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Assessment of Neuropathic Pain in Primary Care

Maija L. Haanpää, MD, PhD,a,b,c Misha-Miroslav Backonja, MD, PhD,d Michael I. Bennett, MB, ChB,e
Didier Bouhassira, MD, PhD,f Giorgio Cruccu, MD, PhD,c,g Per T. Hansson, MD, DMSc, DDS,c,h
Troels Staehelin Jensen, MD, PhD,c,i Timo Kauppila, MD, PhD,j,k Andrew S. C. Rice, MB, BS, MD, FRCA, FFPMRCA,l
Blair H. Smith, MB, ChD, MD,m Rolf-Detlef Treede, Dr.med.,n Ralf Baron, Dr.med.o
a
Department of Neurosurgery, Helsinki University Central Hospital, Helsinki, Finland; bRehabilitation ORTON, Helsinki, Finland;
c
European Federation of Neurological Societies (EFNS) Panel on Neuropathic Pain, Vienna, Austria; dDepartment of Neurology,
University of Wisconsin, Madison, Wisconsin, USA; eInstitute of Health Research, Lancaster University, Lancaster University,
Lancaster, United Kingdom; fCentre d’Evaluation et de Traitement de la Douleur, Hôpital Ambroise Paré 9, Boulogne-Billancourt,
France; gDepartment of Neurological Sciences, La Sapienza University, Rome, Italy; hPain Center, Department of Neurosurgery,
Section of Clinical Pain Research, Karolinska University Hospital and Institute, Stockholm, Sweden; iDanish Pain Research Center and
Department of Neurology, Aarhus University Hospital, Aarhus, Denmark; jNetwork of Academic Health Centers, Department of
General Practice and Primary Health Care, Institute of Clinical Medicine, University of Helsinki, Helsinki, Finland; kKorso Health
Care Center, Vantaa, Finland; lDepartment of Anesthetics, Pain Medicine, and Intensive Care, Imperial College London, Chelsea &
Westminster Hospital Campus, London, England, United Kingdom; mUniversity of Aberdeen, Foresterhill Health Center, Aberdeen,
Scotland, United Kingdom; nDepartment of Neurophysiology, Center for Biomedicine and Medical Technology–Mannheim, Heidelberg
University, Mannheim, Germany; and oDivision of Neurological Pain Research and Therapy, Department of Neurology,
Universitatsklinikum Schleswig-Holstein, Kiel, Germany.

ABSTRACT

Management of patients presenting with chronic pain is a common problem in primary care. Essentially,
the classification of chronic pain falls into 3 broad categories: (1) pain owing to tissue disease or damage
(nociceptive pain), (2) pain caused by somatosensory system disease or damage (neuropathic pain), and (3)
pain without a known somatic background. Key challenges in developing a targeted holistic approach to
treatment include appropriate diagnosis of the cause or causes of pain; identifying the type of pain and
assessing the relative importance of its various components; and determining appropriate treatment. In
clinical examination, sensory abnormalities are the crucial findings leading to a diagnosis of neuropathic
pain, for which pharmacotherapy with antidepressants and anticonvulsants represents the cornerstone of
medical treatment. Chronic neuropathic pain is underrecognized and undertreated, yet primary care
physicians are uniquely placed on the frontlines of patient management, where they can play a pivotal role
in treatment and prevention through diagnosis, therapy, follow-up, and referral. This review provides
guidance in understanding and identifying the neuropathic contribution to pain presenting in primary care;
assessing its severity through patient history, physical examination, and appropriate diagnostic tests; and
establishing a rational treatment plan.
© 2009 Elsevier Inc. All rights reserved. • The American Journal of Medicine (2009) 122, S13–S21

KEYWORDS: Allodynia; Assessment; Neurological testing; Neuropathic pain; Pain measurement; Somatosensory testing

Pain is the reason for 40% of patient visits to a primary care

Statement of author disclosure: Please see the Author Disclosures
section at the end of this article.
This work was supported in part by travel grants from NeuPSIG, the
Special Interest Group on Neuropathic Pain of the International Associa-
tion for the Study of Pain (IASP).
Requests for reprints should be addressed to Maija L. Haanpää, MD,
PhD, Department of Neurosurgery, Helsinki University Central Hospital,
PO Box 266, 00029 HUS, Helsinki, Finland.
