You are on page 1of 14

KEY CONCEPTS

Pain is an unpleasant subjective experience that is the net


effect of a complex interaction of the ascending and descend-
ing nervous systems involving biochemical, physiologic, psy-
chological, and neocortical processes.
Following initial assessment of pain, reassessment should be
done as needed based on medication choice and the clinical
situation.
Effective treatment involves an evaluation of the cause, dura-
tion, and intensity of the pain and selection of an appropriate
treatment modality for the pain situation.
Whenever possible, the least potent oral analgesic should be
selected.
Equianalgesic doses should be used when converting from one
opioid to another.
Pain is dened by the International Association for the Study of
Pain as an unpleasant sensory and emotional experience asso-
ciated with actual or potential tissue damage, or described in
terms of such damage.
1
Pain is an unpleasant subjective expe-
rience that is the net effect of a complex interaction of the ascending
and descending nervous systems involving biochemical, physio-
logic, psychological, and neocortical processes. Pain can affect all
areas of a persons life including sleep, thought, emotion, and
activities of daily living. Since there are no reliable objective
markers for pain, the patients are the only ones to describe the
intensity and quality of their pain.
Pain is the most common symptom prompting patients to
seek medical attention and is reported by more than 80% of
individuals who visit their primary care provider.
1
Despite the
frequency of pain symptoms, individuals often do not obtain
satisfactory relief of pain. This has led to recent initiatives in
health care to make pain the fth vital sign, thus making pain
assessment equally important as obtaining a patients temper-
ature, pulse, blood pressure, and respiratory rate.
EPIDEMIOLOGY AND ETIOLOGY
Prevalence of Pain
Most people experience pain at some time in their lives, and
pain is a symptom of a variety of diseases. For some, pain may
be mild to moderate, intermittent, easily managed, and have
minimal effect on daily activities. For others, pain may be
chronic, severe or disabling, all consuming, and be treatment
resistant. Thus, identifying the exact prevalence of pain is a dif-
cult task. According to the American Pain Foundation, more
than 50 million people in the U.S. suffer from chronic pain,
30 PAIN MANAGEMENT
Christine K. ONeil
LEARNING OBJECTIVES
UPON COMPLETION OF THE CHAPTER, THE READER WILL BE ABLE TO:
1. Identify characteristics of the types of pain: nociceptive, inammatory, neuropathic, and
functional.
2. Explain the mechanisms involved in pain transmission.
3. Select an appropriate method of pain assessment.
4. Recommend an appropriate choice of analgesic, dose, and monitoring plan for a patient
based on type and severity of pain and other patient-specic parameters.
5. Perform calculations involving equianalgesic doses, conversion of one opioid to another,
rescue doses, and conversion to a continuous infusion.
6. Educate patients and caregivers about effective pain management, dealing with chronic
pain, and the use of nonpharmacologic measures.
487
Chisholm_Ch30.qxd 11/6/06 5:59 PM Page 487
488 SECTION 5 / NEUROLOGIC DISORDERS
and an additional 25 million experience acute pain from injury
or surgery.
2
About 20% of adults, mostly women and the eld-
erly, experience chronic pain such as back pain, headache, and
joint pain.
Prevalence rates for a variety of different types of pain have
been described. The annual incidence of moderate-intensity
back pain is 10% to 15% in the adult population with a point
prevalence of 15% to 30%.
3
Migraine affects more than 25 mil-
lion Americans, and 90% of Americans report some other
types of headaches (e.g., tension or sinus) each year.
4
Pain
resulting from bromyalgia affects 4 million Americans.
5
Cancer is commonly associated with both acute and chronic
pain, and about 70% of those diagnosed with cancer will expe-
rience signicant pain.
6
The prevalence of neuropathic pain is unknown because of
the lack of epidemiologic studies. Current estimates suggest
that approximately 1.5% of the population in the U.S. may be
affected by neuropathic pain.
7
However, this gure is probably
an underestimate and will likely increase due to the increase in
disorders associated with neuropathic pain in the ever-growing
older population. Approximately 25% to 50% of all pain clinic
visits are related to neuropathic pain.
8
Central neuropathic pain
is estimated to occur in 2% to 8% of all stroke patients.
9
The elderly, dened as people 65 years of age and over, bear
a signicant burden of pain, and pain continues to be under-
recognized and undertreated in this population. The preva-
lence of pain in people over the age of 60 years is twice that in
those younger than 60 years of age.
10
Studies suggest that 25%
to 50% of community-dwelling elderly suffer pain. Pain is
quite common among nursing home residents. It is estimated
that pain in 45% to 80% of nursing home patients contributes
to functional impairment and a decreased quality of life.
11
The nancial impact of pain is considered to be signicant.
The National Institute for Occupational Safety and Health esti-
mated that the cost of low back pain alone was between $50
billion and $100 billion per year.
12
The American Productivity
Audit of the U.S. workforce, conducted from 2001 to 2002,
revealed that the cost of lost productivity due to arthritis, back
pain, headache, and other musculoskeletal pain was approxi-
mately 80 billion per year.
13
The Undertreatment of Pain
Despite the growing emphasis on pain management, pain
often remains undertreated and continues to be a problem in
hospitals, long-term care facilities, and the community. In one
series of reports, 50% of seriously ill hospitalized patients
reported pain; however, 15% were dissatised with pain con-
trol, and some remained in pain after hospitalization.
14,15
Misconceptions about pain management, both from
patients and health care providers, are among the most com-
mon causes of analgesic failure. Some clinicians may be hesi-
tant to treat pain because they do not believe the patients
reports of pain or feel the patient is exaggerating symptoms in
order to obtain medications. Inadequate clinical knowledge of
available pain management strategies, including pharmacologic,
nonpharmacologic, and alternative therapy options, also often
leads to suboptimal pain management. In one survey, approxi-
mately three-fourths of physicians cited low competence in pain
assessment as the major barrier to effective pain management.
16
Concerns about opiate misuse, abuse, and diversion also con-
tribute to less than optimal pain management and cause
providers to exercise caution when prescribing opiates for pain.
Misunderstandings about the terms addiction, physical depend-
ence, tolerance, and pseudoaddiction are additional obstacles to
optimal pain management.
Patients may present barriers to pain management by not
reporting pain symptoms because of fear of becoming
addicted or because of cultural beliefs. Elderly patients may
not report pain for a variety of reasons including belief that
pain is something they must live with, fear of consequences
(e.g., hospitalization or loss of independence), or fear that the
pain may be forecasting impending illness, inability to under-
stand terminology used by health care providers, or a belief
that showing pain is unacceptable behavior.
PATHOPHYSIOLOGY
Types of Pain
Several distinct types of pain have been described: nociceptive,
inammatory, neuropathic, and functional.
17
Nociceptive
pain is a transient pain in response to a noxious stimulus at
nociceptors that are located in cutaneous tissue, bone, muscle,
connective tissue, vessels, and viscera. Nociceptors may be clas-
sied as thermal, chemical, or mechanical. The nociceptive sys-
tem extends from the receptors in the periphery to the spinal
cord, brain stem, and to the cerebral cortex where pain sensa-
tion is perceived. This system is a key physiologic function that
prevents further tissue damage due to the bodys autonomic
withdrawal reex. When tissue damage occurs despite the
nociceptive defense system, inammatory pain ensues. The
body now changes focus from protecting against painful stim-
uli to protecting the injured tissue. The inammatory response
contributes to pain hypersensitivity that serves to prevent con-
tact or movement of the injured part until healing is complete,
thus reducing further damage.
Neuropathic pain is dened as spontaneous pain and hyper-
sensitivity to pain associated with damage to or pathologic
changes in the peripheral nervous system as in painful diabetic
peripheral neuropathy (DPN), acquired immunodeciency
syndrome (AIDS), polyneuropathy, post-herpetic neuralgia
(PHN); or pain originating in the central nervous system (CNS),
that which occurs with spinal cord injury, multiple sclerosis, and
stroke. Functional pain, a relatively newer concept, is pain sensi-
tivity due to an abnormal processing or function of the central
nervous system in response to normal stimuli. Several conditions
Chisholm_Ch30.qxd 11/6/06 5:59 PM Page 488
CHAPTER 30 / PAIN MANAGEMENT 489
considered to have this abnormal sensitivity or hyperresponsive-
ness include bromyalgia and irritable bowel syndrome.
