not necessarily mean than it
does not exist.

Misconception 3- Patients should wait as long as possible before taking a pain medication.
This abstinence will teach them to have a better tolerance for pain. Pain that is untreated
often escalates. Without treatment, sensory input from injured tissue reaches spinal cord
neutrons and causes subsequent responses to be enhanced. Aggressive pain prevention
and control that occurs before, during, and after a painful event such as dental surgery can
yield both short- and long-term benefits. Patients should be encouraged to use analgesics
before pain becomes severe and difficult to control.

The most common types of odontogenic pain are characterized as acute pain.
Characteristically, acute pain is accompanied by some recognizable evidence of tissue injury
or inflammation, and it resolves spontaneously once the underlying cause (inflamed pulp,
abscessed tooth, carious lesion) is definitively treated. Few underlying psychologic or
behavioral issues affect the dentist's choice of therapies, and, most commonly, a
pharmacologic approach to pain management is most appropriate.

In contrast, management of chronic facial pain involves much more complex treatment
issues. Chronic pain often lasts months or years beyond the precipitating event, and there is
rarely a readily identifiable source, that is, an area of tissue destruction or inflammation.
There is often a complicated set of behavioral issues that must be explored and clarified.
Pharmacologic approaches to chronic pain are rarely the sole or principal means of
managing these disorders.

Peripherally acting analgesics reduce or control pain by directly inhibiting the biochemical
mediators of pain at the site of injury. In addition to their analgesic property, the majority of
drugs in this class have antiinflammatory and antipyretic activity. In fact, they are often
referred to as the NSAIDs or antipyretic analgesics.

Opioids on the other hand, decrease the perception of pain in the CNS. The opioid
analgesics act in the CNS at receptors in the spinal cord, rostroventral medulla, and
periaqueductal gray matter. These anatomic loci are considered important to the perception
of pain.

Analgesic Agents

Analgesic agents can be divided into two groups: the nonopioid, nonnarcotic and the opioid
narcotic. An important difference between the nonopioid and the opioid analgesics is their
site of action. Nonopioid analgesics act primarily at the peripheral nerve endings, although
they also act centrally. Opioids act within the central nervous system.
Another difference between the opioids and the nonopioid analgesic agents is their
mechanism of action. The action of the nonopioid analgesic agents is related to their ability to
inhibit prostaglandin synthesis. The opioids affect the amount of pain by depressing the CNS
(the reaction).

Nonsteroidal antiinflammatory drugs (NSAIDs) act at the site of initiation of noxious impulses.
Although it is difficult to separate their antiinflammatory effects from their analgesic effects,
nonopioid drugs such as the salicylates and other NSAIDs work predominantly in the
periphery by preventing the synthesis and release of inflammatory mediators that sensitize
noninceptive receptors to other algesic mediators, such as bradykinin, and to physical forces.
Recent studies suggest that NSAIDs may also have central effects. Acetaminophen has been
shown to have analgesic and antipyretic properties, but it lacks significant antiinflammatory
effects. Acetaminophen appears to exert its effects both in the CNS and in the periphery.

The peripherally acting or antipyretic analgesics comprise various chemical classes of drugs
that have a similar mechanism of action and share clinically important analgesic,
antiinflammatory, and antipyretic properties. These analgesics are widely prescribed by
dentists and physicians because they can be taken orally, they do not cause central nervous
system (CNS) or respiratory depression at therapeutic doses (as do the centrally acting
opioid analgesics), and, most important, they are very effective pain relievers.

Aspirin and acetaminophen have been recognized for many years as prototypes for the
peripherally acting analgesics. Today, the propionic acid derivatives, led by ibuprofen, have
successfully challenged the clinical status of these older drugs and have established a new
standard for comparison. Some of the claims made for these agents are greater peak
analgesia, longer durations of action, and a lower incidence of side effects. Because the
dentist must treat acute pain on a daily basis, the peripherally acting analgesics are of
particular importance.

Nonopioid Analgesics

This category comprises various groups of drugs that have a similar mechanism of action
and share clinically important analgesic, antiinflammatory, and antipyretic properties. These
agents differ from opioid analgesics in the following ways: (1) there is a ceiling effect to the
analgesia; (2) they do not product tolerance or physical dependence; (3) they are antipyretic;
and (4) they possess both antiinflammatory as well as analgesic properties, except for
acetaminophen, which has minimal antiinflammatory activity. Pharmacologic management of
mild to moderate pain should begin, unless there is a contraindication, with a nonopioid drug
such as acetaminophen, a salicylate, or another NSAID. As a general rule, any analgesic
regimen should include a nonopioid drug, even if pain is severe enough to require the
addition of an opioid.

