Definition and pathogenesis of chronic pain

INTRODUCTION Pain is one of the most common and debilitating patient complaints,
affecting individual patients, their friends and families, the work force, and society in
general.
Research efforts in understanding pain range from the molecular biology of nociceptive
pathways to the psychosocial aspects that influence the experience of pain. Although such
studies have resulted in significant strides in pain management and quality of life for
patients with persistent pain, the evaluation and treatment of pain remains suboptimal.
An overview of the definition, classification, and pathogenesis of chronic pain is presented
here. The evaluation of patients presenting with chronic pain, the general therapeutic
principles of chronic pain, and specific pain syndromes are discussed separately.
(See "Evaluation of chronic pain in adults".)
EPIDEMIOLOGY Over 100 million Americans suffer chronic pain [1,2] and roughly 63
percent of pain sufferers seek help from their primary care clinicians [3]. Pain accounts for
20 percent of outpatient visits and 12 percent of all prescriptions [4]. Patients with
symptoms of chronic pain are seen by clinicians in multiple clinical settings. Most patients
who present with pain complaints rate their symptoms as moderate to severe [5,6]. One
survey from 2010 estimated that 19 percent of adults in the United States report constant
or frequent pain persisting for at least three months [7].
Persistent pain often causes functional impairment and disability, psychological distress
(anxiety, depression), and sleep deprivation [8]. Almost 80 percent of chronic pain patients
report that pain disrupts their activities of daily living, and two-thirds indicate that pain has
negatively impacted personal relationships [9].
Pain is the most common cause of long-term disability, with lost work days in the United
States estimated at more than 50 million days per year [10]. The annual cost of untreated
or undertreated pain to taxpayers and employers has been calculated at over $100 billion
per year, in direct and indirect expenses [4]. The use and misuse of opioids for
management of chronic pain is a major concern, with problems arising from their multiple
adverse side effects including drug-dependency, from drug diversion, and from undertreatment of chronic pain symptoms for fear of narcotic abuse. Chronic pain is thus a major
medical and social issue [11].
PAIN-RELATED DEFINITIONS Acute pain is a vital, protective mechanism that permits
us to live in an environment fraught with potential dangers [12]. Certain stimuli are
associated with danger that should be avoided, even at some cost, to prevent tissue
damage.
Pain can be considered in two broad categories: adaptive and maladaptive. Adaptive pain
contributes to survival by protecting the organism from injury and/or promoting healing

when injury has occurred. Maladaptive or chronic pain is pain as disease and represents
pathologic functioning of the nervous system.
Pain definition Pain has been variously defined. A commonly used definition describes
pain as an unpleasant sensory and emotional experience associated with actual or
potential tissue damage or described in terms of such damage [13]. A revised definition
identifies pain as "a somatic perception containing: (1) a bodily sensation with qualities like
those reported during tissue-damaging stimulation, (2) an experienced threat associated
with this sensation, and (3) a feeling of unpleasantness or other negative emotion based
on this experienced threat" [14].
Chronic pain Chronic pain has been defined as pain which lasts beyond the ordinary
duration of time that an insult or injury to the body needs to heal. An argument has been
made that the term "persistent pain" should be used in lieu of "chronic pain" [15].
Alternative definitions are based on a specified duration of pain, although there is
discrepancy on what that duration should be.
The International Association for the Study of Pain (IASP) definition addresses both
duration and appropriateness, defining chronic pain as pain without apparent biologic
value that has persisted beyond the normal tissue healing time (usually taken to be
three months) [16].
The American College of Rheumatology (ACR) defines chronic pain as widespread
or regional pain for at least three months [17]. ACR criteria for chronic widespread
pain include all of the following: pain present for at least three months, pain in the left
and right sides of the body, pain above and below the waist, and the presence of axial
skeletal pain (cervical spine anterior chest, thoracic spine, or low back).
The Diagnostic and Statistical Manual of Mental Disorders, 4th edition (DSM-IV)
defines chronic pain as persistent pain for six months [18].
The American Society of Anesthesiologists defines chronic pain as pain of any
etiology not directly related to neoplastic involvement, extending in duration beyond
the expected temporal boundary of tissue injury and normal healing and adversely
affecting the function or well-being of the individual [19].
Pain duration shorter than six months but present beyond the "expected healing period"
has been termed "subacute pain" by some clinicians.
Pain descriptor terminology The following terms are commonly used descriptors of
altered sensation [13]:
Hyperalgesia Increased response to a stimulus that normally is painful.
Hypoalgesia Diminished response to a normally painful stimulus.
Analgesia Absence of pain in response to stimulation that normally is painful.
Hyperesthesia Increased sensitivity to stimulation, excluding the special senses.

Hypesthesia Diminished sensitivity to stimulation, excluding the special senses.