Mechanisms of Pain
Pain Transmission
The mechanisms of nociceptive pain are well-dened and pro-
vide a foundation for the understanding of other types of pain.
18
Following nociceptor stimulation, tissue injury causes the
release of substances (bradykinin, serotonin, potassium, hista-
mine, prostaglandins, and substance P) that may further sensi-
tize and/or activate nociceptors. Nociceptor activation produces
action potentials (transduction) that are transmitted along
myelinated A- bers and unmyelinated C bers to the spinal
cord. The A- bers are responsible for rst, fast, sharp pain and
release excitatory amino acids that activate -amino-3-hydroxy-
5-methylisoxazole-4-propionic acid (AMPA) receptors in the
dorsal horn. The C bers produce secondary pain which is
described as dull, aching, burning, and diffuse. These nerve
bers synapse in the dorsal horn of the spinal cord, where sev-
eral neurotransmitters are released including glutamate, sub-
stance P, and calcitonin gene-related peptide. Transmission of
pain signals continues along the spinal cord to the thalamus,
which serves as the pain relay center, and eventually to the corti-
cal regions of the brain where pain is perceived.
Pain Modulation
Modulation of pain (inhibition of nociceptive impulses) can
occur by a number of processes. Based on the gate control the-
ory, pain modulation may occur at the level of the dorsal
horn.
19
Since the brain can process only a limited number of
signals at one time, other sensory stimuli at nociceptors may
alter pain perception. This theory supports the effectiveness of
counterirritants and transcutaneous electrical nerve stimula-
tion (TENS) in pain management. Pain modulation may result
through several other complex processes. The endogenous opi-
ate system consists of endorphins (enkephalins, dynorphins,
and -endorphins) that interact with , , and receptors
throughout the CNS to inhibit pain impulses and alter percep-
tion. The CNS also includes inhibitory descending pathways
from the brain that can attenuate pain transmission in the dor-
sal horn. Neurotransmitters involved in this descending system
include endogenous opioids, serotonin, norepinephrine, -
aminobutyric acid (GABA) and neurotensin. The perception of
pain involves not only nociceptive stimulation but physiologic
and emotional input that contributes to the perception of pain.
Consequently, cognitive behavioral treatments such as distrac-
tion, relaxation, and guided imagery can reduce pain percep-
tion by altering pain processing in the cortex.
Peripheral Sensitization, Central Sensitization, and
Wind-Up
Under normal conditions, a balance generally exists between
excitatory and inhibitory neurotransmission. Changes in this
balance can occur both peripherally and centrally resulting in
exaggerated responses and sensitization such as that observed
in inammatory, neuropathic, or functional chronic pain. Pain
in these settings may occur spontaneously without any stimu-
lus or may be evoked by a stimulus. Evoked pain may arise from
a stimulus that normally does not cause pain (allodynia) such
as a light touch in neuropathic pain. Hyperalgesia, an exagger-
ated and/or prolonged pain response to a stimulus that nor-
mally causes pain, can also occur as a result of increased sensi-
tivity in the CNS.
During normal pain transmission, the AMPA receptors are
activated, but the N-methyl-D-aspartate (NMDA) receptor is
blocked by magnesium.
16
Repeated nerve depolarization causes
release of the magnesium block allowing the inux of calcium
and sodium and results in excessive excitability and amplica-
tion of signals. Continued input from C bers and subsequent
increases in substance P and glutamate causes the activation of
the NMDA receptor, a process referred to as wind-up. Wind-up
increases the number and responsiveness of neurons in the
dorsal horn irrespective of the input from the periphery.
Recruitment of neurons not normally involved in pain trans-
mission or spread occurs leading to allodynia, hyperalgesia, and
spread to uninjured tissues.
20
The wind-up phenomenon sup-
ports the observation that untreated acute pain can lead to
chronic pain and the belief that pain processes are plastic and
not static.
CLINICAL PRESENTATION AND DIAGNOSIS
Classication of Pain
Pain has always been described as a symptom. However, recent
advances in the understanding of neural mechanisms have
demonstrated that unrelieved pain may lead to changes in
the nervous system known as neural plasticity. Since these
changes reect a process that inuences a physiologic
response, pain, particularly chronic pain, may be considered a
disease unto itself.
Pain can be divided into two broad categories: acute and
chronic or persistent pain. Acute pain is also referred to as
adaptive pain since it serves to protect the individual from fur-
ther injury or promote healing.
17
However, chronic pain has
been called maladaptive, a pathologic function of the nervous
system or pain as a disease.
Acute Pain
Acute pain is pain that occurs as a result of injury or surgery
and is usually self-limited, subsiding when the injury heals.
Untreated acute pain can produce physiologic symptoms
including tachypnea, tachycardia, and increased sympathetic
nervous system activity, such as pallor, diaphoresis, and pupil
dilation. Furthermore, poorly treated pain can cause psycho-
logical stress and compromise the immune system due to the
Chisholm_Ch30.qxd 11/6/06 5:59 PM Page 489
490 SECTION 5 / NEUROLOGIC DISORDERS
release of endogenous corticosteroids. This situation accompa-
nied by decreased range of motion and decreased lung capac-
ity can delay recovery from the initial injury. Somatic acute
pain arises from injury to skin, bone, joint, muscle, and con-
nective tissue, and it is generally localized to the site of injury.
Visceral pain involves injury to nerves on internal organs (e.g.,
intestines or liver) and can present as diffuse, poorly differen-
tiated, and often referred pain. Acute pain should be treated
aggressively, even before the diagnosis is established, except in
conditions of head or abdominal injury where pain may assist
in the differential diagnosis.
Chronic Pain
Chronic pain persists beyond the expected normal time for
healing and serves no useful physiologic purpose. Chronic pain
may be nociceptive, inammatory, neuropathic, or functional
in origin; however, all forms share some common characteris-
tics. Chronic pain can be episodic or continuous, or both.
Physiologic responses observed in acute pain are often absent in
chronic pain; however, other symptoms may predominate.
There are four main effects of chronic pain, and these include
effects on physical function, psychological changes, social con-
sequences, and societal consequences. Effects of chronic pain
on physical function include impaired activities of daily living
and sleep disturbances. Psychological components of chronic
pain may include depression, anxiety, anger, and loss of self-
esteem. As a result of physical and psychological changes, social
consequences may ensue such as changes in relationships with
friends and family, intimacy, and isolation. On a societal level,
chronic pain contributes to increased health care costs, disabil-
ity, and lost productivity. Management of chronic pain should
be multimodal and may involve cognitive interventions, physi-
cal manipulations, pharmacologic agents, surgical intervention,
and regional or spinal anesthesia.
Chronic Malignant Pain
Chronic malignant pain is associated with a progressive disease
that is usually life-threatening such as cancer, AIDS, progressive
neurologic diseases, end-stage organ failure, and dementia.
21
The goal is pain alleviation and prevention, often through a sys-
tematic and stepwise approach. Tolerance, dependence, and
addiction are often not a concern due to the terminal nature of
the illness.
Chronic Nonmalignant Pain
Pain not associated with a life-threatening disease and lasting
longer than 6 months beyond the healing period is referred to as
chronic nonmalignant pain. Pain associated with low back pain,
osteoarthritis, previous bone fractures, peripheral vascular dis-
ease, genitourinary infection, rheumatoid arthritis, and coro-
nary heart disease is considered nonmalignant. The numerous
causes of this type of chronic pain make treatment complex and
involves a multidisciplinary approach. Treatment is initially con-
servative but may involve the use of more potent analgesics
including opiates in psychologically healthy patients.
