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The IASP classification of chronic pain for ICD-11: chronic neuropathic pain.

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The upcoming 11th revision of the International Statistical Classification of Diseases and Related Health Problems (ICD) of the World Health Organization (WHO) offers a unique opportunity to improve the representation of painful disorders. For this purpose, the International Association for the Study of Pain (IASP) has convened an interdisciplinary task force of pain specialists. Here, we present the case for a reclassification of nervous system lesions or diseases associated with persistent or recurrent pain for ≥3 months. The new classification lists the most common conditions of peripheral neuropathic pain: trigeminal neuralgia, peripheral nerve injury, painful polyneuropathy, postherpetic neuralgia, and painful radiculopathy. Conditions of central neuropathic pain include pain caused by spinal cord or brain injury, poststroke pain, and pain associated with multiple sclerosis. Diseases not explicitly mentioned in the classification are captured in residual categories of ICD-11. Conditions of chronic neuropathic pain are either insufficiently defined or missing in the current version of the ICD, despite their prevalence and clinical importance. We provide the short definitions of diagnostic entities for which we submitted more detailed content models to the WHO. Definitions and content models were established in collaboration with the Classification Committee of the IASP's Neuropathic Pain Special Interest Group (NeuPSIG). Up to 10% of the general population experience neuropathic pain. The majority of these patients do not receive satisfactory relief with existing treatments. A precise classification of chronic neuropathic pain in ICD-11 is necessary to document this public health need and the therapeutic challenges related to chronic neuropathic pain.
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Narrative Review
The IASP classification of chronic pain for ICD-11:
chronic neuropathic pain
Joachim Scholz
a,b
, Nanna B. Finnerup
c,d
, Nadine Attal
e,f
, Qasim Aziz
g
, Ralf Baron
h
, Michael I. Bennett
i
,
Rafael Benoliel
j
, Milton Cohen
k
, Giorgio Cruccu
l
, Karen D. Davis
m,n
, Stefan Evers
o,p
, Michael First
q
,
Maria Adele Giamberardino
r
, Per Hansson
s,t
, Stein Kaasa
u,v,w
, Beatrice Korwisi
x
, Eva Kosek
y
,
Patricia Lavand’homme
z
, Michael Nicholas
aa
, Turo Nurmikko
bb
, Serge Perrot
cc
, Srinivasa N. Raja
dd
, Andrew S.
C. Rice
ee
, Michael C. Rowbotham
ff
, Stephan Schug
gg
, David M. Simpson
hh
, Blair H. Smith
ii
, Peter Svensson
jj,kk
,
Johan W.S. Vlaeyen
ll,mm
, Shuu-Jiun Wang
nn,oo
, Antonia Barke
x
, Winfried Rief
x
, Rolf-Detlef Treede
pp,
*, Classification
Committee of the Neuropathic Pain Special Interest Group (NeuPSIG)
Abstract
The upcoming 11th revision of the International Statistical Classification of Diseases and Related Health Problems (ICD) of the World
Health Organization (WHO) offers a unique opportunity to improve the representation of painful disorders. For this purpose, the
International Association for the Study of Pain (IASP) has convened an interdisciplinary task force of pain specialists. Here, we
present the case for a reclassification of nervous system lesions or diseases associated with persistent or recurrent pain for $3
months. The new classification lists the most common conditions of peripheral neuropathic pain: trigeminal neuralgia, peripheral
nerve injury, painful polyneuropathy, postherpetic neuralgia, and painful radiculopathy. Conditions of central neuropathic pain
include pain caused by spinal cord or brain injury, poststroke pain, and pain associated with multiple sclerosis. Diseases not explicitly
mentioned in the classification are captured in residual categories of ICD-11. Conditions of chronic neuropathic pain are either
insufficiently defined or missing in the current version of the ICD, despite their prevalence and clinical importance. We provide the
short definitions of diagnostic entities for which we submitted more detailed content models to the WHO. Definitions and content
models were established in collaboration with the Classification Committee of the IASP’s Neuropathic Pain Special Interest Group
(NeuPSIG). Up to 10% of the general population experience neuropathic pain. The majority of these patients do not receive
satisfactory relief with existing treatments. A precise classification of chronic neuropathic pain in ICD-11 is necessary to document
this public health need and the therapeutic challenges related to chronic neuropathic pain.
Keywords: Chronic pain, Neuropathic pain, Diagnosis, Classification, ICD-11, WHO
1. Neuropathic pain
Lesions or diseases involving the somatosensory nervous system
may paradoxically not only lead to a loss of function but also to
increased pain sensitivity and spontaneous pain. This neuro-
pathic pain is usually chronic, ie, it either persists continuously or
manifests with recurrent painful episodes. Pain may result from
etiologically diverse disorders affecting the peripheral or the
central nervous system. The cause can be a metabolic disease,
eg, diabetic neuropathy, a neurodegenerative, vascular or
autoimmune condition, a tumor, trauma, infection, exposure to
toxins, or a hereditary disease. Chronic pain also occurs in
neurological conditions of unknown etiology, eg, idiopathic
neuropathies.