Dysesthesia An unpleasant abnormal sensation, whether spontaneous or
evoked.
Paresthesia An abnormal sensation, whether spontaneous or evoked.
Allodynia Pain resulting from a stimulus (such as light touch) that does not
normally elicit pain.
Types of pain Pain is often categorized as being either nociceptive or neuropathic.
Other pain schemes define additional categories (psychogenic or muscle pain) [20,21].
The primary distinction between nociceptive and neuropathic pain has implications for
evaluation and treatment decisions.
Nociceptive pain A nociceptor is a nerve fiber preferentially sensitive to a noxious
stimulus or to a stimulus that would become noxious if prolonged. Nociceptive pain is the
perception of nociceptive input, usually due to tissue damage (eg, postoperative pain).
Nociceptive pain is further subdivided into somatic and visceral pain. Somatic pain arises
from injury to body tissues. It is well localized but variable in description and experience.
Visceral pain is pain arising from the viscera mediated by stretch receptors. It is poorly
localized, deep, dull, and cramping (eg, pain associated with appendicitis, cholecystitis, or
pleurisy).
One classification system of pain further subdivides nociceptive pain as musculoskeletal
pain, inflammatory pain (eg, inflammatory arthropathies, postoperative pain, tissue injury,
infection), or mechanical/compressive pain (eg, low back pain, neck pain, visceral pain
from expanding tumor masses) [22].
Neuropathic pain Neuropathic pain arises from abnormal neural activity secondary to
disease, injury, or dysfunction of the nervous system. It commonly persists without
ongoing disease (eg, diabetic neuropathy, trigeminal neuralgia, or thalamic pain
syndrome). Neuropathic pain is further subdivided as follows:
Sympathetically mediated pain (SMP) is pain arising from a peripheral nerve lesion
and associated with autonomic changes (eg, complex regional pain syndrome I and
II, formerly known as reflex sympathetic dystrophy and causalgia) [23,24].
(See "Complex regional pain syndrome in adults: Pathogenesis, clinical
manifestations, and diagnosis".)
Peripheral neuropathic pain is due to damage to a peripheral nerve without
autonomic change (eg, postherpetic neuralgia, neuroma formation).
Central pain arises from abnormal central nervous system (CNS) activity (eg,
phantom limb pain, pain from spinal cord injuries, and post-stroke pain).
Neuropathy is also described as mononeuropathy if one nerve is affected,
mononeuropathy multiplex if several nerves in different areas of the body are involved, and
polyneuropathy if symptoms are diffuse and bilateral.

Pain taxonomy The International Association for the Study of Pain (IASP) has
developed a taxonomy for the classification of pain [13]. This classification system
identifies five axes:
Axis I: Anatomic regions
Axis II: Organ systems
Axis III: Temporal characteristics, pattern of occurrence
Axis IV: Intensity, time since onset of pain
Axis V: Etiology
The IASP Classification of Chronic Pain is compatible with the International Classification
of Diseases (ICD 9 and ICD 10) but provides for more detailed identification of various
chronic pain syndromes and major acute pain syndromes.
Simpler schemes often are used in the day to day practice of pain medicine. One scheme
identifies eight unidimensional subtypes or classifications for pain [25]:
Pain location (eg, low back pain, headache)
Pain duration (eg, acute, subacute, chronic) (see 'Chronic pain' above)
Pain origin (eg, nociceptive or neuropathic) (see 'Types of pain' above)
Diagnosis (eg, cancer pain, sickle cell pain, postherpetic neuralgia)
(see 'Pathogenesis of pain' below)
Body system (eg, myofascial, rheumatic, neurologic, vascular) [26]
Pain severity (eg, mild, moderate, or severe)
Pain mechanism(s) (eg, peripheral sensitization, disinhibition, or central
sensitization) [27] (see 'Mechanisms for persistent pain' below)
Treatment responsiveness (eg, opioid-responsive pain, opioid poorly responsive
pain)
Two of these classifications may be combined (eg, chronic noncancer pain).
PATHOGENESIS OF PAIN Pain sensation begins in the periphery of the nervous
system. Pain stimuli are sensed by specialized nociceptors that are the nerve terminals of
the primary afferent fibers. The pain signal is then transmitted to the dorsal horn of the
spinal column and transmitted through the central nervous system (CNS) where it is
processed and interpreted in the somatosensory cerebral cortex (figure 1).
Multiple ascending pathways may be involved in relaying nociceptive information to the
brain, including spinocervical, spinobulbar, spinopontine, spinomesencephalic, spinodiencephalic (containing spinothalamic tracts), and spinotelencephalic pathways. The
majority of the wide dynamic range and nociceptive specific neurons project contralaterally
within the spinal cord and ascend within the anterolateral quadrant, forming the
spinothalamic tract which synapses in the thalamus (figure 2). Neurons from the thalamus

project to multiple brain areas in the primary and secondary somatosensory cortex,
cingulate cortex, prefrontal cortex, insular cortex, amygdala, and the cerebellum.
Four physiologic processes are associated with pain: transduction, transmission,
modulation, and perception.
Transduction refers to the conversion of a noxious stimulus (thermal, mechanical,
or chemical) into electrical activity in the peripheral terminals of nociceptor sensory
fibers.
Transmission refers to the passage of action potentials from the peripheral terminal
along axons to the central terminal of nociceptors in the central nervous system.
Conduction is the synaptic transfer of input from one neuron to another.
Modulation refers to the alteration (eg, augmentation or suppression) of sensory
input.
Perception refers to the "decoding"/interpretation of afferent input in the brain that
gives rise to the individual's specific sensory experience.
Nociceptors Nociceptors are a highly-specialized subset of primary sensory neurons
that respond only to pain stimuli. They are categorized by the kind of stimulation they
respond to and the nature of their response [28]. Most noxious stimuli activate a variety of
nociceptor types in the affected area. Their signals sum to produce the nociceptive input,
leading to the subjective sense of pain.
Myelinated nociceptors are relatively fast-conducting A-delta fibers. Some respond
readily to heat (mechanothermal receptors, MTRs); others are high-threshold
mechanoreceptors (HTMs). The discharge intensity is linearly related to the degree of
the stimulus [29]. A-delta fibers are responsible for the first (immediate) sharp pain.
Unmyelinated C fibers constitute the large majority of peripheral nociceptors. Most
are classified as C-polymodal nociceptors (C-PMN), responding to thermal,
mechanical, and chemical stimuli. These are slow-conducting primary afferents that
recover from fatigue more slowly than those of A-delta nociceptors. C fibers mediate
delayed and longer-lasting pain, typically characterized as dull.
Nociceptors also vary in their threshold to response and their rate of firing to the dorsal
horn of the spinal cord. Wide dynamic range (WDR) nociceptors respond to a continuum of
stimuli, such as moderate warmth through noxious high temperatures. Other nociceptors
respond only to noxious stimuli (nociceptor specific, NS).
Nociceptive afferents are classified as peptidergic or nonpeptidergic. Peptidergic cells
express substance P, and/or calcitonin gene-related peptide or somatostatin as well as
tyrosine kinase receptor A and/or TRPV1 and project centrally to lamina I and the outer
lamina II of the dorsal horn. Nonpeptidergic cells express the purinergic ligand-gated ion
channel P2X3 and project centrally to the inner lamina II of the dorsal horn.