Nonopioids are most effective in treating postprocedural pain when given before the
procedure ( or immediately following a short procedure), thus preventing the synthesis of
prostaglandins that quickly follow the surgical insult. The delayed use of NSAIDs post-
procedurally inhibits the subsequent prostaglandin synthesis and provides analgesia, but it
does not interfere with the effects of those prostaglandins already produced. Preoperative
administration of NSAIDs delays the onset of postoperative pain and lessens its severity and
subsequent analgesics requirements.
The NSAIDs all share a qualitatively similar side-effect profile. However, with the exception of
a true allergic reaction and the bronchoconstriction response in asthmatics, a patient's
inability to tolerate one specific NSAID does not mean the patient will be intolerant of all other
NSAIDs. Also, patients may vary in their relative analgesics response to various NSAIDs.
Therefore, if a patient does not respond to a particular drug at the maximum therapeutic
dose, an alternative NSAID should be considered.

The oral route of administration is preferred for nonopioids. Some patients, such as young
children or patients with intermaxillary fixation following maxillofacial surgery or trauma, are
unable to swallow tablets or capsules. For these patients, liquid formulations of
acetaminophen or ibuprofen should be considered. For the rare dental patient who is unable
to take any medications by mouth, parenteral (ketorolac) or rectal (acetaminophen, aspirin)
dosage forms are available.

The nonopioids can be divided into the salicylates (aspirin-like group), acetaminophen, and
the nonsteroidal anti-inflammatory agents or drugs (NSAIAs/NSAIDs).

Nonopioid Analgesics
Salicylates NSAIAs Acetaminophen

Aspirin Ibuprofen (Tylenol)

Choline salicylate Naproxen
Sodium salicylate Ketoprofen
Salsalate Ketorolac
Magnesium salicylate Diflunsial

The inhibition of prostaglandin synthesis produced by aspirin is also responsible for its
antiinflammatory action, a primary objective in dental pain relief. The prostaglandins are
important vasodilating agents that also increase capillary permeability. Therefore, aspirin
causes decreased erythema and swelling of the inflamed area.

Aspirin and Related Salicylates

Aspirin has been commercially available since 1899, and, until the late 1970s, no peripherally
acting analgesics could claim greater efficacy.

Aspirin belongs to the salicylic acid (salicylate) class of compounds that were originally
obtained from botanical sources. The first active substance of this group, salicin, was isolated
from the bark of the willow tree. From salicin were synthesized salicylic acid, sodium
salicylate, and finally acetylsalicylic acid (aspirin).

Aspirin, the most prominent member of the salicylate group, derives its analgesic, antipyretic,
and antiinflammatory action from its ability to inhibit prostaglandin systhesis. Aspirin inhibits
the enzyme cyclooxygenase (prostaglandin synthase) by acetylating a serine, which results
in inhibition of the production of prostaglandins. A reduction in prostaglandins results in a
reduction in painful perception. Many dental patients are advised to take aspirin before the
painful stimuli is experienced, such as a "throbbing" pain caused by inflammation.

The antipyretic properties of aspirin are well documented. Antipyresis is best demonstrated in
febrile patients, since normal subjects show no marked change in body temperature when
therapeutic doses of aspirin are administered.

It is difficult to separate the analgesic and antiinflammatory effects of aspirin, since the vast
majority of painful conditions have an inflammatory component. There is little doubt that the
cascade of reactions leading to the formation of prostaglandins is integrally involved with the
inflammatory response and that aspirin's efficacy in treating inflammation is closely related to
its inhibition of prostaglandin synthesis.

Aspirin is rapidly and almost completely absorbed from the stomach and small intestine,
producing a peak effect on an empty stomach in 30 minutes. The buffered tablet reaches its
peak in about 50 minutes. Addition of a buffer to aspirin facilitates the dispersion and
dissolution of the tablet.

Aspirin may be administered rectally when vomiting is present. Since this route is more
erratic and unpredictable it should only be used when the oral route is not feasible. An aspirin
tablet should never be applied topically to the oral mucosa to treat a toothache. A painful
ulceration can occur.

Aspirin is typically used to relieve mild to moderate pain such as a headache or toothache. It
is not effective against intense pain because the analgesic potency of aspirin is weaker than
that of the opioids.