E-mail address: maija.haanpaa@hus.fi
physicians each year, and approximately 20% of these pa-
tients have experienced their pain for ⬎6 months.1 Because
of its complexity, the presentation of chronic pain poses a
diagnostic and management challenge to the physician.
Chronic pain is both the source of severe patient suffering
and a major cause of work abseenteism2; obtaining the
correct diagnosis through identifying the type and origin of
pain and instituting appropriate early management thus im-

0002-9343/$ -see front matter © 2009 Elsevier Inc. All rights reserved.
doi:10.1016/j.amjmed.2009.04.006
S14
Table 1 Conditions That Carry a Risk for Neuropathic Pain*
Condition
Peripheral neuropathic pain
Radiculopathy (lumbosacral, thoracic, or cervical)
Polyneuropathy (e.g., diabetic, alcoholic, postchemotherapy, HIV disease)
Postherpetic neuralgia†
Postsurgical neuralgia (e.g., postmastectomy pain)
Nerve trauma
Entrapment neuropathy
Trigeminal neuralgia
Central neuropathic pain
Stroke
Multiple sclerosis
Spinal cord injury
Phantom limb pain
HIV ⫽ human immunodeficiency virus.
*Some fit the definition of a neuropathic pain condition.
†Defined as pain continuing after the healing of a rash.
Adapted from Diabet Med,9 Diabetes Care,10 Curr Med Res Opin,11 Arch Intern Med,12 Pain13,15,16 Neurology,14 Eur J Pain,17 and Spinal Cord.18
proves health outcomes and yields significant cost benefits
to society. Management approaches consist of empowering
patients through counseling, education, self-management
strategies, and psychosocial support, as well as palliative or
curative medical treatment.
Classification of chronic pain conditions falls into 3
broad categories: (1) nociceptive pain, which occurs as a
result of tissue disease or damage but in the presence of a
functionally intact sensory nervous system (e.g., osteoar-
thritis); (2) neuropathic pain, which arises when the nervous
system itself is diseased or damaged (e.g., postherpetic
neuralgia); (3) and chronic pain that occurs without known
somatic background. Diagnosis is challenging because these
different types of pain may occur singly or in combination
in the same pain patient, and even at the same body site
(e.g., radiating from or distributed into 1 or more lumbosa-
cral roots).
GLOBAL VARIATION IN NEUROPATHIC PAIN
The main causes of neuropathic pain vary geographically. In
developing countries, infectious diseases such as human
immunodeficiency virus (HIV)3,4 and leprosy,5 trauma (e.g.,
due to war wounds and amputations),6 and radiculopathies
related to spinal column diseases7 are among the most
common causes of neuropathic pain. Sensory neuropathy is
the most frequent neurologic complication of HIV infection
or its treatment with antiretroviral agents and affects up to
40% of patients with advanced HIV disease.8 Neurotoxic
antiviral agents such as stavudine and didanosine are often
used in resource-poor settings.4 In developed countries, the
most frequent causes of neuropathic pain are diabetic poly-
neuropathy9,10 and radiculopathies with neuropathic pain
components.11 Common disorders that carry a risk of de-
veloping neuropathic pain in patients in developed countries
The American Journal of Medicine, Vol 122, No 10A, October 2009
Epidemiology
37% in patients with prolonged low back pain11
16% in patients with diabetes mellitus9
26% in patients with type 2 diabetes10
8% incidence in patients with herpes zoster12
Not known (⬃30%-40% after breast cancer surgery)13
5% after verified trigeminal nerve injury14
Not known
Incidence of 27/100,000 person-yr15
8% in patients with stroke16
28% in patients with multiple sclerosis17
67% in patients with spinal cord injury18
Incidence of 1/100,000 person-yr15
are listed in Table 1.9-18 Herpes zoster12 and peripheral
nerve traumas13-15 are the most frequent causes of periph-
eral neuropathic pain, whereas stroke,16 multiple sclero-
sis,17 and spinal cord injuries18 are the major causes of
central neuropathic pain. The wide range of potential causes
of neuropathic pain clearly indicates that diagnostic proce-
dures to detect painful neuropathy must always accompany
the search for underlying disease.