Sodium channel subunits in the cell membrane of nociceptive neurons control the
generation of nerve impulses that travel from dorsal root ganglia to the brain. Genes have
been identified which code differing protein isoforms of the sodium channel [30]. One of
these genes, SCN9A, encodes a specific sodium channel (Na(v)1,7) that is found in
nociceptive and sympathetic ganglion neurons, and appears to modulate the pain signal
[31]. This finding suggests an intriguing opportunity to develop pharmacologic agents,
targeted to the Na(v)1,7 sodium channel, which might inhibit pain sensation with minimal
other physiologic effects.
CNS processing Signal transfer from nociceptors to neurons in the dorsal horn of the
spinal cord that project to the brain is mediated either by direct monosynaptic contact or
through interneurons, which may be either excitatory or inhibitory [12]. Counterirritation
and low-threshold afferent inputs (transcutaneous electrical nerve stimulation or spinal
cord stimulation), used to modulate pain in patients with chronic pain syndromes, activate
inhibitory mechanisms but their effect is generally small and short lasting.
A small fraction of the sensory input that enters the spinal cord is transmitted via action
potentials from the neurons in the dorsal horn to the thalamus. The thalamus relays this
information to the cortex.
Sensory processing is controlled through local segmental circuits in the spinal cord and by
descending inhibitory and facilitatory signals arising from the brain [12]. The CNS is
equipped with a descending or modulatory system which acts to alter afferent nociceptive
information. Several regions of the brain are involved in this activity, including the
somatosensory cortex, the hypothalamus, the periaqueductal gray matter, and areas in the
pons. Prefrontal cortex and anterior cingulate cortex circuitry may also dampen nociceptive
input and cause analgesia. Descending fibers from these structures pass through the
dorsolateral funiculus (DLF) and synapse with nociceptive neurons in the dorsal horn of
the spinal cord. These fibers may interact with the opioid system, noradrenergic system,
and serotonergic system, and can significantly inhibit responses to noxious stimuli.
Additionally, descending facilitatory pain pathways are also present.
MECHANISMS FOR PERSISTENT PAIN Multiple mechanisms promote or facilitate
persistent or chronic pain. These include peripheral sensitization, central sensitization,
ectopic excitability, structural reorganization/phenotypic switch of neurons, primary
sensory degeneration, and disinhibition. Peripheral and central sensitization are the major
causes of pain hypersensitivity after injury.
Peripheral sensitization Tissue inflammation may result in changes in the chemical
environment of the peripheral terminal of nociceptors. Damaged cells may release
intracellular contents and synthesize substances including cytokines, chemokines,
bradykinin, histamine, prostaglandins, and growth factors. Released cellular ions create a
more acidic environment.

Inflammatory cells are recruited to the site of damage, in part due to the attractant
properties of proinflammatory mediators such as leukotriene B4 [LTB4] [32]. Some of
these proinflammatory mediators directly activate the nociceptor terminal and produce pain
(nociceptor activators); others sensitize the terminal so that it becomes hypersensitive to
subsequent stimuli (nociceptor sensitizers) [12].
The release of adenosine triphosphatase by injured cells, for example, causes
immediate activation and results in immediate detection of tissue damage [28].
Transient receptor potential V1 (TRPV1) channels expressed by nociceptors may
produce pain some time after injury [33]. These channels are calcium-permeable
nonselective cation channels gated by heat, low pH, or chemical mediators
(endovanilloids). Activation of mitogen-activated protein kinase (MAPK) signaling in
TRPV1 may contribute to hyperresponsiveness of peripheral nociceptors (peripheral
sensitization). In addition to producing inflammation and inducing synthesis of several
nociceptor sensitizers, IL-1beta also rapidly and directly activates nociceptors to
generate action potentials and induce pain hypersensitivity [34].
Central sensitization Central sensitization amplifies the synaptic transfer from the
nociceptor terminal to dorsal horn neurons [12]. Initial sensitization to synaptic transfer is
activity-dependent, triggered by nociceptor input into the spinal cord. Later transcriptional
changes in the molecular machinery of the dorsal cell sustain the sensitization beyond the
initiating stimulus (ie, transcription-dependent) [35,36]. Thus, previously subthreshold
synaptic inputs to nociceptive neurons now generate an augmented action potential
output.
The glutamate-activated N-methyl-D-aspartic acid (NMDA) receptor is integral to this
central sensitization process [12,37]. During central sensitization, the NMDA receptor is
phosphorylated, which increases its distribution in the synaptic membrane and its
responsiveness to glutamate. Increased responsiveness to glutamate occurs by removal
of a normal voltage-dependent magnesium ion block of the NMDA channel, increasing the
time the channel is open. The increase in excitability of the dorsal horn cell means that it
can be activated by normally subthreshold inputs, with increased response to
suprathreshold inputs [37].
Neuroimmune interaction resulting from the action of chemical signals produced by
inflammatory cells on nerve fibers may contribute to peripheral and central sensitization.
Transcription-dependent central sensitization has been studied in the context of peripheral
inflammation where changes in brain derived neurotrophic factor (BDNF), substance P,
neurokinin 1 (NK1), dynorphin and cyclooxygenase 2 (Cox 2) are well described [38-40].
Neuron-glial interactions may also contribute to nociceptive processes [41]. The
macrophage-like glial cells, quiescent in the normal spinal cord, are rapidly activated after
nerve injury. These cells are a likely source of cytokines and chemokines that then act on
neurons and their supporting glia to alter patterns of gene transcription.

