Download Neuropathic pain: a pathway for care developed

British Journal of Anaesthesia 111 (1): 73–9 (2013)
doi:10.1093/bja/aet206
Neuropathic pain: a pathway for care developed by the British
Pain Society
B. H. Smith 1*, J. Lee 2,3, C. Price 4 and A. P. Baranowski 3,5
1
Division of Population Health Sciences, Ninewells Hospital & Medical School, University of Dundee, Dundee DD2 4DB, UK
Specialist in Pain Medicine, Cayman Islands Hospital, University College London, PO Box 915, Grand Cayman KY1-1103, London, UK
3
University College London, London, UK
4
Pain Clinic, University Hospital of Southampton, Tremona Road, Southampton, Hampshire SO16 6YD, UK
5
Pain Management Centre, National Hospital for Neurology & Neurosurgery, Queen Square, London WC1N 3BG, UK
2
* Corresponding author. E-mail: [email protected]
Editor’s key points
† Neuropathic pain is a
challenging pain syndrome to
treat effectively.
† Diagnosis of neuropathic pain
can be ‘possible’, ‘probable’, or
‘definite’, all potentially
requiring treatment.
† This review outlines a new
practical guideline to the
comprehensive management of
neuropathic pain.
† The current evidence base has
clear research gaps that need to
be addressed.
Summary. Neuropathic pain is a common chronic pain condition that can be challenging
to treat, particularly for non-specialists. The development of the Map of Medicine care
pathway for the management of neuropathic pain was led by the British Pain Society.
Focusing on treatment by non-specialists, this pathway is based on new evidence,
consensus, and the interests of service users. This paper presents the care pathway
and accompanying evidence base, highlighting its salient features, and discussing
important treatment points. After initial assessment, the pathway progresses through
first-, second-, and third-line drug treatment, includes advice on topical treatment
and opioids (in specific circumstances), and describes non-pharmacological
approaches. Importantly, timely review of patients and referral to specialist
secondary or tertiary care must be considered as vital components of the pathway.
Although the emphasis was not on specialist treatment, advice is given on existing
interventions, including neural stimulation and multi-disciplinary care. These, and
other steps on the pathway, will be subject to further review as more evidence
becomes available. In the meantime, the pathway represents a straightforward,
valuable and accessible approach for healthcare professionals managing the distress
and impact of neuropathic pain.
Keywords: nerve pain; neuralgia; neuropathic pain
The British Pain Society (BPS) is a national society, affiliated
with the International Association for the Study of Pain
(IASP). It has commissioned working groups to develop five
care pathways for pain to assist the management of
common pain conditions. The pathways are intended to be
comprehensive and to maximize generalist care, and each
has an accompanying commentary. They are: the initial assessment and early management of pain;1 chronic widespread
pain, including fibromyalgia;2 low back, and radicular pain;3
pelvic pain;4 and neuropathic pain5 (presented here). They
can be viewed on the BPS website. The pathways were
chosen because of the high frequency of presentation with
the problem, geographical variability in access to treatment,
variation in clinical case management, or a combination of
some or all of these issues.
Neuropathic pain
Chronic pain has been shown to affect up to 46% of the adult
population, with .5% reporting high intensity, severely disabling chronic pain.6 7 The recent Health Survey for England found
that 31% of men, and 37% of women reported chronic pain.8
Neuropathic pain, defined by the IASP as ‘pain arising as a
direct consequence of a lesion or disease affecting the somatosensory system’,9 was previously thought to affect 1% of the UK
population,10 but more recent research suggests that this
figure is closer to 8%.11 This increase is due in part to the recognition that neuropathic mechanisms contribute to many types
of chronic pain, and therefore that ‘classic’ neuropathic pain
diagnoses (Table 1) only represent a small proportion of the
problem in the population. It is also likely that patients and professionals are more aware of the possibility of neuropathic pain
than they were, perhaps because of greater availability of specific, effective treatments, and educational initiatives surrounding these.
Neuropathic pain is a particularly unpleasant type of pain,
whose characteristics contribute to poor general health, and
produce quality of life scores similar to those reported by
people with serious mental illness, or with severe heart
disease.12 13 In common with other chronic conditions, it is
commoner among women and in relative deprivation. The
ageing population and rising prevalence of specific risk
factors (notably diabetes)14 mean that neuropathic pain will
increase both in incidence and prevalence, and it is important
& The Author [2013]. Published by Oxford University Press on behalf of the British Journal of Anaesthesia. All rights reserved.