Aspirin has been reported to have three kinds of adverse effects on the gastrointestinal
system. The first is gastric distress. There is evidence suggesting that both local and
systemic mechanisms interfere with the ability of gastric mucosal cells to resist penetration by
acid. Aspirin's interference with normal cytoprotective mechanisms mediated by
prostaglandins in gastric mucosal cells is a primary cause of the gastric distress. A second
effect of aspirin is occult gastric bleeding, resulting from cellular and capillary damage along
the gastrointestinal tract. The third effect, which is very rare and idiosyncratic, is a sudden
acute hemorrhage.

Aspirin significantly increases bleeding time by inhibiting the aggregation of platelets. As little
as one 325 mg aspirin tablet can double the normal bleeding time for several days. This
protracted inhibition of platelet aggregation correlates with the ability of aspirin to irreversibly
acetylate cyclooxygenase. Platelets lack the ability to regenerate this enzyme, and the
synthesis of new platelets is required for recovery to occur.

Aspirin in dentistry: Aspirin is an effective analgesic for almost any type of acute dental pain.
Double-blind, controlled studies of the relief of pain after extraction of third molars have
demonstrated that 650 mg of aspirin is substantially more effective than 60 mg of codeine in
relieving postoperative pain. In fact, most controlled clinical studies have established that,
regardless of the cause of the pain, aspirin (650 mg) provides equal or greater pain relief
than codeine (60 mg). A problem with aspirin is that it has a rather flat dose-response curve,
with near-maximal analgesia occurring at approximately 650 mg. Increasing the dose to 1000
mg may slightly increase analgesic efficacy and prolong the duration of effect. Clinically, this
means that if 650 to 1000 mg of aspirin fails to relieve the discomfort, increasing the dose will
be of little help. However, it cannot be overemphasized that at this ceiling dosage, taken
every 4 hours, aspirin is a very effective analgesic for most painful dental conditions.

Adverse effects: Aspirin has numerous side effects at therapeutic doses, most of which are
more annoying than serious. The most commonly reported side effect is nausea. It is
important to realize that many surgical procedures or illnesses may cause nausea by
themselves and that the analgesic may be blamed unjustly.

Certainly, many dental surgical procedures have the potential for causing nausea because of
the swallowing of blood and debris, the use of sedative or anesthetic drugs, and the anxiety
associated with dental surgery. However, it is also clear that aspirin can cause gastric
irritation that leads to nausea and, occasionally, vomiting. In addition to the effects of aspirin
on the gastric mucosa, aspirin causes local irritation directly while the tablet is disintegrating
and in contact with the gastric tissues.

The same mechanisms that produce nausea are probably involved in the occult bleeding that
develops in over 70% of those who use the drug. This blood loss occurs each time aspirin is
ingested, occurs even at low doses, and goes unnoticed unless stool tests for blood are
performed. Only in very unusual circumstances is this occult bleeding, which amount to less
than 10 mL/day, of any clinical significance. However, aspirin is contraindicated in patients
with gastrointestinal ulcers, especially those with peptic ulcers, because the normally
innocuous bleeding may lead to severe internal hemorrhaging.

Aspirin significantly increases bleeding time by inhibiting the aggregation of platelets.

Although the prolongation of clotting time is tolerated in healthy patients, the possibility exists
that aspirin could promote postoperative hemorrhaging, especially if a clot has not fully
formed. In two studies of patients undergoing dental impaction surgery, the administration of
analgesic doses of aspirin was associated with significantly more postoperative swelling than
comparable doses of acetaminophen. In view of these experimental findings, it may be
prudent to recommend that aspirin therapy be discontinued before surgical procedures such
as tooth extraction and that aspirin not be used prophylactically before any procedure that
may involve postoperative bleeding. However, once a clot has been established, there should
be little problem caused by the administration of aspirin or related salicylates.

Toxicity caused by aspirin overdose is common. Its symptoms and severity depend on dose.
Chronic toxicity caused by salicylates is called salicylism and is characterized by tinnitus,
nausea, vomiting, headache, hyperventilation, and mental confusion. Aspirin holds the
dubious distinction of being one of the more frequently used drugs for attempted suicides.

The hyperventilation eventually can lead to respiratory alkalosis, which may be followed by a
combined respiratory and metabolic acidosis accompanied by dehydration. Acidosis is more
prominent as the level of overdose increases. Acidosis is also more likely to occur in children
and infants. Impaired vision, hallucinations, delirium, and other CNS effects may be evident,
and the situation is considered life threatening.

The treatment of aspirin overdose is primarily palliative and supportive. Chronic toxicity
usually only requires removal of the drug and eventual dose adjustment. Acute toxicity often
requires respiratory support, gastric lavage, maintenance of electrolyte balance (e.g.,
potassium replacement if necessary), maintenance of plasma pH, and alkalinization of the
urine by intravenous (IV) bicarbonate.