5
The mechanistic underpinnings of pain hyper-
sensitivity and spontaneous pain in these conditions are complex,
and their relationship to the underlying pathological disease
process often remains unclear. On the other hand, differences in
pain phenotypes offer an opportunity to distinguish pain
syndromes clinically.
1,9,30
Neurophysiological investigations
may reveal some mechanistic clues, eg, activity increases in
somatosensory nerve fibers or changes in the endogenous
control of pain.
14,17
However, a lack of suitable noninvasive tests
usually precludes an in-depth evaluation of active pain mecha-
nisms in patients. Although imaging studies and quantitative
sensory tests help elucidate important pathophysiological
aspects of pain in patients, current knowledge of neuropathic
pain mechanisms is based largely on animal models.
Chronic neuropathic pain is a major factor contributing to the
global burden of disease.
21
Its prevalence ranges between 6.9%
and 10% of the general population.
28
How strongly pain is
associated with a particular neurological disease varies. Pain may
be the most prominent or sole disease manifestation as, eg, in
postherpetic neuralgia, or it may occur only in a subgroup of
patients with the same disease as, eg, in chemotherapy-induced
peripheral neuropathies. Even among patients with the same
underlying cause of neuropathic pain, painful symptoms and signs
usually differ.
4
However, when present, neuropathic pain frequently
causes major suffering and disability. Therapeutic management is
challenging. Medications recommended as first-line treatments
provide less than satisfactory relief in many patients.
11
A suspected diagnosis of neuropathic pain requires specific
investigations to ascertain that the pain originates in the nervous
system. The distribution of pain must correspond to the
underlying lesion or disease of the somatosensory nervous
system. The neuroanatomical relation to the underlying cause
must still be recognizable even if pain is not felt in the entire
innervation territory of an affected peripheral nerve or root, or the
somatotopic representation corresponding to a lesion or disease
of the central nervous system, or if pain extends somewhat
outside these boundaries. Objective signs of a sensory disorder in
January 2019·Volume 160 ·Number 1 www.painjournalonline.com 53
Copyright Ó2018 by the International Association for the Study of Pain. Unauthorized reproduction of this article is prohibited.
the distribution of pain increase diagnostic certainty. These signs
may indicate a sensory deficit or exaggerated responses to
normally painful (hyperalgesia) or painless stimuli (allodynia). The
definite diagnosis of neuropathic pain requires demonstration of
the cause, eg, neurophysiological tests confirming a peripheral
neuropathy or imaging results showing the involvement of
somatosensory fiber tracts after spinal cord injury.
6,10,25
Neuro-
pathic pain also requires specific treatment, involving both
pharmacological and nonpharmacological approaches.
8,11
Evi-
dence of high or moderate quality supports the use of
gabapentin, pregabalin, and inhibitors of serotonin and nor-
adrenalin reuptake, and tricyclic antidepressants as medications
of first choice. Dermal patches releasing lidocaine or capsaicin
and subcutaneous injection of botulinum toxin offer topical
treatment options. Opioids should be reserved for patients not
responding to therapeutic alternatives with a lower risk of adverse
effects.
11
Analgesics such as nonsteroidal anti-inflammatory
drugs have no proven efficacy against pain of neuropathic
origin.
18,29
These particular requirements for evaluation and
treatment call for an accurate representation of neuropathic pain
in diagnostic classifications of the relevant clinical conditions.
2. Shortcomings of ICD-10
A structured classification of conditions associated with neuropathic
pain is critically needed.
12
To date, the International Classification of
Headache Disorders (ICHD) is the only disease classification
providing systematic coverage of neuropathic pain conditions, but
these are limited to cranial nerve injuries and neuralgias.
12,15
Despite its clinical and economic significance, neuropathic
pain is not adequately represented in the current version of the
International Statistical Classification of Diseases and Related
Health Problems (ICD) of the World Health Organization (WHO).
The ICD is the most widely used source for diagnostic codes and
the standard instrument for disease classification in clinical
practice, epidemiology, and health management.
31
The ICD
organizes diseases and clinical syndromes by etiology, affected
organ, or body region. In the current version of the ICD (ICD-10),
painful conditions that do not fit this scheme can be classified as
acute (R52.0) or chronic pain (R52.2), with a separate code for
chronic intractable pain (R52.1). These codes can be combined
with neurological diagnoses, eg, diabetic polyneuropathy
(G63.2*). The asterisk behind the code indicates a clinical
syndrome in need of another etiological code, marked by
a dagger. In this example, type 2 diabetes mellitus with
neurological complications (E11.4†) would be a suitable speci-
fication. Thus, 3 codes are required to fully describe painful
diabetic polyneuropathy, one of the most common manifesta-
tions of neuropathic pain that affects up to 30% of patients with
type 2 diabetes.