22
Neuropathic Pain
Neuropathic pain may be considered to be a type of chronic
nonmalignant pain involving disease of the central and periph-
eral nervous systems. Neuropathic pain may be broadly catego-
rized as peripheral or central in nature. Examples of neuropathic
pain include PHN, which is pain associated with acute herpetic
neuralgia or an acute shingles outbreak. Peripheral or polyneu-
ropathic pain is associated with the distal polyneuropathies of
diabetes, human immunodeciency virus (HIV), and
chemotherapeutic agents. Types of central pain include central
stroke pain, trigeminal neuralgia, and a complex of syndromes
known as complex regional pain syndrome (CRPS). Complex
regional pain syndrome includes both reex sympathetic dys-
trophy and causalgia, both of which are neuropathic pain asso-
ciated with abnormal functioning of the autonomic nervous
system. One of the newest categories of neuropathic pain is neu-
ropathic low back pain.
The symptoms of neuropathic pain are characterized as tin-
gling, burning, shooting, stabbing, electric shocklike quality,
or radiating pain. The patient may describe either a constant
dull throbbing or burning pain, or an intermittent pain that is
stabbing or shooting. Frequent damage to the peripheral nerves
may be referred to the body region innervated by those nerves.
Traditionally neuropathic pain has been difcult to treat and
involves a variety of therapeutic modalities. Rational choice of
treatment options may be accomplished through evaluation of
the neuropathy and its relationship to peripheral or central nerve
damage. Targeting the mechanistic points in the pain pathway is
another rationale for treating neuropathic pain. For example, cer-
tain opioids, such as methadone, are characterized by NMDA
receptor antagonist activity and are effective in treating pain.
Anticonvulsant drugs are able to block sodium channels in the
peripheral afferent nerve bers. Agents such as tricyclic antide-
pressants, bupropion, and venlafaxine block the release of
monoamines targeting dorsal horn inhibitory mechanisms.
Clinical Presentation of Pain
General
Patients may be in acute distress (acute pain) or
have no signs or symptoms of suffering (chronic pain).
Symptoms
Pain is described based on the following characteristics:
onset, duration, location, quality, severity, and intensity.
Other symptoms may include anxiety depression, fatigue,
anger, fear, and insomnia.
Signs
Acute pain may cause hypertension, tachycardia, diaphore-
sis, mydriasis, and pallor.
Diagnosis
The patient is the only person who can describe the inten-
sity and quality of their pain. There are no laboratory tests
that can diagnose pain.
Chisholm_Ch30.qxd 11/6/06 5:59 PM Page 490
CHAPTER 30 / PAIN MANAGEMENT 491
Rating scales provide a simple way to classify the intensity of
pain, and should be selected based on the patients ability to
communicate (Fig. 301).
27
Numeric scales are widely used and
ask patients to rate their pain on a scale of 0 to 10, with 0 indi-
cating no pain and 10 being the worst pain possible. Using this
type of scale, 1 to 3 is considered mild pain, 4 to 6 is moderate
pain, and 8 to 10 is severe pain. The visual analog scale (VAS) is
similar to the numerical scale in that it requires patients to place
a mark on a 10-cm line where one end is no pain, and the worst
possible pain is on the other end. For patients who have dif-
culty assigning a number to their pain, a categorical scale may
be an option to communicate the intensity of the pain experi-
ence. Examples of this include a simple descriptive list of words
and the Wong-Baker FACES of Pain Rating Scale.
28
Multidimensional assessment tools obtain information
about the pain and impact on quality of life, but are often more
time-consuming to complete. Examples of these types of tools
include the Initial Pain Assessment Tool, Brief Pain Inventory,
McGill Pain Questionnaire, the Neuropathic Pain Scale, and
the Oswestry Disability Index.
2933
Pain Assessment in Challenging Populations
Children Pain interviews may be conducted with children as
young as 3 or 4 years of age; however, communication may be
limited by vocabulary.
34
Terms familiar to children such as
hurt, owie, or boo boo may be used to describe pain. The VAS
is best used with children older than 7 years old. Other scales
based on numbers of objects (e.g., poker chips), increasing
color intensity, or faces of pain may be helpful for children
between 4 and 7 years of age. In children younger than 3 to
4 years, behavioral or physiologic measures, such as pulse or
respiratory rate, may be more appropriate. Pain assessment in
newborns and infants relies on behavioral observation for such
Pain Assessment
Effective pain management begins with a thorough and accu-
rate assessment of the patient. Even though pain is a common
presenting complaint, lack of regular assessment and reassess-
ment of pain remains a problem and contributes to the under-
treatment of pain.
23
Pain Assessment Guidelines and Regulations for Specic
Practice Settings
Screening for pain should be a part of a routine assessment, and
this has led several organizations such as the Veterans Health
Administration and the American Pain Society to declare pain
the fth vital sign. Many states have adopted a bill of rights for
patients in pain. In 2001, the Joint Commission on Accreditation
of Healthcare Organizations (JCAHO) incorporated pain as the
fth vital sign in its accreditation standards.
24
According to the
JCAHO, patients have a right to appropriate assessment and
management of their pain and education regarding their pain.
Following initial assessment of pain, reassessment should be done as
needed based on medication choice and the clinical situation.
Methods of Pain Assessment
A patient-oriented approach to pain is essential, and methods
do not differ greatly from those used in other medical condi-
tions. A comprehensive history (medical, family, and psycho-
logical) and physical exam are necessary to evaluate underlying
disease processes for the source of pain and other factors con-
tributing to the pain.
20
A thorough assessment of the character-
istics of the pain should be completed including questions
about the pain (onset, duration, location, quality, severity, and
intensity), pain relief efforts, and efcacy and side effects of cur-
rent and past treatments for pain. A common mnemonic for
pain assessment is PQRST (Palliative/Provocative, Quality,
Radiation, Severity, and Temporal).
25
Some clinicians have sug-
gested the addition of U (you) to this mnemonic.
26
During the
pain interview, the impact of the pain on the patients func-
tional status, behavior, and psychological states should also be
assessed. Evaluation of psychological status is especially impor-
tant in patients with chronic pain since depression and affective
disorders may be common comorbid conditions. A history of
drug and alcohol use should be elicited due to the potential for
addiction in patients who may require opiates or other pain
medications with a potential for abuse. Other conditions such
as renal or hepatic dysfunction, diabetes, and conditions that
affect bowel function can inuence therapy choices and goals.
A discussion of the patients expectations and goals with respect
to pain management (level of pain relief, functional status, and
quality of life) should also be part of any pain interview.
Pain Assessment Tools
Pain, particularly acute pain, may be accompanied by physio-
logic signs and symptoms, and there are no reliable objective
markers for pain. Many tools have been designed for assessing
the severity of pain including rating scales and multidimen-
sional pain assessment tools.
FIGURE 301. Pain rating scales. (Data from reference 27.)
No
pain
0
No
pain
1 2 3 4 5
Moderate
pain
6 7 8 9 10
Worst
possible
pain
Mid
pain
Moderate
pain
Severe
pain
Simple Descriptive Pain Intensity Scale
1
010 Numeric Pain Intensity Scale
1
No
pain
Pain as bad
as it could
possibly be
Visual Analog Scale (VAS)
2
Very
severe
pain
Worst
possible
pain
1
If used as a graphic rating scale, a 10 cm baseline is recommended.
2
A 10-cm baseline is recommended for VAS scales.
Chisholm_Ch30.qxd 11/6/06 5:59 PM Page 491
492 SECTION 5 / NEUROLOGIC DISORDERS
clues as vocalizations (crying and fussing), facial expressions,
body movements (ailing of limbs and pulling legs in), with-
drawal, and change in eating and sleeping habits.
35
Preschool
children experiencing pain may become clingy, lose motor and
verbal skills, and start to deny pain because treatment may be
linked to discomfort or punishment. School-age children may
exhibit aggressiveness, nightmares, anxiety, and withdrawal
when in pain, while adolescents may respond to pain with
oppositional behavior and depression.