Intolerance to salicylates can occur, with symptoms ranging from rhinitis to severe asthma.
The reaction is more common in patients with preexisting asthma or nasal polyps. This does
not appear to be an immune-mediated reaction. Intolerance occurs to other NSAIDs as well.
The incidence of this kind of reaction in asthmatic patients has been reported to be as high
as 20%. Patients with a history of asthma, allergic disorders, or nasal polyps should be
questioned to be sure that they can tolerate aspirin.

Aspirin is contraindicated in a number of medical conditions. Serious internal bleeding can

result from the ingestion of aspirin by a patient with an ulcer condition.

Aspirin is not contraindicated in pregnancy, but it should be used with caution. In the third
trimester, aspirin tends to prolong labor by inhibiting the synthesis of prostaglandins involved
in initiating uterine contractions. Aspirin has also been reported to increase blood loss at the
time of delivery and may cause premature closure of the ductus arteriosus in the fetus.
Aspirin should also be avoided in children with influenza or chickenpox (varicella). There are
epidemiologic data indicating that aspirin usage during or shortly after these viral diseases
increases the risk of developing Reye's syndrome.

Contraindications to the Use of Aspirin and Other Salicylates

Disease state Possible adverse effect of aspirin

Ulcer Internal bleeding, possible hemorrhaging

Asthmatic attack resembling an allergic
Asthma
reaction
High doses may cause hyperglycemia or
Diabetes
hypoglycemia
Low doses increase plasma urate; high doses
Gout
lower plasma urate
Influenza Reye's syndrome in children
Hypocoagulation states Excessive bleeding

It is obvious that aspirin is not an innocuous drug. However, there are relatively few
instances in which clinically significant side effects occur, and, if reasonable precautions are
taken to avoid aspirin when its use is contraindicated, the drug is an extremely effective and
safe analgesic.

Acetaminophen

Acetaminophen is the only aniline derivative currently in clinical use. It is widely promoted as
the antipyretic analgesic of choice when aspirin cannot be used because of gastric problems
or other contraindications.
Acetaminophen has both analgesic and antipyretic activity that is essentially equivalent to
that of aspirin. Acetaminophen's mechanism of action also appears to be the same as that of
aspirin.

Compared with aspirin, acetaminophen has relatively few important effects on specific organs
or systems. The potency and efficacy of acetaminophen as an antipyretic are similar to those
of aspirin. At therapeutic doses, acetaminophen has little, if any, effect on the cardiovascular
or respiratory systems. Acetaminophen does not inhibit platelet aggregation, cause occult
bleeding or gastric irritation, affect uric acid excretion, or have as many drug interactions as
aspirin. In overdose, the organ most affected is the liver. Acute renal toxicity may also occur.

The wide publicity given to the adverse effects of aspirin has caused increasing numbers of
dentists to substitute acetaminophen for aspirin in the treatment of postoperative dental pain,
even though the antiinflammatory effects of acetaminophen are minor. In clinical studies,
aspirin and acetaminophen appear to be similar in their effectiveness in relieving pain after
the extraction of third molars.

Until recently, acetaminophen was thought to have a plateau for analgesia at about 650 mg,
but it is now accepted that acetaminophen does have a linear dose-effect curve for analgesia
up to 1000 mg. Based on this finding, some clinicians are recommending the use of 1000 mg
of acetaminophen rather than the customary 650 mg dose.

The potential for adverse effects from acetaminophen seems to be singularly confined to the
situation in which there is an acute overdose. At therapeutic doses, acetaminophen does not
cause nausea, inhibit platelet aggregation, prolong prothrombin time, or produce the other
side effects associated with the use of aspirin. Allergy to acetaminophen is rare and is
generally manifested as skin eruptions.

Analgesic Alternatives to Aspirin and Acetaminophen

Until the late 1970s, no single-entity oral analgesic had consistently demonstrated grater
analgesic efficacy than that of aspirin or acetaminophen. Several new peripherally acting
analgesics, most of which had earlier been approved for use as antiinflammatory drugs, have
now been evaluated in postoperative dental pain and found to be superior to the standard
drugs in peak analgesic effect, duration of effect, or both.

Among the NSAIDs, the propionic acid derivatives constitute the largest group of aspirin
alternatives. Ibuprofen, fenoprofen, ketoprofen, and naproxen are approved for use as
analgesics. Others, such as flurbiprofen, are currently under review by the Food and Drug
Administration (FDA).