Two population-based studies in which screening tools
were used to identify neuropathic pain revealed that it is
associated with an excessive psychosocial burden compared
with nociceptive pain, and that it is able to induce more
intense psychological comorbidity than other types of
chronic pain.11,19 Another investigation also reported that
neuropathic pain is more severe than other pain types.20 In
contrast, however, a study of subjects in pain management
clinics reported that patients with postherpetic pain and
patients with nonneuropathic low back pain were similar in
their reports of pain, dysfunctional cognition, mood, and
physical function, perhaps reflecting the selected nature of
the patient cohort.21
Early detection of psychosocial problems is of special
importance in the management of chronic pain; manage-
ment of stress due to psychosocial causes should be an
integral part of the overall pain treatment plan. Recognition
of the neuropathic origins of pain may be helpful for ex-
plaining the mechanisms of specific symptoms and making
an estimation of the prognosis. Appropriate information
may help patients cope with everyday problems associated
with their disease.22 In some cases, early recognition of the
underlying neuropathic pathophysiology may allow physi-
cians to move beyond pain management and achieve a cure.
For example, in carpal tunnel syndrome, adequate surgical
treatment may relieve pain.23 Furthermore, because phar-
Haanpää et al Assessment of Neuropathic Pain in Primary Care
macotherapy is selected on the basis of pain type, determi-
nation of pain as nociceptive or neuropathic is a prerequisite
to adopting the correct approach.
Neuropathic pain is probably underrecognized, and
therefore undertreated, in primary care.1 As a result, al-
though many medications with evidence of efficacy are
available for neuropathic pain,24-26 they are probably un-
derprescribed.27 At the same time, conventional analgesics,
such as nonsteroidal anti-inflammatory drugs (NSAIDs), are
prescribed frequently for patients with neuropathic pain
despite potential risks and limited efficacy.28 Inappropriate
or delayed treatment is a serious concern because it may
worsen the patient’s condition.
WHAT IS NEUROPATHIC PAIN?
The International Association for the Study of Pain (IASP)
defines neuropathic pain as “pain arising as a direct conse-
quence of a lesion or disease affecting the somatosensory
system.”29 It is common in clinical practice to classify
neuropathic pain according to the underlying etiology of the
disorder and the anatomical location of the specific lesion.30
If possible, neuropathic pain should also be qualified as
being of peripheral or central origin in terms of the location
of the lesion or disease process. There are sufficient simi-
larities in the mechanisms and responses to treatment of
different subtypes of peripheral neuropathic pain and central
neuropathic pain to make categorizing them into these
broader clinical entities yield useful information. The dif-
ferentiation is important because lesions or diseases of the
central and peripheral nervous systems are distinct in terms
of underlying pathophysiology, clinical manifestations, and
treatment requirements.
The characteristic symptoms of neuropathic pain make it
distinct from other chronic pain syndromes in which the
nervous system remains unaltered.31 The inciting injury
may be mild or severe, focal or diffuse, and may involve a
single or multiple distinct processes (e.g., mechanical, in-
flammatory, metabolic, or vascular) at any level of the
somatosensory system. Recent research into the mecha-
nisms of neuropathic pain has clearly revealed that the
physiologic changes produced in the peripheral and central
nervous systems are dramatic, although they remain poorly
understood with regard to their relation to the patient’s
experience of pain.
As mentioned previously, an important aim of clinical
examination and recording patient history is correctly cate-
gorizing the type of pain. In addition to identifying clear
nociceptive or neuropathic types, other chronic pain disor-
ders should be ruled out. For example, both nociceptive and
neuropathic processes may contribute to an overall clinical
picture of mixed pain, as in chronic low back pain with
pathology of the spine and nerve root.11,32 In these situa-
tions lack of efficacy of the effect of drugs aimed at noci-
ceptive pain may be an important hint at the presence of a
neuropathic pain component. In contrast, somatoform pain
disorder (with positive identification criteria according to
S15
the International Classification of Diseases, 10th Revision
[ICD-10]) and pain sine materia (diagnosed by exclusion)
are devoid of any evidence of nociceptive or neuropathic
processes.
HOW COMMON IS NEUROPATHIC PAIN?