Elderly Most of the previously discussed pain scales can be used
in older persons that are cognitively intact or with mild demen-
tia. The pain thermometer and FACES of pain have been studied
in older persons. In persons with moderate to severe dementia or
those who are nonverbal, observation of pain behaviors, such as
guarding or grimacing, provides an alternative for pain assess-
ment. The Pain Assessment in Advanced Dementia (PAINAD)
tool may be used to quantify signs of pain and involves observing
the older adult for 15 minutes for breathing, negative vocaliza-
tions, facial expression, body language, and consolability.
36
Regardless of which pain assessment tool is used, the practitioner
should rst determine if the patient understands the concept of
the scale to ensure reliability of the instrument.
TREATMENT
General Approach to Treatment
Effective treatment involves an evaluation of the cause,
duration, and intensity of the pain and selection of an appropriate
treatment modality for the pain. Depending on the type of pain,
treatment may involve pharmacologic or nonpharmacologic
therapy or both. General principles for the pharmacologic man-
agement of pain are listed in the section on patient care and
monitoring. Two common approaches to the selection of treat-
ment are based on severity of pain and the mechanism responsi-
ble for the pain (Fig. 302). Clinical practice guidelines for pain
management are available from the American Pain Society, the
Agency for Healthcare Research and Quality, the American
Geriatrics Society, and the American Society of Anesthesiologists.
Selection of Agent Based on Severity of Pain
Whenever possible, the least potent oral analgesic should
be selected.
Guidelines for the selection of therapeutic agents based on
pain intensity are derived from the World Health Organization
(WHO) analgesic ladder for the management of cancer pain
(Table 301).
37
Mild to moderate pain is generally treated with
nonopioid analgesics. Combinations of medium-potency opi-
oids and acetaminophen or nonsteroidal anti-inammatory
drugs (NSAIDs) are often used for moderate pain. Potent opi-
oids are recommended for severe pain. Throughout this pro-
gression adjuvant medications are added as needed to manage
side effects and to augment analgesia. While these guidelines
can be useful for initial therapy, the clinical situation (type of
pain); cost and pharmacokinetic prole of available drugs; and
patient-specic factors (age, concomitant illnesses, previous
response, and other medications) must also be considered.
Pain medications may also be used in the absence of pain in
anticipation of a painful event such as surgery to minimize
peripheral and central sensitization.
Mechanistic Approach to Therapy
Current analgesic therapy is aimed at controlling or blunting
pain symptoms. However, diverse mechanisms contributing to
the various types of pain continue to be further elucidated. An
understanding of these new mechanisms of pain transmission
may lead to improvement in pain management, as pharmaco-
logic management of pain becomes more mechanism- specic.
Use of NSAIDs for inammatory types of pain is an example of
a mechanistic approach. Since several mechanisms of pain often
coexist, a polypharmacy approach seems rational to target each
mechanism.
Two current foci in pain management are to identify the
mechanisms that are responsible for pain hypersensitivity and
to prevent this initial hypersensitivity. Therefore, the goal of
pain therapy is to reduce peripheral sensitization and subse-
quent central stimulation and amplication associated with
wind-up, spread, and central sensitization.
17
Nonpharmacologic Therapy
Nonpharmacologic therapies (psychological interventions
and physical therapy) may be used in both acute and chronic
pain. Psychological interventions can reduce pain as well as
Patient Encounter: Part 1
HPI: BA is a 58-year-old male recently diag-
nosed with lung cancer. Following surgery he
was placed on morphine patient-controlled analgesia (PCA).
He has been using 120 mg of morphine/24 hours with ade-
quate pain control.
PMH: Hypertension x 18 years
FH: Noncontributory
SH: Lives with wife; has four grown children; smoked 2
packs per day x 40 years (quit with diagnosis of lung cancer)
Medications: Hydrochlorothiazide 25 mg every day
Pain assessment: Patient rates pain as 8 on a scale of 1 to 10.
The physician would like to convert him to a combination
preparation of oxycodone and acetaminophen. What
dosing regimen would you suggest?
Six months later, BAs pain is controlled with the escalating
doses of the combination product; however, he has
reached the maximum dose of acetaminophen. What
would you suggest at this time?
Chisholm_Ch30.qxd 11/6/06 5:59 PM Page 492
CHAPTER 30 / PAIN MANAGEMENT 493
the anxiety, depression, fear, and anger associated with pain.
Psychological interventions helpful in management of acute
pain are imagery (picturing oneself in a safe, peaceful place)
and distraction (listening to music or focusing on breathing).
Chronic pain patients may benet from relaxation, biofeed-
back, cognitive-behavioral therapy, psychotherapy, support
groups, and spiritual counseling. Biofeedback teaches patients
to control physiologic responses to pain and has been effective
in headache and chronic low back pain. Cognitive therapy
encourages patients to monitor their perceptions of pain,
reducing stress and negativism. Psychotherapy is very useful
for patients with chronic pain, and it can also assist in treat-
ment of psychiatric comorbidities and help patients to deal
with terminal illnesses.
38
The patient should be educated
about what to expect regarding pain and its treatment
whether pain is acute pain (i.e., preoperative explanations of
FIGURE 302. Pain algorithm. NSAID, nonsteroidal antiinammatory drug; AED, antiepileptic drug; SSRI, selec-
tive serotonin reuptake inhibitor; TCA, tricyclic antidepressant; SNRI, serotonin-norepinephrine reuptake inhibitor;
APAP, acetaminophen.
TABLE 301. Selection of Analgesics Based on Intensity of Pain
Corresponding WHO Therapeutic Examples of Initial
Pain Intensity Numerical Rating Recommendations Therapy Comments
Mild 13/10 Nonopioid analgesic; regular Acetaminophen 1,000 mg Consider adding an
scheduled dosing every 6 hours Ibuprofen adjunct or using
600 mg every 6 hours an alternate
regimen if pain is
not reduced in
12 days.
Moderate 46/10 Add an opioid to the Acetaminophen 325 mg + Consider step up
nonopioid for moderate codeine 60 mg every therapy if pain is
pain; regular scheduled 4 hours Acetaminophen not relieved by
dosing 325 mg + oxycodone 2 or more
5 mg every 4 hours different drugs
Severe 710/10 Switch to a high-potency Morphine 10 mg every
opioid; regular scheduled 4 hours Hydromorphone
dosing 4 mg every 4 hours
WHO, World Health Organization.
Data from reference 37.
Mild/Moderate Severe Visceral Neuropathic Inflammatory Functional
Acute Chronic
Pain
NSAIDS or
APAP
Opioids
Opioids for
Severe
Peripheral
APAP or
NSAIDS
TCA or
Tramadol
Central
Opioids
Add
NSAIDS or APAP
Add Adjuvants
(e.g., AED, TCA)
TCA or AED
Lidocaine
SSRI or SNRI
Long Acting
Opioid
Ong-acting Opioids
(e.g., MS Contin,
Oxycontin)
SSRI/SNRI
Pregabalin
Clonidine or
Baclofen
Chisholm_Ch30.qxd 11/6/06 5:59 PM Page 493
494 SECTION 5 / NEUROLOGIC DISORDERS
expected postsurgical pain) or chronic (patient and family
education in hospice care).
Physical therapy is an essential part of many types of pain sit-
uations. Treatment modalities include heat, cold, water, ultra-
sound therapy, TENS, massage, and therapeutic exercise. Heat
and cold therapy are utilized in a variety of musculoskeletal
conditions (muscle spasms, low back pain, bromyalgia, sprains,
and strains). Heating modalities include local hot packs, paraf-
n wrap, hydrotherapy, and deep-heating methods (ultra-
sound). Cold treatments may be delivered via cold packs, ice
massage, cold water immersion, or coolant sprays. TENS ther-
apy is based on the theory that electrical stimulation of a nerve
in a particular area can block pain impulses originating from
that area. TENS is also believed to release endogenous endor-
phins and enkephalins. Massage therapy is used to relieve mus-
cle tension and stiffness and is also felt to increase endogenous
endorphins. Therapeutic exercise improves not only strength,
endurance, and range of motion, but also provides cardiovascu-
lar, psychological, and other health benets.