Ibuprofen was the first single-entity oral analgesic to be approved by the FDA that showed a
greater peak effect than 650 mg. of aspirin. It is also available as a nonprescription drug. The
recommended prescription analgesic dose of ibuprofen is 400 mg every 5 to 6 hours. In one
study, this dose was more effective than a combination of 650 mg aspirin with 60 mg
codeine.

Naproxen is approved for a variety of inflammatory conditions and for the relief of pain. It is
available as both the free acid and as the sodium salt, the latter of which is more rapidly
absorbed from the gastrointestinal tract and may be preferred form for analgesic use. The
recommended analgesic regimen for naproxen is 500 mg initially, followed by 250 mg every 6
to 8 hours. Its longer half-life allows dosing at longer intervals than with ibuprofen.

Fenoprofen is marketed with both analgesic and antiinflammatory indications. The

recommended dose of 200 mg every 4 to 6 hours is likely to be superior to 650 mg of aspirin.

Adverse effects: The adverse effects of the peripherally acting analgesics are similar to those
produced by aspirin; however, they may vary in severity. Gastric irritation (nausea and
abdominal pain) is usually the most troublesome adverse effect. Dizziness, gastrointestinal
bleeding, fluid retention, and nephrotoxicity have also been reported. Inhibition of platelet
aggregation is transient and reversible.

These peripherally acting analgesics should be avoided in most patients whose medical
conditions contraindicate the use of aspirin. Of particular concern are patients with
gastrointestinal ulcers, coagulation disorders, and aspirin intolerance.

Opioid Analgesics

Opioid analgesics are primarily employed for the relief of pain and consequently find
widespread application in dentistry. Opioids also possess therapeutically useful antitussive
(cough suppressant) and constipating effects in addition to several undesirable effects,
including respiratory depression, urinary retention, sedation, nausea and vomiting, and at
times unwanted constipation. Repeated use of opioids for control of pain can lead to
analgesic tolerance (loss of analgesic effect), as well as physical and sometimes psychologic
dependence. These shortcomings notwithstanding, no other drugs are more efficacious as
analgesics than the opioids.

Opioid analgesics are added to nonopioids to manage pain that is moderate to severe or that
does not respond to nonopioids alone. Opioids differ from the nonopioids in that they have no
ceiling effect. The only dosing limitation is based on side effects. Although opioids are the
cornerstone for management of moderate to severe acute pain, they are frequently
underutilized and at lower than effective doses as a result of misconceptions and fears
regarding their use.

Fear of possible sedation or respiratory depression causes some practitioners to

underprescribe and underdose opioids. These adverse events rarely occur when appropriate
starting doses are used and then titrated to an effect based on the patient's analgesic
response and side effects. Patients vary greatly in their analgesic dose requirements and
responses to opioid analgesics.

Fear of addiction on the part of both the practitioner and the patient is a common barrier to
the effective use of opioid analgesics. For many, this fear is the result of not being aware of
the actual risks associated with opioid analgesics used for the treatment of pain and of
confusing addiction with physical dependence, tolerance, or pseudoaddiction. Addiction
refers to psychologic dependence, a behavioral pattern of drug use marked by craving, drug-
seeking behavior, and compulsive use that may interfere with the person's ability to function
in society. Physical dependence, on the other hand, is a pharmacologic property causing the
appearance of withdrawal symptoms when the medication is stopped abruptly or following
the administration of an antagonist, and tolerance is the requirement for increased doses of a
drug to achieve the same effect. Finally, pseudoaddiction is a term used to describe
exaggerated behaviors seen in pain patients brought on by inadequate pain relief.

Physical dependence and tolerance are involuntary mechanisms that occur in virtually all
patients taking opioid analgesics for a prolonged period of time. They are easily managed in
the patient with pain. Tolerance is managed with careful upward titration of the dose until
adequate pain relief is reobtained. The effects of physical dependence are easily avoided by
the gradual tapering of opioids on discontinuation of therapy, as opposed to abrupt
withdrawal. Addiction, by contrast, is a voluntary mechanism that rarely occurs in patients
taking opioid analgesics for pain. The overwhelming majority of patients taking pain
medication stop taking the medication when the pain stops.

Opioid analgesics include both pure agonists, such as codeine and oxycodone, and
agonist/antagonists, such as pentazocine and butorphanol. As a general rule, the
agonist/antagonists should not be used as first-line therapy. There is no convincing evidence
that these drugs offer any advantage over the pure opioid agonists. Agonist/antagonists
become less effective at high doses because of the ceiling effect, frequently cause dysphoria,
and may cause confusion and hallucinations. In addition, they may cause withdrawal
symptoms when given to patients physically dependent on opioid agonists. On occasion, they
may be useful in treating individuals unable to tolerate other opioids.