Chronic neuropathic pain is a common presentation in clin-
ical practice, greatly impairs the quality of life of patients,
and poses a major economic burden to society. Although
epidemiologic data are available for many specific neuro-
pathic diagnoses (Table 1), there are relatively few data on
the total prevalence of neuropathic pain in the general pop-
ulation. A population-based survey of neuropathic pain
characteristics in 6,000 patients treated in family practices
in the United Kingdom reported that the prevalence of pain
of predominantly neuropathic origin was 8%, and patients
with neuropathic pain reported more intense and long-last-
ing pain and more greatly impaired quality of life compared
with respondents with other types of chronic pain.19,33 Sim-
ilarly, a large population-based study in France found that
6.9% of the subjects reported chronic pain with neuropathic
characteristics, with greater severity of symptoms compared
with other chronic pain types.20 According to a German
population-based study of patients with prolonged low back
pain, pain was predominantly neuropathic in 37%. Depres-
sion, anxiety, and sleep disorders were significantly more
prevalent in the patients with neuropathic pain compared
with those without neuropathic pain.11 A primary care–
based study from the United Kingdom reported a 26%
prevalence of chronic painful diabetic peripheral neuropa-
thy in patients with type 2 diabetes; the patients with neu-
ropathic pain also had a poorer quality of life compared with
the patients with nociceptive pain or no pain.10 Importantly,
even prediabetes (i.e., impaired glucose tolerance) can be
associated with neuropathic pain.34 Postsurgical pain also is
an important and underestimated iatrogenic cause of neuro-
pathic pain in primary care.35
WHY IS IT IMPORTANT TO DETECT
NEUROPATHIC PAIN IN PRIMARY CARE?
As mentioned above, the differential diagnosis of neuro-
pathic pain type is crucial, because it requires a different
therapeutic approach than nociceptive pain. Primary care
physicians hold a key diagnostic position because they
guide the early management of pain and have a pivotal role
in triaging patients for specific treatment approaches.36 A
diagnosis of neuropathic pain should be followed by a
targeted therapeutic strategy, including specific curative
treatments (when possible) and symptomatic pharmacother-
apy. Standard treatments such as NSAIDs and acetamino-
phen have no proven efficacy in neuropathic pain, whereas
other drug classes, such as anticonvulsants and antidepres-
sants, are more likely be effective in neuropathic than in
nociceptive pain. Thus, in the setting of severe pain, the
earlier an appropriate management plan is implemented, the
S16 The American Journal of Medicine, Vol 122, No 10A, October 2009

more likely it is that comorbidities, disability, and absen- Table 2 Common Features Suggestive of Neuropathic Pain
teeism or sick leave can be minimized.37
As in the case of any other chronic disease, management Term Definition
of neuropathic pain requires a sound relationship between Symptoms
patient and physician, with an emphasis on support, pa- Paresthesias Nonpainful positive sensations
tience, and targeted patient-centered strategies. Often it is (“antcrawling,” “tingling”)
not possible to cure the underlying disease or lesion com- Burning pain Frequent quality of spontaneous
pletely, or to reverse the resultant neurologic changes. pain sensations
Therefore, this type of pain is usually persistent. Secondary Shooting pain Spontaneous or evoked intense
care specialists will make important contributions to the pain sensation of several
seconds’ duration
treatment of patients, but they cannot always provide the
Signs
long-term relationship and consistent care that is possible in Hypoesthesia Impaired sensitivity to a stimulus
primary practice. Primary care physicians, therefore, have a Tactile hypoesthesia Impaired sensitivity to tactile
crucial role to play helping the patient with chronic pain stimuli
achieve optimal quality of life through minimizing discom- Cold hypoesthesia Impaired sensitivity to cold
fort and maximizing functional capacity. In the most chal- Hypoalgesia Impaired sensitivity to a normally
lenging cases, multidisciplinary approaches and pain reha- painful stimulus
bilitation therapy may be needed. Hyperalgesia Increased pain sensitivity (may
include a decrease in threshold
and an increase in
DIAGNOSING AND ASSESSING NEUROPATHIC suprathreshold response)
PAIN Punctate hyperalgesia Hyperalgesia to punctuate stimuli
such as a pinprick
Clinical History Static hyperalgesia Hyperalgesia to blunt pressure
Pain associated with nerve injury has several distinct clin- Heat hyperalgesia Hyperalgesia to heat stimuli
ical characteristics.38 If a mixed peripheral nerve with a Cold hyperalgesia Hyperalgesia to cold stimuli
Allodynia Pain due to a nonnociceptive
cutaneous branch or a central somatosensory pathway is
stimulus
involved, there is almost always an area of abnormal sen-
sation, and the patient’s maximum pain is usually coexistent Adapted from Handbook of Clinical Neurology.41,42
with or lies within an area of sensory deficit. This is a key
diagnostic feature of neuropathic pain.39 The sensory deficit
usually includes noxious and thermal perception, indicating separately. Depending on the lesion or the disease causing
damage to small-diameter afferent fibers. Besides these neg- the neuropathic pain, there may be other neurologic symp-
ative somatosensory signs (functional abnormalities), which toms and signs, such as motor weakness or symptoms re-
are usually troublesome but not painful, patients report lating to altered function of the autonomic nervous system.