Pharmacologic Therapy
Nonopioid Analgesics
Acetaminophen
Acetaminophen, an analgesic and antipyretic, is often selected
as initial therapy for mild to moderate pain and is considered
rst-line in several pain situations such as low back pain and
osteoarthritis.
39
Mechanistically, acetaminophen is believed to
inhibit prostaglandin synthesis in the CNS and block pain
impulses in the periphery. Acetaminophen is well-tolerated at
usual doses and has few clinically signicant drug interactions
except causing increased hypoprothrombinemic response to
warfarin in patients receiving acetaminophen doses of more
than 2,000 mg per day. The maximum recommended dose for
patients with normal renal and hepatic function is 4,000 mg
per day. Hepatotoxicity has been reported with excessive use
and overdose and the risk of this adverse effect increases in
those with hepatitis or chronic alcohol use, as well as those
who binge drink or are in a fasting state. Regular chronic use of
acetaminophen has been associated with chronic renal failure,
but reports are conicting. For these reasons, the maximum
dose should be reduced by 50% to 75% in patients with renal
dysfunction or hepatic disease and in those who engage in
excessive alcohol use.
Aspirin and Other Salicylates
Aspirin, nonacetylated salicylates, and other NSAIDs have anal-
gesic, antipyretic, and anti-inammatory actions. These agents
inhibit cyclooxygenase (COX)-1 and COX-2 enzymes, thereby
preventing prostaglandin synthesis, which results in reduced
nociceptor sensitization and an increased pain threshold.
NSAIDs are the preferred agents for mild to moderate pain in
situations that are mediated by prostaglandins (e.g., rheumatoid
arthritis and osteoarthritis, menstrual cramps, and postsurgical
pain) and in the management of pain from bone metastasis, but
they are of minimal use in neuropathic pain.
Aspirin is effective for mild to moderate pain; however, the
risk of gastrointestinal irritation and bleeding limits frequent
use of this drug for pain management. Direct effects of aspirin
on the gastrointestinal mucosa and irreversible platelet inhi-
bition contribute to this risk which can occur even at low doses.
Hypersensitivity reactions are also possible and may occur in
25% of patients with coexsiting asthma, nasal polyps, or
chronic urticaria. Of additional concern is the potential for
cross-sensitivity of other NSAIDs in this group of patients.
Nonacetylated salicylates (choline magnesium salicylate and
sodium salicylate) have a reduced risk of gastrointestinal effects
and platelet inhibition and may be used in aspirin-sensitive
patients. Diunisal, a salicylic acid derivative, is associated with
fewer gastrointestinal (GI) complaints compared to aspirin, but
platelet inhibition does increase the risk of GI bleeding.
Nonsteroidal Anti-Inammatory Drugs
NSAIDs provide analgesia equal to or better than that of aspirin
or acetaminophen combined with codeine, and they are very
effective for inammatory pain and pain associated with bone
metastasis.
18
These agents may be classied by their chemical
structures (fenamates, acetic acids, propionic acids, pyranocar-
boxylic acids, pyrrolizine carboxylic acids, and COX-2 inhibitors).
While only some members of this class have approval for treat-
ment of pain, it is likely that all of them have similar analgesic
effects. All members of this class appear to be equally effective,
but there is great intrapatient variability in response. After an
adequate trial of 2 to 3 weeks with a particular agent, it is rea-
sonable to switch to another member of the class. NSAIDs
demonstrate a at dose-response curve, with higher doses pro-
ducing no greater efcacy than moderate doses, but resulting in
an increased incidence of adverse effects (gastrointestinal irrita-
tion, hepatic dysfunction, renal insufciency, platelet inhibition,
sodium retention, and CNS dysfunction).
Patients at increased risk of NSAID-induced gastrointesti-
nal adverse effects (e.g., dyspepsia, peptic ulcer formation, and
bleeding) include the elderly, those with peptic ulcer disease,
coagulopathy, and patients receiving high doses of concurrent
corticosteroids. Nephrotoxicity is more common in the elderly,
patients with creatinine clearance values less than 50 mL/min,
and those with volume depletion or on diuretic therapy.
NSAIDs should be used with caution in patients with reduced
cardiac output due to sodium retention and in patients receiv-
ing antihypertensives, warfarin, and lithium.
NSAIDs are classied as nonselective (they inhibit COX-1
and COX-2) or selective (they inhibit only COX-2) based on
degree of cyclooxygenase inhibition. COX-2 inhibition is
responsible for anti-inammatory effects, while COX-1 inhi-
bition contributes to increased GI and renal toxicity associ-
ated with nonselective agents. Since the antiplatelet effect of
nonselective NSAIDs is reversible, concurrent use may reduce
Chisholm_Ch30.qxd 11/6/06 5:59 PM Page 494
CHAPTER 30 / PAIN MANAGEMENT 495
the cardioprotective effect of aspirin due to competitive inhibition
of COX-1. For this reason, administration of aspirin prior to the
NSAID is recommended.
40
The cardiovascular safety of the
COX-2 inhibitors has been questioned due to increased risk of
myocardial infarction and stroke seen in several trials.
4143
The
Food and Drug Administration (FDA) Committees on Arthritis
and Drug Safety and Risk Management convened in February
2005 to evaluate the published studies and manufacturer infor-
mation about the cardiovascular adverse events associated
with COX-2 inhibitors.
44
As a follow-up to the committees
recommendations, the FDA took regulatory action in April
2005, announcing that the increased risk of cardiovascular
events was likely a class effect of NSAIDs. A boxed warning
highlighting the potential for increased risk of cardiovascular
events and GI bleeding is now required for all prescription
nonselective NSAIDs and celecoxib. Stronger warnings about
these adverse events are also required on nonprescription
NSAIDs. As a result of the data and subsequent events, two
members of this class, rofecoxib and valdecoxib, have been
withdrawn from the market. Future COX-2 inhibitors and
nonselective NSAIDs will likely have to undergo cardiovascu-
lar safety studies before receiving FDA approval. When a
NSAID is needed in a patient with cardiovascular risk, the ben-
ets of therapy must outweigh the risk and the lowest effective
dose of NSAID is recommended.
Opioid Analgesics
Opioids are considered the agents of choice for the treatment
of severe acute pain and moderate to severe pain associated
with cancer.
45
For chronic pain their use was once highly con-
troversial; however, use of opioids in chronic pain is now gain-
ing acceptance.
46
Opioids may be classied by their activity at
the receptor site, usual pain intensity treated, and duration of
action (short- versus long-acting).
Selection and Dosing
The opioids exert their analgesic efcacy by stimulating opioid
receptors (, , and ) in the CNS. There is a wide variety of
potencies among the opioids, with some used for moderate
pain (codeine, hydrocodone, tramadol, and partial agonists) and
others reserved for severe pain (morphine and hydromor-
phone). Pure agonists (morphine) bind to receptors to pro-
duce analgesia that increases with dose without a ceiling effect.
Pure agonists are divided into three chemical classes: phenan-
threnes or morphinelike, phenylpiperidine or meperidinelike, and
diphenylheptane or methadonelike. Partial agonists/antagonists
(butorphanol, pentazocine, and nalbuphine) partially stimulate
the receptor and antagonize the receptors. This activity
results in reduced analgesic efcacy with a ceiling dose, reduced
side effects at the receptor, psychotomimetic side effects due to
antagonism, and possible withdrawal symptoms in patients
who are dependent on pure agonists.
Selection of the agent and route depend on individual
patient-related factors including severity of pain, individual
perceptions, weight, age, opioid tolerance, and concomitant
disease (renal or hepatic dysfunction). Since pure agonists are
pharmacologically similar, choice of agent may also be guided
by pharmacokinetic parameters and other drug characteristics.