3
There are very few explicit references to conditions of
neuropathic pain in ICD-10. They include trigeminal neuralgia
(G50.0), postzoster neuralgia (G53.0* B02.2†), and phantom limb
syndrome with pain (G54.6). The code for postzoster neuralgia,
better known as postherpetic neuralgia, applies only if the
disorder involves a cranial nerve, although thoracic nerve roots
are far more commonly affected by the disease.
24
Hereditary
neuropathies that are predominantly characterized by painful
symptoms or signs are not listed at all or incorrectly classified. For
example, erythromelalgia is designated as peripheral vascular
disease (I73.8) because painful episodes associated with the
disease are accompanied by an erythema. A hereditary variant of
the disease, in which intense pain, not reddening, is the leading
symptom, remains unspecified.
7
The complexity of ICD-10 codes and the incomplete or
inaccurate coverage of relevant clinical conditions risk
Sponsorships or competing interests that may be relevant to content are disclosed at the end of this article.
J. Scholz and N.B. Finnerup contributed equally to this manuscript. A. Barke, W. Rief, and R.-D. Treede contributed equally to this manuscript.
Departments of
a
Anesthesiology and,
b
Pharmacology, Columbia University Medical Center, New York, NY, United States,
c
Department of Clinical Medicine, Danish Pain
Research Center, Aarhus University, Aarhus, Denmark,
d
Department of Neurology, Aarhus University Hospital, Aarhus, Denmark,
e
INSERM U 987, Assistance
Publique—H ˆopitaux de Paris, H ˆopital Ambroise Par ´e, Boulogne Billancourt, France,
f
Universit ´e Versailles Saint Quentin en Yvelines, Versailles, France,
g
Centre for
Neuroscience and Trauma, Wingate Institute of Neurogastroenterology, Blizard Institute, Barts and The London School of Medicine and Dentistry, Queen Mary University of
London, London, United Kingdom,
h
Department of Neurology, Universit¨atsklinikum Schleswig-Holstein, Kiel, Germany,
i
Academic Unit of Palliative Care, University of
Leeds, Leeds, United Kingdom,
j
Department of Diagnostic Sciences, Rutgers School of Dental Medicine, Newark, NJ, United States,
k
St. Vincent’s Clinical School,
University of New South Wales, Sydney, Australia,
l
Department of Human Neuroscience, Sapienza University, Rome, Italy,
m
Department of Surgery and Institute of Medical
Science, University of Toronto, Toronto, ON, Canada,
n
Division of Brain, Imaging and Behavior-Systems Neuroscience, Krembil Research Institute, Univer sity Health
Network, Toronto, ON, Canada,
o
Department of Neurology, Krankenhaus Lindenbrunn, Coppenbr ¨ugge, Germany,
p
Faculty of Medicine, University of M ¨unster, M ¨unster,
Germany,
q
Department of Psychiatry, Columbia University, New York State Psychiatric Institute, New York, NY, United States,
r
Department of Medicine and Science of
Aging, CeSI-MeT, G D’Annunzio University of Chieti, Chieti, Italy,
s
Department of Pain Management and Research, Division of Emergencies and Critical Care, Oslo University
Hospital, Oslo, Norway,
t
Department of Molecular Medicine and Surgery, Karolinska Institutet, Stockh olm, Sweden,
u
European Palliative Care Research Centre (PRC), Oslo,
Norway,
v
Department of Oncology, Oslo University Hospital, Oslo, Norway,
w
Institute of Clinical Medicine, University of Oslo, O slo, Norway,
x
Division of Clinical Psychology
and Psychotherapy, Department of Psychology, Philipps-University Marburg, Marburg, Germany,
y
Department of Clinical Neuroscience, Karolinska Institute, Stockholm,
Sweden,
z
Department of Anesthesiology and Acute Postoperative Pain Service, Saint Luc Hospital, Catholic University of Louvain, Bruss els, Belgium,
aa
Pain Management
Research Institute, Royal North Shore Hospital, University of Sydney, Sydney, Australia,
bb
Institute of Aging and Chronic Disease, University of Liverpool, Liverpool, United
Kingdom,
cc
INSERM U 987, Pain Clinic, Cochin Hospital, Paris Descartes University, Paris, France,
dd
Division of Pain Medicine, Department of Anesthesiology and Critical
Care Medicine, Johns Hopkins University School of Medicine, Baltimore, MD, United States,
ee
Pain Research, Department of Surgery and Cancer, Imperial College, London,
United Kingdom,
ff
California Pacific Medical Center Research Institute, San Francisco, CA, Uni ted States,
gg
Anaesthesiology and Pain Medicine, Medical School, University
of Western Australia and Royal Perth Hospital, Perth, Australia,
hh
Department of Neurology, Icahn School of Medicine at Mount Sinai, New York, NY, United States,
ii
Division
of Population Health and Genomics, University of Dundee, Dundee, Scotland,
jj
Section of Clinical Oral Physiology, School of Dentistry, Aarhus University, Aarhus, Denmark,
kk
Department of Dental Medicine, Karolinska Institute, Huddinge, Sweden,
ll
Research Group Health Psychology, University of Leuven, Leuven, Belgium,
mm
Experimental
Health Psychology, Maastricht University, Maastricht, the Netherlands,
nn
Neurological Institute, Taipei Veterans General Hospital, Taipei, Taiwan,
oo
Brain Research Center,
National Yang-Ming University, Taipei, Taiwan,
pp
Department of Neurophysiology, CBTM, Medical Faculty Mannheim of Heidelberg University, Mannheim, Germany
*Corresponding author. Department of Neurophysiology, Centre for Biomedicine and Medical Technology Mannheim, Medical Faculty Mannheim, Heidelberg University,
Ludolf-Krehl-Str.13-17, 68167 Mannheim, Germany. Tel.: 149 (0)621 383 71 400; fax: 149-(0)621 383 71 401.E-mail address: Rolf-Detlef.Treede@medma.uni-heidelberg.