Ectopic excitability Increased excitability of injured and neighboring uninjured sensory

neurons can generate pacemaker-like ectopic action potential discharges, resulting in
sensory inflow independent of a peripheral stimulus [42,43]. These changes may manifest
at the site of the injury, at a neuroma, or in the dorsal root ganglion [44]. These ectopic
signals arise due to multiple factors including upregulation of voltage gated sodium
channels, channel subunits, or signal receptors in myelinated neurons; or downregulation
of potassium channels [45,46].
Structural reorganization/phenotypic switch Nerve injury may result in an altered
profile of sensory neurons. The central terminals of nociceptor sensory neurons terminate
in the most superficial laminae of the dorsal horn in the spinal cord. In contrast, low
threshold sensory fibers activated by touch, pressure, vibration, and normal ranges of
movement of joints terminate in the deep laminae of the dorsal horn.
Experiments in rodents have shown that physical rearrangement of this circuitry may occur
after peripheral nerve injury, with new growth of the central terminals of the low-threshold
afferents seen in the zone normally occupied exclusively by nociceptor terminals [47].
Additionally, after peripheral nerve injury, the neuromodulators brain-derived neurotrophic
factor (BDNF) and substance P, normally expressed only in C-fibers, may begin to be
expressed in large-diameter A fiber neurons [48,49].
Primary sensory degeneration Loss of neurons (normally a source of growth factors)
and the resulting imbalance of sensory inflow may contribute to the abnormal sensations
[12]. This paradoxical increase in pain perception with neurite dropout is not well
understood. Conceivably, this may be related to changes in neurotrophic factors,
compensatory local changes in the surrounding neurons or dorsal
root ganglion/dorsal horn of the spinal cord, changes in related glia, and/or changes in
cortical interpretation of afferent input.
Disinhibition A reduction in inhibition can have an effect similar to increased
excitability. Pharmacologically blocking GABA or glycine-mediated inhibition produces a
pattern of pain hypersensitivity similar to that of neuropathic pain, with prominent tactile
allodynia [50]. GABA blockade recruits previously absent ABeta fiber inputs to lamina II
cells, effectively uncovering a previously silent synaptic pathway [51].
Partial nerve injury also reduces inhibition in the superficial dorsal horn, with selective loss
of GABAergic inhibitory synaptic currents due to apoptosis in GABAergic inhibitory
interneurons [52]. One week after nerve injury that produces hypersensitivity to pain,
neurons begin to undergo apoptosis in the dorsal horn. The apoptosis may be due to
excessive glutamate release or failure of glutamate uptake, or result from cell deathinducing signals, such as release of tumor necrosis factor-alpha from activated microglia.
Clinical implication of mechanism of pain When pain symptoms fail to respond to
traditional treatment, conventional approaches may be supplemented by a mechanism-

based approach in efforts to individually tailor targeted therapy [53,54]. A mechanismbased approach accounts for the observation that patients with one disease (eg, diabetic
neuropathy) may have different symptoms due to different mechanisms [55]. Data
regarding the determination of the precise pain mechanism in a given patient, and the
effectiveness of therapy targeted to the mechanism, are preliminary, but current
knowledge provides a framework for future investigation
____________________-

Evaluation of chronic pain in adults

INTRODUCTION Chronic pain affects more than 100 million people in the United
States [1,2] and accounts for 20 percent of outpatient visits, 12 percent of all prescriptions,
and over 100 billion dollars in direct and indirect expenses [3]. Pain-related expenditures
(direct costs and lost wages) in the United States exceed those for cancer, heart disease,
and diabetes combined [4]. The use and misuse of opioids for management of chronic
pain is a major concern, with problems arising from their multiple adverse side effects
including drug dependency, from drug diversion, and from under-treatment of chronic pain
symptoms for fear of opioid abuse. Chronic pain is thus a major medical and social issue,
affecting the quality of life of individual patients, their friends and families, the work force,
and society in general.
A comprehensive pain evaluation is essential to developing an effective plan for treatment.
Although there are unique aspects to every individual's pain complaints, there are many
common elements to the pain evaluation, irrespective of the pain complaint. An
appropriate history and physical examination are vital to a proper evaluation. Laboratory
studies, imaging, and other diagnostic testing may be appropriate in selected situations.
The evaluation of patients complaining of persistent pain is discussed here. The definition,
classification, and pathogenesis of chronic pain, and overview of its treatment are
discussed separately. (See "Overview of the treatment of chronic non-cancer
pain" and "Definition and pathogenesis of chronic pain".)
COMMON CAUSES OF CHRONIC PAIN Although pain is one of the most common
presenting symptoms to the primary care clinician, only a percentage of patients ultimately
develop a chronic pain syndrome. In a study based on a survey of representative
population in the United States from 1999 to 2002 (the National Health and Nutrition
Examination Survey, NHANES), chronic pain (defined as >three months of pain) was
reported as follows: back pain 10.1 percent, leg/foot pain 7.1 percent, arm/hand pain 4.1
percent, headache 3.5 percent, chronic regional pain 11.1 percent, widespread pain 3.6
percent; the majority of patients who reported chronic pain reported more than one type of
pain [5].