various types of bizarre or unfamiliar feelings.40 These The location of the pain is best documented with a pain
positive symptoms include paresthesias and spontaneous drawing (Figure 1), created either by the patient or by the
(not stimulus-induced) ongoing pain and stabbing sensa- physician, to assess whether it is correlated with a particular
tions. Many patients also have evoked types of pain (stim- neuroanatomical distribution (e.g., a dermatome or periph-
ulus-induced pain, hypersensitivity). Most often, patients eral nerve territory). Any abnormal sensations may also be
report mechanical hypersensitivity, followed by hypersen- mapped on the same illustration.
sitivity to cold. A summary of terms commonly used to
describe these symptoms is presented in Table 2.41,42 Symptom-Based Screening Tools Used in
Neuropathic pain often has a burning, lancinating, or Clinical Practice
shooting quality with unusual tingling, crawling, or electri- No single symptom is diagnostic of neuropathic pain, but
cal sensations.43 Although none of these characteristics is combinations of certain symptoms, pain descriptors, and
universally present in, or absolutely diagnostic of, neuro- bedside findings increase the likelihood of a neuropathic
pathic pain, when they are present the diagnosis is highly pain condition.43,44 Several verbal screening tools based on
likely. The patient history should also clarify the quality, these signs and symptoms have been developed45-50; they
intensity, and time course of pain symptoms, as well as are simple and easy to use in clinical practice, and may alert
underlying diseases or comorbidities and previously at- the physician to the need for careful examination in search
tempted treatments. The intensity of pain can be assessed of neuropathic pain, but they are no substitute for sound
descriptively (e.g., “mild,” “moderate,” “severe,” “excruci- clinical judgment. The lack of suggested signs or descriptors
ating”), numerically (e.g., on a scale from 0 to 10), or using is no excuse for failing to examine the patient properly.
a visual analogue scale. If the pain has ⬎1 component (e.g., Each of these screening tools uses between 4 and 9 pain
continuous ongoing pain and superimposed lancinating descriptors, 3 of which (tingling, shooting, and burning pain
pain), the intensity of each component should be assessed sensations) are included in all of the questionnaires. The full
Haanpää et al Assessment of Neuropathic Pain in Primary Care S17

Figure 1 Pain drawing of a 47-year-old woman with intercostobrachial neuralgia on

the left side as a consequence of mastectomy following a malignant tumor.

neuropathic pain, abnormal sensory findings should be neu-

Table 3 Simple Tools for Assessment of Sensory Function
roanatomically logical, and compatible with a localized
Peripheral Nerve Clinical Testing lesion site.51 Neurologic examination is therefore aimed at
Fiber Type Sensation Instrument finding possible abnormalities relating to a lesion, allowing
A␤ Touch Fingers, piece of cotton its anatomic level (peripheral or central) to be determined.