de (R.-D. Treede).
Supplemental digital content is available for this article. Direct URL citations appear in the printed text and are provided in the HTML and PDF versions of this article on the
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PAIN 160 (2019) 53–59
©2018 International Association for the Study of Pain
http://dx.doi.org/10.1097/j.pain.0000000000001365
54 J. Scholz et al.·160 (2019) 53–59 PAIN
®
Copyright Ó2018 by the International Association for the Study of Pain. Unauthorized reproduction of this article is prohibited.
underreporting of chronic pain. This has practical consequences
for clinicians, hospitals, and other health care providers. Under-
reporting also hinders efficient resource management by insurers
and the development of sound public health strategies by
policymakers. The current epidemic of opioid abuse in North
America illustrates the importance of a reliable classification of
chronic pain to enable the monitoring of safe and effective
analgesics use in cancer and noncancer pain, including pain of
neuropathic origin.
13
3. The IASP Task Force Initiative for the classification
of chronic pain in the International Classification
of Diseases
To generate a systematic and improved classification of conditions
associated with clinically relevantpain and to ensure representation
of these diagnoses in the upcoming revision of the ICD, the
International Association for the Study of Pain (IASP) established
a Task Force that works in close cooperation with WHO
representatives.
27
The classification is dedicated exclusively to
chronic pain syndromes, defined as persistent or recurrent pain
lasting $3 months. As we have previously outlined, conditions of
neuropathic pain are divided into 2 broad categories for peripheral
or central nervous disorders. Diseases not explicitly listed in the
classification will be captured in residual categories.
27
During the
process of drafting and editing the definitions of individual diseases
and detailed content models of neuropathic pain, the Task Force
conferred with the Classification Committee of the IASP’s
Neuropathic Pain Special Interest Group (NeuPSIG). Content
models underwent initial field testing in Australia, Germany, Japan,
and Norway. Revised models were subjected to further field testing
by the WHO in WHO-led field tests. We will report the results of
these field tests separately. Overall, utility and specificity of the
diagnostic criteria were ranked highly. A version for preparing
implementation of ICD-11 was released by the WHO in June
2018.
32
The complete revision will be submitted to the WHO’s
Executive Board in January and the World Health Assembly in May
2019. After endorsement, member states are expected to report
health statistics according to ICD-11 from 2022 onward.
4. The classification of chronic neuropathic pain
Some conditions of persistent neuropathic pain produce distinct
symptoms that would allow for diagnosing chronic pain before the
3-month threshold. One example is trigeminal neuralgia, which is
characterized by a pain distribution in one or more branches of the
fifth cranial nerve, abrupt pain paroxysms, and provocation of
these pain attacks by normally innocuous mechanical stimuli or
orofacial movements. Periods of remission vary, but the neuralgia
never disappears completely.
6,15
Similarly, pain associated with
polyneuropathy caused by type 2 diabetes or central pain after
spinal cord injury usually persists sothat it may seem unnecessary
to wait 3 months before diagnosing chronic neuropathic pain.
3,23
Nonetheless, in the absence of objective markers delineating
acute and chronic phases of pain, the arbitrary definition of 3
months was chosen because it provides for clear operationaliza-
tion in line with widely used research criteria and subject enrolment
in analgesic treatment trials.
26
The proposed classification differentiates neuropathic pain of
peripheral and central origin.
16
It comprises 9 common con-
ditions associated with persistent or recurrent pain (Fig. 1 and
supplementary Table 1, available at http://links.lww.com/PAIN/
A658). Short definitions of these conditions are listed below.
These definitions are part of more detailed content models
included in the so-called foundation layer of ICD-11. The models
provide minimum criteria of possible neuropathic pain and
describe investigations that support a definitive diagnosis.
6,10
They also contain extension codes for pain severity (combining
intensity, distress, and disability), temporal characteristics, and
psychological or social factors,
26
as well as a link to the
International Classification of Functioning (ICF).