In 1990, the World Health Organization proposed a stepwise approach for the management
of cancer pain. This approach has subsequently come to be recommended for the treatment
of noncancer pain as well. The first step, representing mild pain, is to administer a nonopioid
drug. In many dental surgical procedures,

NSAIDs alone can achieve excellent pain control. Pain that does not respond adequately to
nonopioid agents should be treated with the combination of a nonopioid and an opioid such
as codeine, hydrocodone, or oxycodone. Even when insufficient alone to control pain,
NSAIDs can reduce the dose of opioid relief. More severe pain, or pain that persists, should
be treated with a combination of a nonopioid and a stronger opioid, such as morphine or
hydromorphone. At any level, adjuvant agents such as certain anticonvulsants or tricyclic
antidepressants may be added when indicated. Common indications in dentistry include the
treatment of neuropathic pain and some chronic orofacial pain conditions.

The oral administration of opioid analgesics is preferred whenever possible. It is convenient

and inexpensive. Even severe postsurgical pain can be effectively treated with orally
administered opioids in the proper doses. For the patient not able to swallow a pill or capsule,
numerous liquid formulations of opioids are available (codeine, hydrocodone, oxycodone,
and others). Peak drug effects (including side effects) occur 1.5 to 2 hours after the oral
administration of most opioids (sustained-release tablets excepted). Therefore, patients may
take a second opioid dose safely 2 hours after the first dose if the pain persists and side
effects are mild at that time. For patients unable to take medications by mouth, the
intravenous, intramuscular, or rectal routes of administration can be considered. Use of the
intravenous or intramuscular route to deliver analgesics is almost exclusively limited to
inpatient hospital settings. Of the two routes, intravenous administration is preferred.
Intravenous bolus administration provides the most rapid and predictable onset of effect.
Time to peak effect varies with drug lipid solubility, ranging from 1 to 5 minutes for fentanyl to
15 to 30 minutes for morphine.
As mentioned previously, opioids should almost always be administered with nonopioids for
maximum pain relief in dental situations. Many opioids are marketed in combinations with a
nonopioid, and it is the latter component that limits the dose. For example, the upper dose
limit for acetaminophen is 4000 mg/day. Therefore, for combinations containing 325 mg of
acetominophen, the maximum number of tablets/day is 12. For combinations containing 500
mg of acetaminophen, the maximum number of tablets/day is eight. In children under 45 kg,
the limit is 90 mg/kg of acetaminophen.

Morphine

Morphine is the prototypic opioid analgesic and the one about which most is known.
Morphine is widely used for pain control and can be given by virtually any route of
administration.

The CNS effects of morphine are a combination of stimulation and depression and include
analgesia, drowsiness, euphoria-dysphoria, respiratory depression, suppression of the cough
reflex and pupillary constriction.

The analgesia produced by morphine and its congeners occurs without loss of
consciousness. When opioids are administered for relief of pain (or for a cough or diarrhea,
for that matter), it must be appreciated that they provide only symptomatic relief without
alleviation of the cause of the pain (or cough or diarrhea). The analgesia produced by opioid
analgesics is dose dependent and selective in that other sensory modalities (e.g., vision,
audition) are unaffected at therapeutic doses. The standard parenteral analgesic dose of
morphine, 10 mg/70 kg body weight, is considered a therapeutic dose for relief to severe
pain. Greater doses provide greater pain control.

An additional significant feature of opioid analgesics is that they are generally more effective
against continous, dull aching pain than against sharp, intermittent pain. Neuropathic pain,
such as trigeminal neuralgia, is less responsive to opioids than is nociceptive pain. It is also
known that sensitivity to pain and the ability to clear morphine decrease with age, whereas
the elimination half-life of morphine does the opposite; thus, the pain relief provided by
morphine typically increases with age.

Tolerance and dependence. Tolerance is a decreased effect of drug as a consequence of

prior administration of that drug. Accordingly, increasingly greater dose of drug must be
administered over time to produce an effect equivalent to that produced on initial
administration. Tolerance does not develop uniformly to all opioid effects. In general,
tolerance develops to the depressant effects of opioids but not to the stimulant effects. Thus,
tolerance develops to opioid-induced analgesia, euphoria, drowsiness, and respiratory
depression but not, to any appreciable extent, to opioid effects on the gastrointestinal tract or
the pupil.