Chronic pain can be considered to be in one of four categories. Identifying which of these
categories the patient falls into is helpful in designing an appropriate treatment plan,
although multifactorial causes of chronic pain are not uncommon. These pain categories
can be considered to be [6]:
Neuropathic pain (either peripheral, including post-herpetic neuralgia, diabetic
neuropathy; or central, including post-stroke pain or multiple sclerosis)
Musculoskeletal pain (eg, back pain, myofascial pain syndrome, ankle pain)
Inflammatory pain (eg, inflammatory arthropathies, infection)
Mechanical/compressive pain (eg, renal calculi, visceral pain from expanding tumor
masses)
Note that these categories are not entirely mutually exclusive, since back pain might be
considered both musculoskeletal and mechanical/compressive if it results from nerve root
compression.
HISTORY A thorough history is crucial to the evaluation of the patient with chronic pain.
Pain assessment should be a routine part of any medical encounter and has been referred
to as the fifth vital sign in both hospital and ambulatory settings [7]. Familiarity with the
patient and input from families, friends, and support systems will aid in assessing the true
impact of pain on the patient's life and in determining reasonable goals. It is also helpful to
inquire about the patient's perception of why they have persistent pain.
Pain characteristics The history should review all components of a usual medical
history, in addition to specific pain-related items. The patient should be asked a detailed
history related to the circumstances surrounding the onset of pain (if known) and potential
mechanisms of injury. Open-ended questions, at least initially, should be used to ascertain
the nature of the pain. Descriptors (such as sharp, dull, squeezing, throbbing, colicky) can
be offered if the patient cannot fully describe their symptoms.
Important symptom-related factors to be determined are:
Pain location
Radiation
Intensity
Characteristics/quality
Temporal aspects: duration, onset, changes since onset
Constancy or intermittency
Characteristics of any breakthrough pain
Exacerbating/triggering factors
Palliative/relieving factors

Associated symptoms Other symptoms that may be associated with the patient's pain
should be questioned:
Restriction of range of motion, stiffness, or swelling
Muscle aches, cramps, or spasms
Color or temperature changes
Changes in sweating
Changes in skin, hair, or nail growth
Changes in muscle strength
Changes in sensation, either positive (dysesthesias/itching) or negative (numbness)
Pain impact The patient should be questioned about the impact of pain on function
(social and physical) and overall quality of life. Specific questions to ask include:
Social and recreational functioning: How often do you participate in pleasurable
activities, such as hobbies, going out to movies or concerts, socializing with friends,
and travel? Over the past week, how often has pain interfered with these activities?
Mood, affect, and anxiety: Has pain interfered with your energy, mood, or
personality? Are you readily tearful?
Relationships: Has pain affected relationships with
family members/significantothers/friends/colleagues?
Occupation: Has the pain required that you modify your work
responsibilities and/or hours? When was the last time you worked, and (if applicable)
why have you stopped working?
Sleep: Does pain interfere with your sleep? How often over the past week?
Exercise: How often do you do some sort of exercise? Over the past week, how
often has pain interfered with your ability to exercise?
Activities of daily living The impact of pain on basic activities of daily living (ADLs)
should be assessed, addressing the patient's ability to bathe, dress, go to the toilet, and
feed without help. Questions also should be asked about activities required to live
independently (instrumental activities of daily living or IADLs), including the ability to shop,
use transportation, prepare meals, do housework, manage finances and medications.
Specific questions which, in conjunction with a physical examination, may help to
document a patient's function include:
Is the patient able to perform activities of daily living?
Can they brush their teeth, comb their hair, or bathe?
Can they manage using the toilet and cleaning without assistance?
Can they feed themselves?
Is the patient ambulatory?
Do they need an assist-device (eg, cane, brace, walker, crutch)?

Has their ambulation changed since the pain started?