wool, or soft brush Sensory testing is the most important part of this examina-
Vibration Tuning fork (128 Hz) tion; it is guided by the information obtained from the
A␦ Pinprick, sharp pain Wooden cocktail sticks patient history and pain drawing. Findings in the painful
Cold Cold object (20°C) area are compared with findings in the contralateral area in
C Warmth Warm object (40°C) the case of unilateral pain and in other sites on the proximal-
distal axis in the case of bilateral pain. Mapping of sensory
abnormalities is crucial, because sensory abnormalities
without neuroanatomical distribution may be present in pure
versions of the Leeds Assessment of Neuropathic Symp- nociceptive pain.52 Each sensory modality can be tested
toms and Signs (LANSS)45 and the Douleur Neuropathique separately using simple tools (Table 3). Sensory testing
en 4 questions (DN4)49 screening tools also include limited usually begins with simple touch, followed by pinprick
bedside sensory testing, but simpler patient-completed ver- testing. Testing of tactile sensation may be accomplished
sions have been developed from each of them. The pain- using light finger pressure when other tools are not avail-
DETECT tool was originally developed to detect neuro- able. If the findings of the tactile and pinprick modalities are
pathic disease components in patients with chronic low back normal, then thermal and vibratory senses should be tested
pain, but it is also useful for identifying other types of before declaring sensory function intact. If a thermoroller
neuropathic pain.11 The sensitivity (66% to 91%) and spec- (Somedic Sales AB, Horby, Sweden) is not available, a
ificity (74% to 94%) of these instruments fall within rea- metal object (e.g., the handle of a reflex hammer) cooled
sonable ranges.43 with tap water can be used as a substitute. The level of
response to each stimulus can be graded as normal, de-
Clinical Examination creased, or increased. The quality of response may differ
The first goal of examination of a patient with pain is to from normal; for example, cold may be sensed as burning
identify the underlying disease and pain type. In cases of (paradoxical heat sensation), or a normally painless stimu-
S18 The American Journal of Medicine, Vol 122, No 10A, October 2009
lus may provoke pain (allodynia).41 In the latter case, the
presence of dynamic mechanical allodynia is tested using a
light moving stimulus, while cold allodynia is tested with a
cold object. It should be noted that, as a rule, patients with
neuropathic pain frequently have deficits to one type of
stimulus while experiencing pain from others. This can be
confusing both to patients and to clinicians who are not
familiar with this presentation.
Additional Diagnostic Procedures
In clinically clear cases, such as postherpetic neuralgia, no
additional tests are needed, and pharmacotherapy can be
commenced according to evidence-based guidelines.24-26 In
Table 5 Additional Educational Resources
For Healthcare Professionals
● International Association for the Study of Pain (IASP)
(www.iasp-pain.org)
● IASP Special Interest Group on Neuropathic Pain (www.neupsig.org)
● British Pain Society—recommendations for clinical practice and pain
measurement tools are available in a variety of languages (www.
britishpainsociety.org)
● German Neuropathic Pain Research Network
(www.neuro.med.tu-muenchen.de/dfns)
● Oxford Pain Internet site (links to the journal Bandolier and is a key
resources for evidence-based practice in pain medicine)
(http://www.medicine.ox.ac.uk/bandolier/booth/painpag/index2.html)
other instances, laboratory tests may be required to uncover
a causative disease. For example, fasting blood test samples
may be useful in painful peripheral neuropathy. Sometimes
a diagnosis of neuropathic pain may suggest a need for
surgical treatment (e.g., to relieve a nerve entrapment); in
rare cases, this type of pain may be the first symptom of a
malignancy. If the sensory tests are inconclusive or the
causative disease is not evident, the patient should be re-
ferred to secondary care (e.g., a neurologic clinic or pain
clinic, according to local guidelines) for further assessment.
Tests used in a specialized center may include conventional
electrophysiologic procedures such as nerve conduction stud-
ies or somatosensory-evoked potentials, as well as less con-
ventional laboratory tools to assess the nociceptive pathways in
the peripheral and central nervous systems (Table 4).
Although these diagnostic procedures may be time con-
suming initially, they can result in improved efficiency over
the long term. Patient history and clinical examination are
the most important parts of the diagnosis, and may be accom-
plished over several primary care visits. Once an appropriate
diagnostic workup is completed, it may save time in future
primary care consultations. Management of pain may be easier
when both the patient and the physician are properly informed
about the nature of the problem. Selected educational resources
for physicians and patients are listed in Table 5.