In the therapeutic setting, the initial indication that tolerance has developed is generally
reflected in a shortened duration or reduced analgesic effect. The rate at which tolerance
develops is function of the dose and the frequency of administration, as well as perhaps
other, nonpharmacologic factors. In general, the greater the opioid dose and the shorter the
interval between doses, the more rapid is the development of tolerance. Tolerance, in fact,
can develop to such an extent that the lethal dose of the opioid is increased significantly.
However, for any individual there always exists an opioid dose capable of producing death by
respiratory depression regardless of the extent to which tolerance has developed.

Tolerance becomes apparent during repeated drug administration, whereas dependence is

apparent only in the absence of drug. Dependence can be physical or psychologic state
produced by repeated administration of a drug, which then makes its continued use
necessary to prevent the appearance of a withdrawal or abstinence syndrome. The greater
the opioid dose and the longer the duration of administration, the greater is the degree of
physical dependence and the more intense is the withdrawal syndrome.

Psychologic dependence is more difficult to define and measure. Psychologic dependence

contributes more to drug-seeking behavior than does physical dependence. Addiction is the
extreme of compulsive drug use and is associated with significant psychologic dependence,
and thus, it is inappropriate to identify as "addicted" a person who becomes physically
dependent after repeated opioid administration during hospitalization. All three phenomena-
tolerance, physical dependence, and psychologic dependence- are reversible, although
psychologic dependence provides a strong drive to drug abuse.

There exists on the part of health professionals and patients alike concern about the use of
opioids for pain control, particularly in cases of persistent pain. This so-called "opiophobia" is
a reaction to fear of dose escalation (caused by development of tolerance) and subsequent
physical dependence (erroneously termed "addiction") associated with treatment for pain that
lasts more than a few days. It has been found, for example, that dose escalation for pain
control is usually required only at the start of therapy (i.e., when titrating the dose to provide
adequate analgesia) and that dose requirements tend to stabilize thereafter for long periods
of time.

Pain is the main complaint that initiates a visit to a dentist or physician. Moreover, pain is
almost always present after invasive procedures or surgery. Morphine and other opioid
analgesics are the most efficacious analgesic drugs known and are without peer in their
ability to control pain. As emphasized earlier, these drugs provide only symptomatic relief of
pain without influencing its underlying cause. The opioids, when administered at therapeutic
doses to produce analgesia, also produce a drowsiness from which the patient is generally
easily aroused, as well as "tranquillization." There is without doubt a significant antianxiety or
sedating component in the analgesic effect of opioids. Thus, although nausea and vomiting,
respiratory depression, constipation, and tolerance and physical dependence can be
drawbacks to their use, the opioids undeniably produce an important combination of
desirable effects (e.g., analgesia and sedation) in the suffering patient.

Codeine

As with all opioids analgesics, the analgesic and antitussive actions of codeine (as well as its
respiratory depressant and sedative effects) are central in origin. Codeine is frequently
classified as a "weak" or "mild" opioid analgesic. That codeine is a mild analgesic incapable
of providing an analgesic effect equivalent to morphine is an erroneous, but widely held,
impression. Morphine as an analgesic is about 12 times more potent than codeine when both
drugs are administered intramuscularly. This ratio simply means that approximately 120 mg
of codeine is required to produce an analgesic effect equivalent to 10 mg of morphine. At the
present time, however, doses of codeine in excess of 60 mg (orally) are not commonly used
and, moreover, are not officially recognized as generally safe and effective by the Food and
Drug Administration. Consequently, the impression remains that codeine has limited
analgesic efficacy and that a dose of 60 mg of codeine represents an "analgesic ceiling"
above which increasing doses will not provide greater analgesic effect.

It should be noted, however, that dental pain associated with inflammation should not be
treated with codeine alone because neither codeine nor any of the other opioids has
antiinflammatory properties. Rather, aspirin or another nonsteroidal antiinflammatory drug
alone or in combination with codeine is appropriate for cases of dental pain involving or
arising from inflammation.

Principles of Opioid Analgesic Use

Analgesics should be administered initially on a regular time schedule. For example, if the
patient is likely to have pain requiring analgesics for 48 hours after dental surgery, analgesics
might be ordered every 4 hours while awake, not as needed (pro re nata or prn), for the first
36 hours. This schedule provides more stable plasma concentrations of the agent with less
breakthrough pain. If only prn medications are used, it may take several hours and higher
doses to relieve pain, leading to a cycle of undermedication and pain alternating with periods
of overmedication and drug toxicity. Later in the postoperative course, as the patient's
analgesic dose requirement diminishes, dosing may be switched to an as-needed basis.