Hepatic impairment can decrease the metabolism of most opi-
oids, particularly methadone, meperidine, pentazocine, and
propoxyphene. Furthermore, the clearance of meperdine,
propoxyphene, and morphine and their metabolites is reduced
in renal dysfunction. Patient Encounter: Part 2
Converting to Different Drugs and Adjusting
Doses
Two years following his diagnosis of lung cancer, BA has
been diagnosed as having bone metastases. Pain has been
controlled with the following medications: hydromorphone
(Dilaudid) 10 mg IV every hour and levorphanol
(Levodromoran) 10 mg orally every 4 hours. He is currently
receiving hydrochlorothiazide 25 mg daily, senna two
tablets twice daily, and docusate sodium 100 mg twice
daily. As the home care pharmacist, you are asked to con-
vert this patient to a morphine infusion.
Morphine equivalents (based on 10 mg parenteral mor-
phine) (Table 302):
Hydromorphone 1.5 mg is equivalent to 10 mg of morphine.
Levorphanol 4 mg is equivalent to 10 mg of morphine.
Based on BAs opioid requirement, recommend an initial infu-
sion rate (in milligrams per hour) of parenteral morphine.
Which adjuvant therapy could be considered for BA?
Recommend a monitoring plan for this patient.
How would you assess pain response?
TABLE 302. Equianalgesic Doses of Selected Opioids
Dose Equianalgesic to 10 mg
of Parenteral Morphine (mg)
Opioid Parenteral (mg) Oral (mg)
Mild-Moderate Pain
Codeine 120 200
Hydrocodone N/A 30
Oxycodone N/A 20
Meperidine (Demerol) 100 400
Propoxyphene (Darvon) N/A 65130
Moderate-Severe Pain
Morphine 10 30
Hydromorphone (Dilaudid) 1.5 7.5
Oxymorphone 1 N/A
Levorphanol 2 4
Fentanyl (Duragesic) 0.10.2 N/A
a
Methadone (Dolophine) 10
b
35
b
a
Transdermal: 100 mcg/h = 24 mg/h of IV morphine.
b
Dosage calculations when converting from morphine to methadone are
not linear. The equianalgesic dose of methadone will decrease progres-
sively as the morphine equivalents increase (see Table 30-4).
Data from references 26, 45, 49, and 51.
Chisholm_Ch30.qxd 11/6/06 5:59 PM Page 495
496 SECTION 5 / NEUROLOGIC DISORDERS
Table 303 provides a summary of opiate side effects, but sev-
eral drugs warrant further discussion. Normeperidine, the active
metabolite of meperidine, can produce tremors, myoclonus,
delirium, and seizures. Due to the potential for accumulation of
normeperidine, meperidine should not be used in the elderly,
those with renal impairment, in patients using patient-controlled
analgesia devices, or for more than 1 to 2 days of continuous
dosing with intermittent dosing. Propoxyphene also has an
increased risk of seizures and cardiac conduction abnormalities
and should be avoided in the elderly. Despite its popularity,
propoxyphene has proven to be no more effective than aceta-
minophen, aspirin, or codeine alone.
18
Methadone is unique
among the opiates since is it has several mechanisms ( agonist,
NMDA receptor antagonist, and inhibition of reuptake of sero-
tonin and norepinephrine) that makes it an interesting choice
for chronic pain. The long half-life of methadone (30 hours)
permits extended dosing intervals; however, the potential for
accumulation with repeated dosing often results in challenging
dose conversions. Tramadol is a synthetic opioid with a dual
mechanism of action ( agonist and inhibition of serotonin and
norepinephrine reuptake), and efcacy and safety similar to that
of equianalgesic doses of codeine plus acetaminophen.
Tramadol has been evaluated in several types of neuropathic
pain and may have a place in the treatment of chronic pain.
Tramadol is associated with an increased risk of seizures in
patients with a seizure disorder, those at risk for seizures, and
those taking medications that can lower the seizure threshold.
Doses greater than 500 mg have also been associated with
seizures. Use of tramadol with other serotonergic drugs (e.g.,
selective serotonin reuptake inhibitors [SSRIs]) may precipitate
serotonin syndrome. While originally thought to be nonhabit
forming, dependence may occur with tramadol.
About 70% of individuals will experience signicant analge-
sia from 10 mg/70 kg of body weight of intravenous morphine
or its equivalent.
18
For severe pain in opiate-nave patients, a
usual starting dose is 5 to 10 mg of morphine every 4 hours. In
the initial stages of severe pain, medication should be given
around the clock. Rescue doses should be made available in
doses equivalent to 10% to 20% of the total daily opioid
requirement and administered every 2 to 6 hours if needed.
Alternatively one-sixth of the total daily dose or one-third or
the 12-hourly dose may be used. Doses should be titrated based
on the degree of pain. One method involves adjustment of the
maintenance dose based on the total 24-hour rescue dose
requirement. Utilizing dose escalation, doses should be
increased by 50% to 100% or 30% to 50% of the current dose,
for those in severe and moderate pain, respectively. Once pain relief
is achieved, and if treatment is necessary for more than a few days,
conversion to a controlled-release or long-acting opioid should be
made with an equal amount of agent. Several sustained-release
products are available containing morphine, oxycodone, and
fentanyl. Some clinicians will reduce the total daily dose of the
long-acting dosage form by 25% when initiating a sustained-
release product to reduce the likelihood of oversedation. The
dose of a pure agonist is limited only by tolerability to side
effects. Tolerance may develop to analgesic effects necessitating
increasing doses to achieve the same level of pain relief. Physical
dependence will also occur with long-term use of opioids.
However, addiction or psychological dependence is unlikely in
legitimate pain patients unless there are predisposing risk fac-
tors. Pain patients who are undertreated may appear to be drug-
seeking (pseudoaddiction); however, effective pain management
resolves the behaviors. When opioids are used for chronic pain,
use of informed consent for chronic opioid therapy and med-
ication management agreements or pain contracts may be
appropriate to monitor the use (prescribing and dispensing) of
controlled substances.
Opioids may be administered in a variety of routes
including oral (tablet and liquid), sublingual, rectal, trans-
dermal, transmucosal, intravenous, subcutaneous, and
intraspinal. While the oral and transdermal routes are most com-
mon, the method of administration is based on patient needs
(severity of pain) and characteristics (swallowing difculty and
preference). Oral opioids have an onset of effect of 45 minutes,
TABLE 303. Managing Opioid Side Effects
Adverse Effects Drug Treatment/Management
Excessive sedation Reduce dose by 25% or
increase dosing interval
Constipation Casanthranol-docusate 1 cap at
bedtime or twice daily; senna
12 tabs at bedtime or twice
daily; bisacodyl 510 mg daily +
docusate 100 mg twice daily
Nausea and vomiting Prevention: hydroxyzine 25100 mg
(PO/IM) every 46 hours as
needed; diphenhydramine 2550 mg
(PO/IM) every 6 hours as needed;
ondansetron 4 mg IV or 16 mg PO
Treatment: prochlorperazine 510 mg
(PO/IM) every 34 hours as
needed or 25 mg per rectum twice
daily; ondansetron 48 mg IV every
8 hours as needed
Gastroparesis Metoclopramide 10 mg (PO/IV) every
68 hours
Vertigo Meclizine 12.525 mg PO every 6 hours
as needed
Urticaria/itching Hydroxyzine 25100 mg (PO/IM) every
46 hours as needed;
diphenhydramine 2550 mg (PO/IM)
every 6 hours as needed
Respiratory depression Mild: Reduce dose by 25%
Moderate -severe: naloxone 0.42 mg
IV every 23 minutes (up to 10 mg)
for complete reversal; 0.10.2 mg
IV every 23 minutes until desired
reversal for partial reversal;may need
to repeat in 12 hours depending
on narcotic half-life
CNS irritability Discontinue opioid; treat with
benzodiazepine
CNS, central nervous system; IM, intramuscular; IV, intravenous; PO, orally.
Data from references 27, 45, and 49.