How far can the patient ambulate?
How fast can they walk (eg, how long does it take the patient to get from the
parking lot to your office, compared to your own time?)
Is the patient able to dress independently?
Able to put his/her own shoes and socks on?
Can the patient put a shirt on himself?
If the patient wears a bra, is she able to put it on by herself?
Is the patient able to manage household chores, including shopping, cooking, bill
paying?
Is the patient able to drive a car?
Can the patient get in and out of a car with relative ease?
Is the patient able to get up and down from sitting on a chair or toilet?
Pain intensity scales Pain intensity can only be determined by the patient's report.
Measures of pain intensity are not meant to compare one person's pain with another's.
Pain scales are reliable only to compare the intensity of one patient's pain at different
times, thus allowing clinicians and patients to judge whether pain intensity is increasing or
decreasing with time and treatment.
A number of different measurements for pain intensity have been developed, and no scale
is clearly better than another. Most scales in common use are unidimensional. Some
patients have greater ease with a verbal scale, others with a numerical rating scale (NRS)
or a visual analog scale (VAS) (figure 1). The NRS-11 (a number scale from 0 to 10) is
perhaps the most commonly used pain intensity rating tool. A verbal scale offers
descriptors, such as "no pain, mild pain, moderate pain, severe pain, unbearable pain" that
can be graded on each visit. Pain maps (body maps) can be useful for patients who have
difficulty with verbal expression. A front and rear view of the body is presented on paper,
and the patient is asked to pencil in the location of the pain. Asking the patient to map out
the distribution of pain on their own body also may be helpful.
A consistent measure of pain for an individual patient should be used across time. Patients
should be asked to rate both pain present at the time of visit, and pain experienced over
the past week.
Multidimensional instruments provide more information than unidimensional scales, but
take longer to administer. Since chronic pain affects a persons whole life, many experts
feel that it is essential to use multidimensional instruments for appropriate assessment [6].
The Brief Pain Inventory (BPI) is a short, user-friendly self-administered, practical
questionnaire that is in many languages and has been validated for cancer pain and
noncancer pain [8,9]. The BPI assesses pain location, intensity, and pattern as well
as patient beliefs and the impact of pain on the patients quality of life.

The revised version of the short form of the McGill Pain Questionnaire (SF-MPQ-2)
includes a selection of descriptive words to characterize qualities of pain, a pain
intensity scale, a questionnaire on the use of analgesic medications and prior pain
experience, and a human figure drawing [10]. Specific words selected to characterize
the pain quality may suggest a particular pathophysiology (eg, burning, dysesthetic,
or electric-shock-like pain may imply neuropathic pain).
Specific instruments have been developed for the evaluation of neuropathic pain, and
include the following:
The Neuropathic Pain Scale, administered verbally, with established predictive
validity that assesses different qualities of neuropathic pain and can be used to follow
treatment response [11-13].
The S-LANSS score (8-Bennett 05) - A self-support version of the Leeds
Assessment of Neuropathic Symptoms and Signs (LANSS), consisting of five selfreported items and two patient-assessed sensory testing items (table 1) [14].
The DN4 - A clinician-administered tool with 10 items based on history and physical
examination [15], has a cut-off value of 4/10 for the diagnosis of neuropathic pain
(positive item score = 1, negative items score = 0). The DN4 has a positive predictive
value of 86 percent, sensitivity of 82.9 percent, and a specificity of 89.9 percent
(figure 2).
Previous evaluation and/or treatment Prior evaluation and treatment for pain should
be explored. Attempts should be made, with patient permission, to obtain all records from
clinician offices, hospitals, imaging centers/laboratories, and pharmacies.
Questions to be asked include:
Have you experienced other painful illnesses?
What health care professionals have treated you in the past or are currently treating
you? (Include clinician addresses and phone numbers.)
What tests/imaging studies or other diagnostic studies have you had?
What medications have been tried? How have you responded
to medications/treatments in the past? This information should include dosing, length
of medication trials, frequency of use of "prn" medications, perceived effectiveness,
and perceived adverse or other side effects.
Have you seen a complementary or alternative medical practitioner for your
symptoms? If so, was their treatment helpful?
Do you use herbal medications, vitamins or other supplements? Do you follow a
special diet?
Patient perceptions and psychological factors The patient's personal and family
history should be explored as part of a behavioral assessment. It is important to inquire
about a patient's support system.

Patients should be asked about possible maladaptive behavioral patterns that may
influence the course of pain rehabilitation. Of particular concern is history related to
underlying psychological disorders (eg, depression, anxiety) or a history of substance
abuse, including prescription drugs.
A patient's specific beliefs about their pain and their prior healthcare experiences should
be understood [16]. It is crucial to determine the patient's expectations for treatment and to
educate and counsel patients with respect to how realistic these expectations and goals
are. A significant mismatch or gap between expectations and reality will lead inevitably to
frustration for both patient and clinician.
Questions to be asked include:
What is the patient's perception of why they have persistent pain?
Does the patient believe an adequate diagnostic work-up has been done?
Does the patient have expectations for specific types of treatments?
What are the patient's expectations or goals of treatment (eg, extent of pain relief
and functional improvement)?
How involved does the patient expect to be in their treatment?
PHYSICAL EXAMINATION A complete physical examination, including a detailed
neurologic assessment, should be performed, regardless of the patient's area of complaint.
A baseline evaluation will allow ongoing assessment of a patient's progress in terms of
functional capacity, range of motion, endurance, strength, and other pain-related clinical
manifestations.
Relevant components of the physical examination for specific types of chronic pain are
discussed separately. (See "Evaluation of low back pain in adults" and "Evaluation of
chronic pelvic pain in women" and "Outpatient evaluation of the adult with chest
pain" and "Clinical manifestations and diagnosis of fibromyalgia in adults" and "Evaluation
of the adult with polyarticular pain".)
Important information can be obtained by observing the patient as they walk into the
examination room, and by observing pain behaviors throughout the examination. The
patient's general appearance, dress, and hygiene should be noted.
Compensatory movements, or splinting, may serve to protect a painful region of the body,
and consistency of such activities should be observed. Suggestions of pain embellishment
should be noted, but do not necessarily indicate malingering since patients with
longstanding chronic pain may enhance their presenting symptoms to assure themselves
that the clinician will accept and explore their complaints.
DIAGNOSTIC TESTING Pain is a subjective complaint and cannot be assessed with
laboratory studies. However, appropriate laboratory, imaging, and other testing can be