19,33
4.1. Chronic neuropathic pain
Chronic neuropathic pain is chronic pain caused by a lesion or
disease of the somatosensory nervous system.
16
The pain may
be spontaneous or evoked, as an increased response to a painful
stimulus (hyperalgesia) or a painful response to a normally
nonpainful stimulus (allodynia). The diagnosis of chronic neuro-
pathic pain requires a history of nervous system injury or disease
and a neuroanatomically plausible distribution of the pain.
Negative (eg, decreased or loss of sensation) and positive
sensory symptoms or signs (eg, allodynia or hyperalgesia)
indicating the involvement of the somatosensory nervous system
must be compatible with the innervation territory of the affected
nervous structure. These criteria apply to all diagnostic entities of
chronic neuropathic pain.
4.1.1. Chronic peripheral neuropathic pain
Chronic peripheral neuropathic pain is chronic pain caused by
a lesion or disease of the peripheral somatosensory nervous
system.
4.1.1.1. Trigeminal neuralgia
Trigeminal neuralgia is a manifestation of orofacial neuropathic
pain restricted to one or more divisions of the trigeminal nerve.
The pain is recurrent, abrupt in onset and termination, triggered
by innocuous stimuli, and typically compared with an electric
shock or described as shooting or stabbing. Some patients
experience continuous pain between these painful paroxysms.
The diagnosis comprises idiopathic trigeminal neuralgia,
classical neuralgia produced by vascular compression of the
trigeminal nerve, and secondary neuralgia caused by a tumor or
cyst at the cerebellopontine angle or multiple sclerosis.
6
As for other conditions of chronic neuropathic pain, the
detailed content model includes a discussion of the etiology.
4.1.1.2. Chronic neuropathic pain after peripheral nerve
injury
Chronic neuropathic pain after peripheral nerve injury is persistent
or recurrent pain caused by a peripheral nerve lesion. History of
a plausible nerve trauma, pain onset in temporal relation to the
trauma, and pain distribution within the innervation territory of
a peripheral nerve (or nerves) are required for the diagnosis.
Negative and positive sensory symptoms or signs must be
compatible with the innervation territory of the affected nerve (or
nerves). Formation of a neuroma may lead to pain at the lesion site.
Consistent with the new concept of “multiple parenting” in ICD-
11 (Fig. 1), the diagnosis of chronic neuropathic pain after
peripheral nerve injury is also listed in the section on postsurgical
and posttraumatic pain.
22
However, the content model for the
diagnosis is stored in the foundation layer of ICD-11.This
hierarchical structure of the classification allows for multiple
referencing of a content model without duplicating the diagnosis.
January 2019·Volume 160 ·Number 1 www.painjournalonline.com 55
Copyright Ó2018 by the International Association for the Study of Pain. Unauthorized reproduction of this article is prohibited.
4.1.1.3. Painful polyneuropathy
Chronic pain occurs in polyneuropathies caused by metabolic,
autoimmune, familial or infectious diseases, exposure to environ-
mental or occupational toxins, or treatment with a neurotoxic drug.
Chronic pain also occurs in polyneuropathies of unknown etiology.
Pain may be the initial symptom of a neuropathy or develop over the
course of the disease (Case vignette 1). Negative and positive sensory
symptoms or signs must be compatible with the anatomical
distribution pattern of the polyneuropathy. Chemotherapy-induced
peripheral neuropathy is one form of painful polyneuropathy included
in the classification of chronic cancer-related pain.
2
4.1.1.4. Postherpetic neuralgia
Postherpetic neuralgia is defined as pain persisting for $3
months after the onset or healing of herpes zoster. The
innervation territory of the first (ophthalmic) branch of the
Figure 1. Classification of chronic neuropathic pain in ICD-11. Top and 2nd level diagnoses are part of ICD-11 Mortality and Morbidity Linearisation (MMS).
32
Specific entities of chronic neuropathic pain are included at the next level. According to the new concept of multiple parenting in ICD-11, these entities may be
referred to from other divisions of the chronic pain classification, eg, chronic posttraumatic pain or chronic secondary headaches and orofacial pains.
56 J. Scholz et al.·160 (2019) 53–59 PAIN
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Copyright Ó2018 by the International Association for the Study of Pain. Unauthorized reproduction of this article is prohibited.
trigeminal nerve and thoracic dermatomes are the locations most
frequently affected by chronic pain after herpes zoster. Post-
herpetic neuralgia may emerge in continuation of the acute pain
associated with the skin rash or develop after a painless interval.
Negative and positive sensory symptoms or signs must be
compatible with the innervation territory of the affected cranial
nerve or peripheral dermatome (or dermatomes).