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BJA
Table 1 Common causes of neuropathic pain
Peripheral
Painful diabetic neuralgia
Post-herpetic neuralgia
Trigeminal neuralgia
Lumbar radiculopathy
Nerve damage, including postoperative
Pain because of cancer tumour infiltration
Central
Post-stroke pain
Multiple sclerosis
Chemotherapy-induced pain
General
Idiopathic
Smith et al.
entity (present/absent), the diagnosis of which relied on
detailed neurological assessment, we now acknowledge the
existence of ‘possible’, ‘probable’, and ‘definite’ neuropathic
pain.9 Although still requiring skilled clinical history and examination, the diagnosis of ‘possible’ neuropathic pain requires
less time and specialist clinical skill, and is therefore easier in
brief primary care consultations. The presence of a few
typical symptoms and easily observed signs, with a neuroanatomically logical potential cause, is sufficient for the
non-specialist to take the first steps towards successful management, using available guidelines.17 In this way, gauging
response to early, specific treatments, reduces suffering, and
assists diagnosis, often without the need for the detailed assessment that might be required to diagnose ‘definite’ neuropathic pain.
Neuropathic contributions to other painful conditions
therefore that non-specialist health professionals have a
robust, evidence-based approach to its management.
Excellent recent systematic reviews have assessed the evidence for pharmacological treatment of neuropathic pain,
concluding that there are many specific effective medicines
available.15 16 Other systematic approaches have produced
evidence-based consensus approaches to the assessment of
neuropathic pain, in both primary care,17 and other settings.18
Despite this, there is consistent evidence of under-recognition,
under-treatment of neuropathic pain, or both, particularly in
primary care.19 20 Hall and colleagues, in a 2005 review of
common neuropathic pain conditions using the General Practice Research Database, found that the most commonly prescribed items were the same across conditions, and included
opioids as first-line treatments. However, changes in therapy
were less frequent when initial therapy was with antidepressants or anticonvulsants rather than conventional analgesics,
confirming the relative effectiveness of these drugs in primary
care.21 Therefore, there is a need for accessible guidance for
non-specialists, to help them to improve the health and
quality of life of their patients with the best approaches to
treating this common and disabling condition.
With all guidelines, the most important step in achieving the
intended outcome is the first one having identified its relevance (i.e. setting off on the correct pathway). This is the
stage at which undifferentiated illness (as usually presented
in primary care) takes on shape and form, achieves definition,
and moves towards diagnosis and management. This is particularly true for neuropathic pain, recognition of which (as distinct from non-neuropathic pain) leads to the use of effective
treatments and the avoidance of some ineffective ones.
Along the way, this is likely to lead to the maximum clinical
benefit, with the minimal harm. Arguably, therefore, the
most important activities associated with good quality guidelines are those that promote awareness of their existence,
enhance their accessibility, or both.
The recent re-classification of neuropathic pain by the IASP,
now makes this first step easier. Previously, a binary clinical
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Aims and objectives of the neuropathic pain
pathway
The neuropathic pain pathway was developed in response to
the need highlighted above, and with the intention of
maximum accessibility and reading ease. It aims to take the
non-specialist from the point of recognizing ‘possible’ neuropathic pain through an evidence-based series of management
options to the point at which the pain (a) is managed satisfactorily, (b) resolves, or (c) requires specialist secondary care assessment and intervention. There is also guidance on
treatments and management to be used within specialist settings, which though less specific than the guidance for nonspecialist management, will inform General practitioners
(GPs) and others involved in shared care, and guide specialist
practice. Important features include: (i) the use of a limited
set of first- and second-line drugs; (ii) the parallel use of nonpharmacological approaches, self-help, and highlighted information resources; (iii) need for early and frequent review at the
outset of treatment to ensure that maximum effective/tolerated treatment is given as quickly as possible; (iv) need for
early specialist secondary care referral in severe or uncertain
disease without awaiting the end of the pathway (but also
for the pathway to continue while the specialist assessment
is awaited); and (v) information on secondary care interventions, drugs used with specialist supervision, and multidisciplinary pain management.
The pathway has been developed in collaboration between
the Map of Medicine editorial team, representatives of the BPS
and independent reviewers. It is based on well-reputed secondary evidence, as selected in accordance with the Map of
Medicine’s editorial methodology for developing care pathways. Practice-based knowledge has been added by clinicians
nominated by the BPS and by independent reviewers identified
by the Map of Medicine editorial team. For the detailed editorial
methodology please see the Neuropathic Pain Pathway provenance certificate (see Appendix 1, Supplementary material).