helpful to evaluate or follow certain painful conditions. It should be borne in mind, however,
that finding an abnormality in a diagnostic test does not confirm that this is the source of
the patients pain syndrome.
Blood tests Routine blood studies are not indicated, but directed testing should be
ordered when specific causes of pain (ie, rheumatologic, infectious, or oncologic) are
suggested by the patient's history or physical examination. Serologic markers of
inflammation such as erythrocyte sedimentation rate and C-reactive protein should be
normal in degenerative or neuropathic causes of pain but may be elevated in patients with
polymyalgia rheumatica, rheumatoid arthritis, or infectious processes (eg, septic discitis).
(See "Clinical manifestations and diagnosis of polymyalgia rheumatica".)
Imaging It is likely that patients with chronic pain complaints will already have had
diagnostic imaging studies from previous evaluations, and these should be obtained and
reviewed if possible, to avoid unnecessary radiation exposure and expense.
Indications for imaging and other studies will vary depending on the location of the
patient's pain and are discussed in multiple other topics in UpToDate. (See "Evaluation of
low back pain in adults" and "Evaluation of chronic pelvic pain in women" and "Outpatient
evaluation of the adult with chest pain" and "Clinical evaluation of musculoskeletal chest
pain" and "Evaluation of the patient with neck pain and cervical spine
disorders" and "Overview of cancer pain syndromes" and "Overview of craniofacial
pain" and "Evaluation of the adult with polyarticular pain".)
Other testing Neurophysiologic testing, principally nerve conduction studies (NCV) and
electromyography (EMG), are frequently employed in suspected disorders of the
peripheral nervous system. The usual techniques, with surface electrodes for nerve
stimulation, measure activity of the largest and fastest conducting sensory and motor
myelinated nerve fibers. (See "Overview of electromyography".)
Unfortunately, NCV and EMG studies may be normal in patients with polyneuropathies or
focal nerve lesions with only small-fiber involvement. Additionally, pain specialists may
perform interventional testing of nerves or joints via a double-comparative local anesthetic
blockade (eg, with one block using a longer acting anesthetic).
REFERRAL TO A PAIN SPECIALIST The Institute of Medicine in the United States,
recognizing the enormous population burden of chronic pain, formed a committee to
explore related issues and published a report in 2011 [17]. This report identified limitations
in the training of generalist clinicians in the management of chronic pain, noting that it is
not realistic or desirable that pain management be delegated exclusively to pain
specialists. To support generalist clinicians in the management of their patients with
chronic pain, issues related to training, education, and reimbursement need to be
addressed.

While many patients with chronic pain can be managed without specialty referral, patients
may require referral to a pain specialist for one of several reasons:
Symptoms that are debilitating
Symptoms located at multiple sites
Symptoms that do not respond to initial therapies
Escalating need for pain medication
When to refer to a pain specialist remains a controversial question; referral should
certainly occur by the time significant disability or loss of functioning are observed or when
pain behaviors have coalesced or maladaptive coping strategies have begun to emerge.
Most pain specialists feel that referrals are frequently made too late in the course of pain,
when patients are beyond "the golden hour." This is especially true of neuropathic forms of
pain and cancer pain.
SPECIAL CONSIDERATIONS IN SPECIFIC POPULATIONS
Psychiatric comorbidity A significant portion of patients presenting with chronic pain
also have histories of primary psychiatric comorbidity [18]. The inclusion of Axis I and/or II
diagnoses in the patient's history should never provide the grounds to dismiss the patient's
complaints of pain.
Nociceptive pathways are modulated by psychological processes, which probably play an
important role in amplifying pain symptomatology [19]. Depression, anxiety, posttraumatic
stress disorder, substance abuse, and other psychiatric disorders can present formidable
obstacles to diagnosing and treating many pain syndromes. In one prospective study,
patients with a mental health diagnosis were twice as likely to be prescribed an opioid
medication three years later than those without a psychiatric diagnosis [20].
Patients with longstanding or complex pain problems should be treated with a
multidisciplinary approach that includes an evaluation and close collaboration by a mental
health professional who can diagnose and treat the psychologic aspects of the
dysfunction.
It is important to distinguish patients with underlying psychiatric illness from those whose
psychological symptoms (anxiety, depression, or other expressions of psychopathology)
arise secondary to their pain. Chronic pain can take an emotional toll, affecting
relationships with loved ones, friends, and potentially employers. Besides living with pain,
the patient may feel angry, isolated, helpless, and fearful that he or she has lost the ability
to engage in productive employment, or be a good spouse, parent, or friend. Somatoform
pain disorder, in which pain is not fully explained by a general medical condition, is
discussed separately. (See "Somatization: Epidemiology, pathogenesis, clinical features,
medical evaluation, and diagnosis", section on 'Somatoform disorders'.)