Chisholm_Ch30.qxd 11/6/06 5:59 PM Page 496
CHAPTER 30 / PAIN MANAGEMENT 497
so intravenous or subcutaneous administration may be pre-
ferred if more rapid relief is desired. Intramuscular injections
are not recommended because of pain at the injection site and
wide uctuations in drug absorption and peak plasma concen-
trations achieved. More invasive routes of administration such
as PCA and intraspinal (epidural and intrathecal) are primarily
used postoperatively, but may also be used in refractory chronic
pain situations. PCA delivers a self-administered dose via an
infusion pump with a preprogrammed dose, minimum dosing
interval, and maximum hourly dose. Morphine, fentanyl, and
hydromorphone are commonly administered via PCA pumps
by the intravenous route, but less frequently by the subcuta-
neous or epidural route.
Epidural analgesia is frequently used for lower extremity
procedures and pain (e.g., knee surgery, labor pain, and some
abdominal procedures). Intermittent bolus or continuous
infusion of preservative-free opioids (morphine, hydromor-
phone, or fentanyl) and local anesthetics (bupivacaine) may be
used for epidural analgesia. Opiates given by this route may
cause pruritus that is relieved by naloxone. Adverse effects
including respiratory depression, hypotension, and urinary
retention may occur. When epidural routes are used in narcotic-
dependent patients, systemic analgesics must also be used to
prevent withdrawal since the opioid is not absorbed and
remains in the epidural space. Doses of opioids used in
epidural analgesia are 10 times less than intravenous doses, and
intrathecal doses are 10 times less than epidural doses (i.e., 10
mg of IV morphine is equivalent to 1 mg epidural morphine
and 0.1 mg of intrathecally administered morphine).
45
Combination Analgesics
Combinations of opioids and nonopioids often result in
enhanced analgesia and lower dose of each. Combination anal-
gesics are frequently used in moderate pain. However, in severe
pain, the nonopioid component reaches maximum dosage,
and thus the usefulness of nonopioids in this situation is lim-
ited. Additionally, the combination products are short-acting
and often not suitable for chronic therapy. Single agents offer
greater dosing exibility than combination products.
Opioid Allergy
True narcotic allergies are rare and should not be confused
with pruritus associated with opiate use. Cross-sensitivity
between morphinelike, meperidinelike, and methadonelike
agents is unlikely. Therefore, when an individual is allergic to
one drug in a chemical class of opioids, it is reasonable to select
an agent in another chemical class. For the purpose of drug
selection in patients with allergies, mixed antagonists should
be treated as morphinelike agents.
Tapering of Opioids
Tapering of opioids may be necessary once the painful situa-
tion has resolved in patients receiving doses >160 mg/d of
oral morphine (or the equivalent) or in those with prolonged
opioid use. In these situations the dose should be reduced by
15% to 20% each day to avoid withdrawal symptoms.
Managing Opioid Side Effects and Drug Interactions
Side effects common to all opioids include sedation, hallucina-
tions, constipation, nausea and vomiting, urinary retention,
myoclonus, and respiratory depression. In terms of medication
management, the most frequent are sedation, nausea, and con-
stipation. Sedation and nausea are common when initiating
therapy and when increasing doses. Nausea can be prevented
with a centrally-acting antiemetic (see Table 203). Sedation
usually improves with continued therapy but may become
intractable at high doses, and stimulants may be needed.
Respiratory depression is a serious adverse effect, and usually
occurs after acute administration in opioid-nave patients.
Tolerance to respiratory depression develops rapidly with
repeated doses and is rarely a clinically signicant problem in
pain patients, even those with respiratory impairment.
Constipation is a signicant adverse effect to which tolerance
does develop, and prophylaxis with stimulant laxatives (e.g.,
senna or bisacodyl) and stool softeners, such as docusate, is
recommended.
Codeine, hydrocodone, morphine, methadone, and oxy-
codone are substrates of the cytochrome P-450 isoenzyme
CYP2D6.
47
Inhibition of CYP2D6 results in decreased analge-
sia of codeine and hydrocodone due to decreased conversion to
the active metabolites (e.g., morphine and hydromorphone,
respectively) and increased effects of morphine, methadone,
and oxycodone. Methadone is also a substrate of CYP3A4, and
its metabolism is increased by phenytoin and decreased by
cimetidine. CNS depressants may potentiate the sedative
effects of opiates.
Opioid Rotation
Opioid rotation is the switch from one opioid to another to
achieve a better balance between analgesia and treatment-limiting
adverse effects. This practice is often used when escalating doses
(greater than 1 g of morphine per day) become ineffective. In
some settings opioid rotation is utilized routinely to prevent
the development of analgesic tolerance.
48
Equianalgesic Dosing of Opioid Analgesics
Conversion from one dosage form to another or from one opi-
oid to another may be necessary in situations such as ineffective
pain control, emergence of side effects, change in patient status,
and in formulary restrictions. Equianalgesic doses should be
used when converting from one opioid to another. Clinicians
should be familiar with the equianalgesic dosing and conver-
sion strategies to avoid analgesic failure. Equianalgesic tables
serve as a guide for selection of the dosage of the new opioid,
but have limitations, as they are often based on single-dose
studies and clinical observations.
32
Opioid potency is compared
using a reference standard of 10 mg of parenteral morphine.
Switching from one dosage form to another of the same opioid
(i.e., IV to PO) is relatively simple. The current total daily dose
is calculated and the total of the new dosage form is determined
using a ratio of the equianalgesic doses. This result is then
adjusted based on the usual dosing frequency of the new form.
Chisholm_Ch30.qxd 11/6/06 5:59 PM Page 497
498 SECTION 5 / NEUROLOGIC DISORDERS
When converting to a sustained-release form of the same opioid,
dosage may be reduced by 25% to avoid initial sedation; how-
ever, the specic product literature should also be consulted.
The rst step in an opioid rotation is to calculate the
patients total daily dose of opioid based on the regularly sched-
uled dose and the total amount of rescue dose needed in 24
hours. This total is then converted to morphine dosing equiva-
lents using equianalgesic doses (see Table 302). The total daily
morphine dose is then used to calculate the daily dose of the
new opioid using dosing equivalents from an equianalgesic
table. Since cross-tolerance may not be complete between opi-
oids, some references suggest that the calculated equianalgesic
dose be reduced by 25% to 50%.
49
If the opioid switch is due to
uncontrolled pain, a dosage reduction may not be needed. The
equianalgesic dose may need to be reduced more in the med-
ically frail and when converting to methadone.
50
Using the
commonly cited equianalgesic dose of morphine to methadone
(10 mg morphine:10 mg methadone), methadone doses should
be reduced by 75% to 80%. However, this ratio is not applica-
ble even in patients tolerant to low doses of morphine.
51
Methadone appears to be much more potent than once
believed, and morphine:methadone ratios vary according to the
total dose of morphine taken at the time of making the conver-
sion to methadone (Table 304).
52,53
Conversion to methadone
is a complex process, and several different strategies have been
proposed including a switch of the entire dose in one day or a
gradual conversion over 3 days.
Adjuvant Agents for Chronic Pain
The role of NSAIDs and opioids in chronic nonmalignant pain
has been discussed; however, a review of adjuvant agents for
chronic pain, particularly neuropathic pain, is warranted.
Adjuvant analgesics are drugs that have indications other than
pain but are useful as monotherapy or in combination with
nonopioids and opioids. Common adjuvants include antiepilep-
tic drugs (AEDs), antidepressants, antiarrhythmic drugs, local
anesthetics, topical agents (e.g., capsaicin), and a variety of
miscellaneous drugs (e.g., NMDA antagonists, clonidine, and
muscle relaxants).
There is little consensus as to the optimal management of
neuropathic pain, because much of the evidence for treatment
effectiveness consists of anecdotal reports or poorly designed
trials. Published guidelines have been suggested for the general
management of neuropathic pain.
54
Suggestions for rst-line
therapy include gabapentin, lidocaine patch, or tricyclic antide-
pressants (TCAs) (Table 305).