4.1.1.5. Painful radiculopathy
Chronic painful radiculopathy is persistent or recurrent pain caused
by a lesion or disease involving the cervical, thoracic, lumbar, or
sacral nerve roots. Degenerative changes of the spinal column
including ligaments and intervertebral disks are the most frequent
cause, but painful radiculopathy may also result from trauma, tumor,
or neoplastic meningitis, from infections, hemorrhage or ischemia,
diabetes mellitus, rheumatoid arthritis, or from an iatrogenic lesion,
eg, during injection therapy or surgery. Pain within the affected
dermatomes (radicular pain) is required for the diagnosis. The pain
may be spontaneous but is typically exacerbated or provoked by
taking or maintaining a certain body position or during movement.
Negative and positive sensory symptoms or signs must be
compatible with the innervation territory of the affected nerve root
(or roots). Musculoskeletal pain associated with painful radiculop-
athy should be classified separately.
20
4.1.1.6. Other specified and unspecified chronic peripheral
neuropathic pain
ICD-11 contains a residual category for other specified conditions
of chronic peripheral neuropathic pain that are not covered by the
diseases listed above, eg, chronic neuropathic pain caused by
a carpal tunnel syndrome. An additional category for unspecified
conditions provides for the classification of disorders for which
insufficient information is available to assign a precise diagnosis.
4.1.2. Chronic central neuropathic pain
Chronic central neuropathic pain is chronic pain caused by
a lesion or disease of the central somatosensory nervous system.
4.1.2.1. Chronic central neuropathic pain associated with
spinal cord injury
Chronic central neuropathic pain associated with spinal cord
injury is caused by a lesion or disease of the somatosensory
pathways in the spinal cord. The definition of spinal cord injury
comprises impairments of spinal cord function resulting from
external force or a disease process. The pain may be
spontaneous or evoked, as an increased response to a painful
stimulus (hyperalgesia) or a painful response to a normally
nonpainful stimulus (allodynia). The diagnosis requires a history of
spinal cord lesion or disease and a neuroanatomically plausible
distribution of the pain, ie, pain felt in dermatomes at or below the
level of injury in areas with sensory disturbance (Case vignette 2).
This cause of central neuropathic pain is also included in the
classification of chronic postsurgical and posttraumatic pain.
22
4.1.2.2. Chronic central neuropathic pain associated with
brain injury
Chronic central neuropathic pain associated with brain injury is
caused by a lesion or disease of the somatosensory cortex,
connected brain regions, or associated pathways in the brain.
History of a plausible brain trauma, pain onset in temporal relation
to the trauma, and a pain distribution that is neuroanatomically
plausible are required for the diagnosis. Negative or positive
sensory symptoms or signs indicating the involvement of the brain
must be present in the body region corresponding to the brain
injury.
See also the classification of chronic postsurgical and post-
traumatic pain.
22
4.1.2.3. Chronic central poststroke pain
Chronic central poststroke pain is caused by a cerebrovascular
lesion, infarct or hemorrhage, of the brain or brainstem. The pain
may be spontaneous or evoked, as an increased response to
a painful stimulus (hyperalgesia) or a painful response to
a normally nonpainful stimulus (allodynia). The diagnosis of
central poststroke pain requires a history of stroke and a neuro-
anatomically plausible distribution of the pain, ie, pain felt in the
body region represented in the central nervous structures
affected by the stroke. Negative or positive sensory symptoms
or signs indicating the involvement of the brain must be present in
the body region affected by the stroke.
4.1.2.4. Chronic central neuropathic pain caused by multiple
sclerosis
Chronic central neuropathic pain in multiple sclerosis is caused
by a lesion of somatosensory brain regions or their connecting
Case vignette 1: Chronic painful polyneuropathy
A 56-year-old woman with type 2 diabetes mellitus for 2 years complains about pain in the feet that started approximately 4 months ago. The pain intensity is 5 to 7 on a scale from
0 to 10. The pain may get worse at night or when she is walking. In addition, she noticed numbness and tingling in the feet. The examination reveals a stocking-like distribution of
deficits in the sense of touch. The Achilles tendon reflex is weak. An electrophysiological examination shows slow conduction in the sural and peroneal nerves. The patient has
a body mass index of 30. Her fasting blood glucose concentration is 132 mg/dL, and the HbA1 measures 7%. Painful polyneuropathy caused by type 2 diabetes mellitus was
diagnosed. The treatment plan consisted of improved blood glucose management, medication for neuropathic pain, and foot care education.
Case vignette 2: Chronic central neuropathic pain associated with spinal cord injury
A 40-year-old man, who 5 years ago suffered an incomplete spinal cord injury at the thoracic level, reports diffuse pain in both legs. He desc ribes an ongoing pain of burning
and squeezing character as well as sensations of pins and needles. The average pain intensity is 6/10. In addition, he sometimes experiences pain provoked by light touch.
These painful sensations developed gradually over the first 6 months after the injury. On physical examination, he exhibits decreased detection of both mechanical and
thermal stimuli from dermatome T4 down, hypersensitivity to cold and touch-evoked allodynia on the lower legs. The diagnosis was chronic central neuropathic pain
associated with spinal cord injury. Following referral to a multidisciplinary center for pain therapy, he received comprehensive care including medication for neuropathic
pain, physical and cognitive behavioral therapy.