Table 4 Laboratory Tests for Assessment of the Nociceptive
System
Method Explanation
Laser-evoked potentials Brain signals evoked by cutaneous
heat stimuli
Quantitative sensory Threshold measures of the perception
testing of various thermal and mechanical
cutaneous stimuli
Skin biopsies Punch biopsies to quantitatively
assess the number of nerve fibers
in the epidermis
For Patients and Caregivers
● British Pain Society (www.britishpainsociety.org/
patient_publications.htm)
● The Neuropathy Trust (www.neurocentre.com)
● American Chronic Pain Association (www.theacpa.org)
● Neuropathic Pain Network
(www.neuropathicpainnetwork.org)
● Action on Pain (www.action-on-pain.co.uk)
● American Pain Foundation (http://www.
painfoundation.org/)
CLINICAL CASE STUDIES
Two typical case studies are presented in which diagnosis
and successful treatment were achieved on the basis of
careful history and clinical examination.
Case 1
Presentation. A 47-year-old woman was diagnosed with a
malignant tumor in the left breast 8 months ago. The breast
was removed, as were axillary lymph nodes that were later
found to be devoid of cancerous infiltration. Immediately
after surgery, the patient reported pain in the anteromedial
aspect of the upper part of the thorax, the axilla, and the
medial aspect of the upper arm (Figure 1), a complaint that
is still current. The patient was not subjected to chemother-
apy or radiation.
At examination there was partial loss of sensation to
touch, cold, warmth, and pinprick testing in the entire pain-
ful area. Intercostobrachial neuralgia was diagnosed, and
the patient was started on treatment with amitriptyline,
titrated to 25 mg/day, resulting in a reduction in her pain
score of about 75%. During the titration period she com-
plained of dry mouth and fatigue, with the latter symptom
slowly vanishing over time.
Haanpää et al Assessment of Neuropathic Pain in Primary Care
Commentary. This case demonstrates neuropathic pain that
is neuroanatomically distributed in a way that corresponds
to the level of a peripheral nerve lesion, highlighting the
importance of a detailed pain drawing made by the patient
as part of the diagnostic workup. The outcome of the so-
matosensory examination with only loss of function, no
allodynia or hyperalgesia, is compatible with a neuropathic
condition. From a treatment perspective, the patient re-
ported excellent relief with amitriptyline, with only tran-
sient and tolerable side effects. As in other conditions,
achieving a balance between pain relief and side effects is
crucial in the pharmacologic treatment of neuropathic pain.
Case 2
Presentation. A 36-year-old woman was diagnosed with
HIV infection in 2001. In 2006, antiretroviral therapy was
instituted because of a high HIV viral load and a CD4 T-cell
count of ⬍200 ⫻ 106/L, although the patient had not yet
experienced an acquired immunodeficiency virus– defining
illness. The antiretroviral therapy regimen included treat-
ment with the nucleoside reverse transcriptase inhibitor
stavudine (d4T). After approximately 3 months of treat-
ment, the patient reported increasingly severe symptoms
indicative of a progressive bilateral sensory distal neuropa-
thy affecting both feet. Specifically, she described numb-
ness and paresthesias associated with a continuous burning
pain, the average intensity of which she rated as 6 of 10 on
an 11-point Likert scale (ranging from 0 to 10). The pain
was particularly severe at night. Sensory examination re-
vealed a loss of sensation to mechanical and heat stimuli
radiating down to the mid-calf level in both lower limbs,
although no deficits in motor function were evident. A
diagnosis of antiretroviral toxic neuropathy was made. The
physicians managing her HIV were requested by the pain
consultant to review the choice of antiretroviral therapy.
The change from stavudine, however, resulted in only a
slow and incomplete resolution of her neuropathy symp-
toms. Her pain was partially alleviated by gabapentin
therapy.53
Commentary. This case demonstrates painful toxic poly-
neuropathy caused by stavudine. Worsening of pain at night
is typical of painful polyneuropathy. In addition to cessation
of the toxic agent, symptomatic treatment with an anticon-
vulsant was needed.
SUMMARY
Neuropathic pain is a major public health problem and a
common, chronic, debilitating condition affecting patients
in primary care. Accurate diagnosis is a crucial first step
toward successful management and alleviation of discom-
fort and disability. Its presence is suggested by clinical
history and confirmed by physical examination. The differ-
ential diagnosis should reveal a location of pain that is
neuroanatomically logical, with evidence of abnormal so-
matosensory function, and determination of an underlying
S19
causative disease. Primary care physicians have a crucial
role to play in avoiding diagnostic delays and providing
appropriate assessment and management to improve out-
comes and reduce the human costs to patients and the
economic costs to society.