Depression and anxiety, two of the most common psychological correlates of chronic pain,
complicate the patient's conditions [21]. Sleep disturbance, loss of appetite, lack of energy,
and diminished physical activity contribute to an increasingly debilitated state and amplify
the patient's pain symptoms. Patients commonly describe a lack of pleasure and an
absence of control in their lives.
A number of instruments or psychological tests are widely employed to screen the
psychological profiles of chronic pain patients. Two that are in common use are the Beck
Depression Inventory and the Minnesota Multiphasic Personality Inventory II (MMPI-2).
The former is a brief, 21-item, self-reporting questionnaire that assesses the degree to
which depressive symptomatology is present. The latter is an
extensive true/false questionnaire consisting of more than 500 items factored across 10
clinical scales, as well as a variety of validity, secondary, and experimental scales. The
MMPI-2 has been used extensively to verify clinical impressions about the psychological
aspects of a patient's chronic pain and to predict responses to medical and surgical pain
treatments [22-24].
Older adults Successful pain management in the older adult, as with younger
individuals, is predicated on a comprehensive pain assessment. Specific goals include
determining the type and cause of pain; identifying exacerbating co-morbidities; reviewing
beliefs, attitudes, and expectations regarding pain; and gathering information that would
assist and impact an individualized treatment plan [25].
Self-report of pain is the most reliable source for the cognitively intact and communicative
older adult [26]. However, older patients may have more difficulty in communicating their
pain, and are often undertreated for pain [27]. Deficits in vision, hearing and cognition are
common in this population and need to be identified prior to beginning the interview.
Adjustments to accommodate for deficits that may compromise the assessment need to be
considered, especially when selecting appropriate pain assessment instruments. It also
may be beneficial to query other family members or caregivers for corroboration and
additional perspective on medical history, predominant mood and affect, and physical and
social functioning [28].
For a variety of reasons, older adults may be more hesitant than younger individuals to
report pain. Some barriers to discussing pain include: perception that pain simply is a
concomitant of aging; reluctance to bother their clinician with complaints of pain; not
wanting to detract the clinicians attention away from other medical complaints. Older
adults also may use different descriptive terms for their pain (aching, soreness, hurting,
discomfort), including some that are not included in commonly used pain instruments
[20,27].
Medication history A careful medication history must include all current and past
medications, doses, side effects, and response [28]. Many older individuals living in the
community cannot accurately provide this information. It is helpful to ask that they bring in

all current medications, as well as to obtain corroborative information from other treating
clinicians and from relatives and to obtain the name and phone number of the patient's
current pharmacy [28]. (See "Drug prescribing for older adults".)
Patients should be specifically questioned about use of herbal and dietary supplements, as
well as over the counter medications, in addition to prescription medications. Data from
2002 indicate that approximately one-quarter of older women in the US regularly use an
herbal or dietary supplement [29]. Additionally, patients should be asked about alcohol
use, with specific inquiry regarding type, frequency and amount. Tobacco products and
illicit drug use are important elements of inquiry as well.
Functional assessment Cognition is grossly assessed during the process of the health
interview. More detailed assessment may be indicated for patients who seem to have
cognitive impairment. (See "Evaluation of cognitive impairment and dementia".)
Psychosocial assessment Mood, social support systems, recreational involvement,
and financial resources are important to the psychosocial assessment. These factors
influence how the patient experiences the pain and how the patients may respond to
various treatments [28].
Beliefs and attitudes about pain The context in which older adults perceive pain is
relevant to the overall assessment. Older adults are more likely to view severe discomfort
as a sign of serious or life-threatening illness (eg, recurrence of cancer). Pain can signify
loss of independence, debilitating illness, or may be regarded as a natural consequence of
the aging process and therefore be underreported.
Identifying coping skills among the elderly is important so that the clinician can encourage
the use of previously successful skills or modify treatment interventions to promote
effective coping skills. The most consistent findings in studies is that older persons use
prayer and hope as pain coping mechanisms to a greater extent than do younger patients
[30,31].
Long-term care facilities Several studies have identified problems with pain
assessment in the nursing home setting [21,32,33]. In one study involving focus groups in
12 nursing homes, behavioral changes and observable physical changes were used as
cues for the possible presence of pain, rather than formal assessment [21]. Pain
assessment was recognized as more problematic for residents whose relationships with
nursing staff were more limited and who were considered behaviorally "difficult."
Two resources to facilitate implementing an institutional plan for pain assessment are the
American Geriatric Society Panel on Persistent Pain in Older Adults [26] and the American
Medical Directors Association Chronic Pain Management in the Long Term Care Setting
guidelines [33].

Nonverbal or cognitively impaired adults Five key principles to guide pain

assessment in nonverbal populations have been identified by the American Society for
Pain Management Nursing (ASPMN) [34]. These are:
Obtain a self-report of pain, if at all possible
Investigate for possible pathologies that could produce pain
Observe for behaviors that may indicate pain
Solicit a surrogate report from an observer or caregiver
Consider the use of an analgesic trial to evaluate whether pain management results
in a reduction in the behavioral indicators thought to be related to pain
A variety of behavioral tools have been developed for pain assessment in nonverbal older
adults, but none has been found to have sufficient reliability and validity to support broad
adoption in clinical practice [34-40]. These tools include:
Checklist of Nonverbal Pain Indicators (CNPI) for acute care [27,41].
The Doloplus 2 for nonverbal older adults who speak French, Dutch, and Norwegian
[42].
The Pain Assessment Checklist for Seniors with Severe Dementia (PACSLAC) [43],
which addresses all six pain behavioral categories included in the AGS Guidelines
[44].
The Pain Assessment in Advanced Dementia (PAINAD) Scale for nonverbal older
adults with advanced dementia [45].
The Behavioral Pain Scale (BPS) for critically ill sedated adult patients undergoing
mechanical ventilation [46].
The Critical Care Pain Observation Tool (CPOT) also for critically ill patients unable
to communicate verbally [47].