January 2019·Volume 160 ·Number 1 www.painjournalonline.com 57
Copyright Ó2018 by the International Association for the Study of Pain. Unauthorized reproduction of this article is prohibited.
pathways. The pain may be spontaneous or evoked, as an
increased response to a painful stimulus (hyperalgesia) or a painful
response to a normally nonpainful stimulus (allodynia). The
diagnosis requires a history of multiple sclerosis and a neuro-
anatomically plausible distribution of the pain. Negative or positive
sensory symptoms or signs indicating the involvement of the brain
or spinal cord must be present in the area of the body affected by
pain. Pain primarily related to spasticity should be classified as
musculoskeletal pain.
20
4.1.2.5. Other specified and unspecified chronic central
neuropathic pain
Residual categories are available for other specified or un-
specified conditions of chronic central neuropathic pain.
5. Discussion
Neuropathic pain commonly persists beyond the natural healing
process of the underlying disease, eg, in postherpetic neuralgia,
or despite treatment directed at the disease cause. Combining
a code for the underlying disease with the explicit diagnosis of
neuropathic pain has the advantage that for the first time, patients
with specific treatment needs for their pain will be distinguished
from those with a painless manifestation of the same neurological
disorder. Although the neurological diagnosis will guide treatment
of the disease that is responsible for the pain, the neuropathic
pain diagnosis will provide for appropriate pain management.
Different from previous editions of the ICD, the new codes for
chronic neuropathic pain will be concise and embedded in
a systematic classification of chronic pain. They will cover the
epidemiologically most relevant conditions and provide clear
diagnostic criteria that are backed by literature references and
suggestions for additional investigations to increase the level of
diagnostic certainty.
ICD-11 includes cross-references to other conditions of
chronic pain in separate “parent” chapters. Examples are painful
chemotherapy-induced polyneuropathy, which are mentioned
under chronic cancer-related pain,
2
or pain after amputation,
which are listed under chronic postsurgical and posttraumatic
pain.
22
Cross-referencing in ICD-11 facilitates the coding of
painful disorders within the most fitting treatment-relevant
category of the classification.
The proposed classification is a compromise balancing the
length of this important division with those of 6 other groups of
chronic pain conditions, eg, musculoskeletal and visceral pain.
Diseases not explicitly listed in the classification are captured in
residual categories for “Other specified chronic peripheral neuro-
pathic pain” or “Other specified chronic central neuropathic pain.”
6. Summary and conclusions
The classification of chronic neuropathic pain represents the first
systematic and most comprehensive classification to date of
common painful neurological disorders. Precise diagnostic
criteria and literature references are included in the full-content
description of the disorders to minimize ambiguity. The criteria
match the grading system for evidence supporting the diagnosis
of neuropathic pain in clinical practice and research.
11
These
provisions generate a valuable tool for diagnostic code assign-
ment, appropriate allocation of health care services, and the
collection of epidemiological data. Clear definitions combined
with a seamless evaluation of the evidence leading to the
diagnosis of chronic neuropathic pain will facilitate patient
identification for enrolment in clinical trials and promote the
translation of research findings into practice.
Conflict of interest statement
J. Scholz has received research support from the Thompson Family
Foundation and Acetylon, and is now an employee of Biogen. This
work was completed before he joined the company. Biogen did not
have a role in the design, conduct, analysis, interpretation, or funding
of the research related to this work. N.B. Finnerup has received
honoraria for serving on advisory boards or speaker panels from
Astellas, Gr ¨unenthal, Mitshubishi Tanabe, Novartis, and Teva. N.
Attal has received speaker fees from Pfizer and consultant fees from
Aptinyx, Gr ¨unenthal, Mundipharma, Novartis, Sanofi Pasteur, and
Teva. R. Baron reports receiving research grants from Genzyme,
Gr ¨unenthal, Mundipharma, and Pfizer, and honoraria for serving on
advisory boards or speakers panels from Abbvie, Allergan, Astellas,
AstraZeneca, Bayer, Biogen, Biotest, Boehringer Ingelheim, Bristol-
Myers Squibb, Daiichi Sankyo, Desitin, Eisai, Galapagos NV,
Genentech, Genzyme, Glenmark, Gr ¨unenthal, Kyowa Kirin, Lilly,
Medtronic, Merck MSD, Mundipharma, Novartis, Pfizer, Sanofi
Pasteur, Seqirus, TAD, Teva, and Vertex. He is also member of the
Innovative Medicines Initiative (IMI), a public–private partnership
between the European Union and the European Federation of
Pharmaceutical Industries and Associations (EFPIA). G. Cruccu
reports grants or personal fees from Alfa sigma, Angelini, Biogen,
Mundipharma, and Pfizer. M. First reports personal fees from
Lundbeck International Neuroscience Foundation, outside the
submitted work. M.A. Giamberardino reports personal fees from
IBSA Institute Biochimique, personal fees from EPITECH Group,
personal fees from Helsinn Healthcare, grants from EPITECH Group,
and grants from Helsinn Healthcare, outside the submitted work. S.