Adverse Reactions of Opioids

Unlike many drugs, the adverse reactions of the opioids are not related to a direct damaging
effect on hepatic, renal, or hematologic tissues but rather are an extension of their
pharmacologic effects. Like the pharmacologic effects, the adverse reactions of the opioid
analgesics are proportional to their analgesic strength.

1. Respiratory depression. The opioid analgesic agonists depress the respiratory center in a
dose-related manner. This is usually the cause of death with an overdose.

2. Nausea and emesis. Analgesic doses of opioid analgesics often produce nausea and
vomiting. This is due to their direct stimulation of the chemoreceptor trigger zone (CTZ)
located in the medulla. This side effect is reduced by discouraging ambulation.

3. Constipation. The opioids produce constipation by producing a tonic contraction of the

gastrointestinal tract. Small doses of even weak opioids frequently have this effect and its
duration outlasts their analgesic effect. Even with continued administrations tolerance does
not develop to this effect.

4. Urinary retention. The opioids increase the smooth muscle tone in the urinary tract,
thereby causing urinary retention. They also produce an antidiuretic effect by stimulating the
release of antidiuretic hormone (ADH) from the pituitary gland.

5. CNS effects. Occasionally, opioids may produce CNS stimulation exhibited by anxiety,
restlessness, or nervousness.

Combinations of Peripherally Acting Analgesics and Opioids

There is a sound scientific basis for combining peripherally acting analgesics with opioids.
The peripherally acting drugs combat pain principally by directly interfering with the
biochemical mediators that cause sensitization of nerve endings at the site of injury, whereas
the opioids alter CNS perception and reaction to pain. The mechanisms of pain relief of these
two classes of drugs are distinct, supporting the use of these two types of drugs in
combination. In addition to the fact that these combinations seem reasonable, abundant
clinical data exists to support the validity of their combined use. However, there is a common
misconception that such combinations produce a synergistic phenomenon, that is, an effect
greater than the sum of effects expected from both drugs. No evidence currently supports
this belief, and, at best, there is purely additive effect when drugs from these two classes of
analgesics are combined. Indeed, if any synergism does exist, it is probably with the toxic
effects rather than with analgesic efficacy.

The clinical significance of the centrally acting analgesics is that they provide additional
analgesia beyond the ceiling effect of the peripherally acting component, and they also
contribute a centrally mediated sedative effect. Therefore, the most effective combinations
are those that use the optimal amount of an aspirinlike drug combined with the appropriate
dose of an opioid analgesic.

Codeine is the most commonly used centrally acting agent in combination analgesics. Its
effective oral dose range is 30 to 90 mg, 30 mg providing only minimal analgesia, 60 mg
providing a little more analgesia with considerably more nausea and sedation, and 90 mg
approaching the dose at which intolerable side effects appear. Codeine is available in
combination with aspirin or acetaminophen. For most patients, 600 to 650 mg of the
peripherally acting component combined with either 30 or 60 mg of codeine should provide
adequate pain relief for almost any acute dental pain.

There are other centrally acting analgesics used in combination, but the vast majority of drug
combinations on the market include codeine, oxycodone, hydrocodone, propoxyphene, or
pentazocine combined with either aspirin or acetaminophen.

The advent of the NSAIAs has produced a dramatic decrease in the use of the opioids in
dental practice. Most dental pain can be better managed by the use of NSAIAs. In the patient
in whom NSAIAs are contraindicated, the dentist has a wide range of opioids from which to
choose. By beginning with codeine or hydrocodone combinations and progressing to
oxycodone combination, almost all dental pain can be managed. Only in rare cases, and for
very short periods of time (1 to 2 days), should hydromorphone or meperidine be prescribed
for outpatient dental pain.

Dentists should be familiar with several analgesics in both the opioid and nonopioid
categories. Different patients vary greatly in their response to, and ability to tolerate, different
agents. For this reason, it is important to be familiar with the recommended dose, side-effect
profile, and time course of several agents in each category.

Patient should be followed closely, particularly when beginning or changing analgesic

regimens. Analgesics are more beneficial if the clinician monitors pain relief and adverse
effects frequently and adjusts the regimen as needed to optimize therapy. This monitoring is
particularly important when using an agent or combi- nation with which the doctor has little or
no experience or when changing from one analgesic to another.
Although pain is a common occurrence in patients seeking or undergoing dental care, it is
generally manageable and often avoidable. Accurate assessment, methodical prevention,
and aggressive treatment are the tools required to keep pain at a minimum. Rational clinical
practice guidelines and equianalgesic charts allow practitioners to determine the appropriate
analgesic regimen and dose for each patient.