AUTHOR DISCLOSURES
The authors who contributed to this article have disclosed
the following industry relationships:
Maija L. Haanpää, MD, PhD, has worked as a consultant
to Janssen-Cilag EMEA, Orion, and Pfizer Inc.
Misha-Miroslav Backonja, MD, PhD, has served on the
Speakers’ Bureau for Eli Lilly and Company and Pfizer
Inc; has worked as a consultant to Allergan, Inc., Eli
Lilly and Company, Johnson & Johnson, Medtronic,
Inc., Merck & Co., Inc., NeurogesX, Pfizer Inc, and
UCB Pharma; and has received research/grant support
from Allergan, Inc., Eli Lilly and Company, Johnson &
Johnson, Merck & Co., Inc., and NeurogesX.
Michael I. Bennett, MB, ChB, has worked as a consultant
to Pfizer Inc.; and has received research/grant support
from Cephalon, Inc.
Didier Bouhassira, MD, PhD, has served on the Speakers’
Bureau for Eli Lilly and Company and Pfizer Inc; has
worked as a consultant to Eisai Inc., Eli Lilly and Com-
pany, Grünenthal, Johnson & Johnson, Newron Phar-
maceuticals, Pfizer Inc, Sanofi-Aventis, Sanofi Pasteur–
MSD, and Schering-Plough; and has received research/
grant support from Pfizer Inc.
Giorgio Cruccu, MD, PhD, has worked as a consultant to
Boehringer Ingelheim, Eli Lilly and Company, Medtronic,
Inc., Pfizer Inc, and UCB Pharma.
Per T. Hansson, MD, DMSc, DDS, reports no relation-
ships to disclose with any manufacturer of a product or
device discussed in this article.
Troels Staehelin Jensen, MD, PhD, has worked as a con-
sultant to Pfizer Inc.
Timo Kauppila, MD, PhD, has worked as a consultant to
Eli Lilly and Company, GlaxoSmithKline, Merck Sharp
& Dohme, Mundipharma, Orion, Pfizer Inc, Ratiopharm,
Nordic Drugs, and Sanofi Pasteur; has received honoraria
from Eli Lilly and Company, GlaxoSmithKline, Merck
Sharp & Dohme, Mundipharma, Orion, Pfizer Inc, Ratio-
pharm, Nordic Drugs, and Sanofi Pasteur; and has received
travel support from Merck Sharp & Dohme, Mundip-
harma, Pfizer Inc, and Sanofi Pasteur.
Andrew S. C. Rice, MB, BS, MD, FRCA, FFPMRCA,
(via Imperial College Consultants) has worked as a
consultant to Allergan, Inc., Astellas Pharma Europe
Ltd, Daiichi-Sankyo, Eisai Inc., GlaxoSmithKline,
Pfizer Inc, NeurogesX, and Spinifex Pharmaceuticals
Pty Limited; Allergan, Inc., Astellas, Daiichi-Sankyo,
Eisai Inc., GlaxoSmithKline, Pfizer Inc, NeurogesX,
and Spinifex Pharmaceuticals Pty Limited; and has re-
ceived research/grant support from Allergan, Inc., As-
tellas, Daiichi-Sankyo, Eisai Inc., GlaxoSmithKline,
S20 The American Journal of Medicine, Vol 122, No 10A, October 2009
Pfizer Inc, NeurogesX, and Spinifex Pharmaceuticals
Pty Limited.
Blair H. Smith, MB, ChD, MD, has worked as a consultant
to Napp Pharmaceuticals.
Rolf-Detlef Treede, Dr.med., has served on the advisory
boards of Allergan, Inc., Boehringer Ingelheim, Gl-
axoSmithKline, Grünenthal, Merck Sharp & Dohme,
Pfizer Inc, and UCB Pharma.
Ralf Baron, Dr.med., has worked as a consultant to Allergan,
Inc., Genzyme Corporation, Grünenthal, Medtronic, Inc.,
Mundipharma, Pfizer Inc, and Schwarz Pharma AG; and
has received research/grant support from Genzyme Corpo-
ration, Grünenthal, and Pfizer Inc.
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