Kaasa reports that he is Eir solution—stockholder. T. Nurmikko has
received personal fees from Abide, Astellas, Mundipharma, and
Nexstim. S.N. Raja has received research grants from Medtronic,
and serves in the advisory boards of Allergan, Daiichi Sankyo, and
Aptinyx. A.S.C. Rice has received research funding from Orion, has
consulted or participated in advisory boards for Imperial College
Consultants, including remunerated work for Abide, Astellas,
Galapagos, Lateral, Peter McNaughton from King’s College London
and Cambridge University, Merck, Mitsubishi, Novartis, Orion,
Pharmaleads, Quartet, and Toray. He owned share options in
Spinifex from which personal benefit accrued upon the acquisition
of Spinifex by Novartis, and from which future milestone payments
may occur. A.S.C. Rice is also named inventor on patents WO
2005/079771, EP13702262.0, and WO2013/110945. S.A. Schug:
The Discipline of Anaesthesiology and Pain Medicine at the
University of Western Australia, but not S.A. Schug personally,
has received research and travel funding and speaking and
consulting honoraria from Andros Pharmaceuticals, Aspen, bioCSL,
Eli Lilly, Grunenthal, Invidior, Janssen, Luye Pharma, Mundipharma,
Pfizer, Pierre Fabre, Seqirus and iX Biopharma, outside the
submitted work. S.-J. Wang reports personal fees from Eli-Lilly,
personal fees from Daiichi Sankyo, grants and personal fees from
Pfizer, Taiwan, personal fees from Eisai, personal fees from Bayer,
and personal fees from Boehringer Ingelheim, outside the submitted
work. A. Barke reports personal fees from IASP, during the conduct
of the study. W. Rief reports grants from IASP, during the conduct of
the study; personal fees from Heel, personal fees from Berlin
Chemie, outside the submitted work. R.-D. Treede reports grants
from Boehringer Ingelheim, Astellas, AbbVie, and Bayer, personal
fees from Astellas, Gr ¨unenthal, Bauerfeind, Hydra, and Bayer,
grants from EU, DFG, and BMBF, outside the submitted work. The
remaining authors have no conflicts of interest to declare.
58 J. Scholz et al.·160 (2019) 53–59 PAIN
®
Copyright Ó2018 by the International Association for the Study of Pain. Unauthorized reproduction of this article is prohibited.
Acknowledgements
The authors gratefully acknowledge financial support by the IASP
and the excellent discussions with Dr. Robert Jakob of the WHO.
Members of the Taskforce: Rolf-Detlef Treede (Chair), Winfried
Rief (Co-chair), Antonia Barke, Qasim Aziz, Michael I. Bennett,
Rafael Benoliel, Milton Cohen, Stefan Evers, Nanna B. Finnerup,
Michael First, Maria Adele Giamberardino, Stein Kaasa, Beatrice
Korwisi, Eva Kosek, Patricia Lavand’homme, Michael Nicholas,
Serge Perrot, Joachim Scholz, Stephan Schug, Blair H. Smith,
Peter Svensson, Johannes Vlaeyen, Shuu-Jiun Wang.
Appendix A. Supplemental digital content
Supplemental digital content associated with this article can be
found online at http://links.lww.com/PAIN/A658. SDC includes
a complete reference list of the diagnoses entered into the
foundation with the foundation IDs as well as the extension codes
(specifier). Since the complete list is contained, the material is
identical for all papers of the series.
Article history:
Received 14 June 2018
Received in revised form 25 July 2018
Accepted 30 July 2018
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January 2019·Volume 160 ·Number 1 www.painjournalonline.com 59
Copyright Ó2018 by the International Association for the Study of Pain. Unauthorized reproduction of this article is prohibited.
... Chronic pain was defined as pain lasting longer than three months, leading to functional and/or psychological impairment (consistent with the definition provided by the International Association for the Study of Pain). 8 Opioid tolerance was defined as opioid use on most days for more than 3 months. 9 Patients with chronic pain and opioid tolerance were identified from the electronic medical record (EMR) based on available information (including documentation in the medical history, medication history, and clinical notes following preoperative review/evaluation by a member of the HSS Perioperative Pain Service). ...
... Chronic pain, defined as pain persisting beyond normal tissue healing time (>3 months), presents a substantial global health burden, characterized by significant suffering and disability. 8 Complex peripheral and central sensitization processes occur in nociceptors, dorsal root ganglia, the spinal cord, and cerebral cognitive and emotional centers. These processes involve the upregulation of receptors and signaling molecules implicated in pain perception, and alterations in nerve fiber responsiveness and neurotransmitter release, leading to lowered pain thresholds and increased sensitivity to pain stimuli. ...
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