5458
Newer antidepressants,
such as the SSRIs, have fewer side effects but appear to be less
effective than the TCAs for neuropathic pain. However, sero-
tonin-norepinephrine reuptake inhibitors (SNRIs) (e.g., dulox-
etine and venlafaxine) have been used successfully for painful
DPN. A stepwise approach is suggested for managing the
patient with neuropathic pain, beginning with the least invasive
effective therapeutic choice and proceeding to the rational use
of multiple drug regimens. To guide the choice of pharmaco-
logic agents, patients may be identied as candidates for AEDs,
TCAs, or opioids based on the presence of peripheral or central
nerve pain and description of symptoms (see Fig. 302). Choice
of agent may also depend on dosing frequency and comorbidi-
ties. Data on combination therapy are lacking, and the use of
combined treatment is empirical based on additive therapeutic
benet. Scheduled medication regimens instead of as needed
TABLE 304. Methadone Dose Conversions
Total Daily Dose Morphine:
Oral Morphine Methadone Factor
<100 mg 3:1
3 mg morphine: 1 mg methadone
101300 mg 5:1
301600 mg 10:1
601800 mg 12:1
8011,000 mg 15:1
>1,000 mg 20:1
Data from reference 53 with permission.
TABLE 305. Selected Adjuvant Analgesics and Suggested
Dosing
FDA-Approved
Agent Dosing Guidelines Indication
Amitriptyline 1025 mg at bedtime with
(Elavil) weekly increments to a
target dose of 25150 mg
of amitriptyline or an
equivalent dose of another
TCA
Duloxetine 60 mg daily DPN
(Cymbalta)
Gabapentin Initially, 300 mg three times PHN
(Neurontin) daily up to a maximum
of 3,600 mg daily, in
divided doses
a
Pregabalin DPN: Initially, 50 mg three DPN
(Lyrica) times daily; may be and PHN
increased to 100 mg
three times daily within
1 week based on efcacy
and tolerability
a
PHN: Initially 75 mg twice
daily or 50 mg three times
daily; may be increased
to 100 mg three times
daily within 1 week based
on efcacy and tolerability
a
Lidocaine 5% Up to three patches may be PHN
(Lidoderm applied directly over the
patch) painful site once daily;
patches are applied using
a regimen of 12 hours on
and 12 hours off
a
Dosing for creatinine clearance of 60 mL/min or greater.
DPN, diabetic peripheral neuropathy; PHN, post-herpetic neuralgia;
TCA, tricyclic antidepressant.
Data from references 5458.
Chisholm_Ch30.qxd 11/6/06 5:59 PM Page 498
CHAPTER 30 / PAIN MANAGEMENT 499
dosing should be employed when treating chronic pain, and
the effectiveness of therapy should be reassessed regularly. If
patients are managed on a multiple drug regimen and changes
are indicated, changing only one drug at a time is suggested.
Topical agents (e.g., capsaicin) may be added to a regimen to
reduce the oral medication load, particularly if adverse effects
are a problem or if pain is not relieved.
Complementary and Alternative Medicine
Complementary and alternative medicine (CAM) is a term
used to encompass a variety of therapies (e.g., acupuncture,
chiropractic, botanical and nonbotanical dietary supplements,
and homeopathy) not typically taught in medical and allied
health schools. Painful conditions are among the most common
reasons individuals seek relief from CAM. In a recent survey,
neck pain, joint pain, arthritis, and headache were among the top
ten reasons for use of CAM, and low back pain ranked the num-
ber one reason for CAM therapies. A variety of dietary supple-
ments have been suggested for painful conditions, such as S-
adenosylmethionine (SAM-e), ginger, sh oil, feverfew, -linoleic
acid, glucosamine, and chondroitin. Of these, glucosamine and
chondroitin are the most popular and have the most evidence
of efcacy. Glucosamine in doses of 1,500 mg/d is effective in
reducing pain of osteoarthritis by repair of cartilage and is rec-
ommended by the American Pain Society.
OUTCOME EVALUATION
Individualize treatment goals at the beginning of treatment.
Utilize information obtained during the pain interview to cre-
ate goals that are consistent with the patients expectations.
Prevention, reduction, or elimination of pain are important
goals for treatment of acute pain. With chronic pain, elimi-
nation of pain may not be possible, and goals may focus on
improvement or maintenance of functional capacity and
quality of life. Thus, for example, pain goals may include
pain scale less than 3, be able to play a game with grand-
children, or be able to knit again. Assess patients periodi-
cally, depending on the method of analgesia and pain condi-
tion, for achievement of pain goals. Evaluate the patient for
the presence of adverse drug reactions, drug allergies, and
drug interactions.
ABBREVIATIONS
AED: Antiepileptic drug
AIDS: acquired immunodeciency syndrome
AMPA: -amino-3-hydroxy-5-methylisoxazole-4-propionic
acid
APAP: acetaminophen
CAM: complementary and alternative therapy
CNS: central nervous system
COX: cyclooxygenase
CRPS: complex regional pain syndrome
CYP: cytochrome P-450 isoenzyme
DPN: diabetic peripheral neuropathy
FDA: Food and Drug Administration
GABA: -aminobutyric acid
GI: gastrointestinal
HIV: human immunodeciency virus
IV: intravenous
IM: intramuscular
JCAHO: Joint Commission on Accreditation of Healthcare
Organizations
NMDA: N-methyl-D-aspartate
NSAID: nonsteroidal anti-inammatory drug
PAINAD: Pain Assessment in Advanced Dementia (tool)
PCA: patient-controlled analgesia
PHN: post-herpetic neuralgia
PO: oral
PQRST: Palliative/precipitating, Quality, Radiation, Severity, and Time
SAM-e: S-adenosylmethionine
SNRI: serotonin-norepinephrine reuptake inhibitor
SSRI: selective serotonin reuptake inhibitor
TCA: tricyclic antidepressant
TENS: transcutaneous electrical nerve stimulation
VAS: visual analog scale
WHO: World Health Organization
Reference lists and self-assessment questions and answers are
available at (insert web address here).
KEY REFERENCES AND READINGS
American Geriatrics Society Panel on Persistent Pain in Older
Persons. The management of persistent pain in older persons. J
Am Geriatr Soc 2002;50:120.
Patient Care and Monitoring
1. Identify the source of pain.
2. Assess the level of pain using a pain intensity
scale.
3. Base the initial choice of analgesic on the severity and
type of pain, as well as on the patients medical condi-
tion and concurrent medications.
4. Use the least potent oral analgesic that provides ade-
quate pain relief and causes the fewest side effects.
5. Titrate the dose to one that achieves an adequate level
of pain control.
6. Use a dosing schedule versus as-needed dosing.
7. Assess the patient for analgesic effectiveness and for side
effects at each visit or more frequently, depending on
the acuity of the patients condition.
8. Avoid excessive sedation.
9. Adjust the route of administration if the patient is unable
to take oral medications.
10.Use equianalgesic doses as a guide when switching
opioids.
Chisholm_Ch30.qxd 11/6/06 5:59 PM Page 499
500 SECTION 5 / NEUROLOGIC DISORDERS
American Pain Society. Principles of Analgesic Use in the Treatment
of Acute Pain and Cancer Pain. 5th ed. Glenview, IL: American
Pain Society, 2003: 1341.
Clinical Practice Guideline, Cancer Pain Management. U.S.
Department of Health and Human Services, Agency for
Health Care Policy and Research. AHCPR Pub. Rockville,
MD: 1994. Available at: http://www.ncbi.nlm.nih.gov/books/
bookres.fcgi/ hstat6/ f37_capcf4.gif. Accessed January 10,
2006.
Dworkin RH, Backonja M, Rowbotham MC, et al. Advances in neu-
ropathic pain: diagnosis, mechanisms, and treatment recom-
mendations. Arch Neurol 2003;60:15241534.
Joint Commission on Accreditation of Healthcare Organizations.
Pain Assessment and Management an Organizational Approach.
Oakbrook Terrace, IL: JCAHO,2000:16.
Woolf CJ. Pain: moving from symptom control toward mechanism-
specic pharmacologic management. Ann Intern Med 2004;140:
441451.
Chisholm_Ch30.qxd 11/6/06 5:59 PM Page 500

You might also like