Map of Medicine care pathways can be customized to reflect
local commissioning needs and practices to provide comprehensive, evidence-based local guidance and clinical decision
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Neuropathic pain
support at the point of care. This article is complementary to
the published pathway.
referral, and their discussions with patients beforehand and
afterwards.
Discussion and practice points
How do we define a non-specialist?
The neuropathic pain care pathway is shown in Figure 1.
Several discussion and practice points are discussed below.
Both the NICE guidance and this pathway are intended for use
by ‘non-specialists’. In this context, ‘specialist’ refers to a professional’s knowledge, experience and resources for managing
neuropathic pain. So, while most ‘non-specialist’ doctors will be
general practitioners, the pathway is also aimed at consultants
and others expert in their own special field (e.g. diabetes and
orthopaedics), who need to know how to manage a patient
with neuropathic pain, according to current standards. Professionals who manage neuropathic pain all the time, already
working according to international standards, can deviate
from the pathway according to their specialist knowledge.
They are also likely to be those furnishing the details of the
final parts of the pathway, including supervising specific medications, coordinating multi-disciplinary interventions and
providing surgical treatments.
Comparison with National Institute of Health and
Clinical Excellence guidance (for details see: www.nice
.org.uk/CG96)
The pathway is similar in many ways, up to the point of specialist secondary care referral, to recent guidance produced in the
UK by National Institute of Health and Clinical Excellence
(NICE) for the pharmacological management in non-specialist
settings (currently under review).22 NICE guidelines set
evidence-based standards for healthcare, focus on costs and
benefits, and are adopted as the standard for practice in the
NHS in England. However, this pathway is broader than the
NICE guidance, aiming to provide an overview of all relevant
management approaches, in a format that can be used in
other healthcare settings, while still retaining the basis in
current evidence. With respect to recommended pharmacological treatment, important differences from NICE include
this pathway’s recommendation of gabapentin, a range of tricyclic antidepressants or carbamazepine among drugs in firstline treatment (NICE recommends pregabalin or amitriptyline,
or duloxetine specifically in painful diabetic neuropathy).
Topical treatment (e.g. capsaicin 0.075% cream) for localized
areas of neuropathic pain is included in this pathway, but not
in the NICE guidance. These treatments are simple and
logical, even though evidence for their effectiveness is less
robust than for oral medications.22 NICE specifies that strong
opioids should only be prescribed in collaboration with specialist care; this pathway includes strong opioids in thirdline treatment, but highlights the importance of competence
and experience in their use, and suggests adherence to
the BPS’s guidelines.23 The pathway also considers nonpharmacological approaches, and includes recommendations
for patient information resources and team approaches including links to other pathways. It is important that much of the evidence for non-pharmacological treatment is not specific to
neuropathic pain. We need to be speculative in extrapolating
evidence from non-specific studies to neuropathic pain, but
consensus and clinical experience provide good reason to
believe that the recommendations in this pathway will be
helpful nonetheless, pending the necessary research.24 Some
are based on evidence assimilated in other NICE guidelines.25
26
Finally, this pathway includes some treatments that may
be more relevant outside some primary care settings. There
is now good evidence for the effectiveness of the capsaicin
8% patch (in post-herpetic neuralgia),27 but this still requires
specialist supervision.28 Other drugs such as lidocaine, or
those requiring local injection, are probably for the specialist
arena only, as, are surgical techniques or implants. It is
helpful for non-specialists to know about the existence and
the use of these approaches, both to inform the timing of
Initial assessment
Some helpful practical advice about the clinical presentation
and the diagnosis of neuropathic pain is provided. As highlighted above, this will alert the physician to the presence of
possible neuropathic pain. A brief but careful history and examination is the key to this diagnosis, along with an awareness of
the need to consider neuropathic mechanisms in anyone presenting with pain. Simple screening tools, such as the Leeds
Assessment of Neuropathic Symptoms and Signs (LANSS)
and PainDETECT,29 are available to assist in diagnosis, but are
not considered a substitute for these basic clinical skills, and
their positive predictive value in the primary care setting is
unknown.18 These questionnaire instruments share elements
in common with the advice provided in the pathway. Questions
about altered sensation and numbness in the area of pain,
evoked, or spontaneous pain sensations of unpleasant character (e.g. ‘shooting’ or ‘burning’ pains) are important. Similarly,
the demonstration of absent or altered sensation in the relevant area, in response to pinprick, vibration, hot, or cold pressure, or simple touch is important. The extent to which a
practitioner will be able to test these will depend on the
context in which he/she is working, but minimal testing
should always be possible, allowing the decision on whether
to embark on the pathway.
Reviewing progress
An important point that recurs in the pathway (and NICE guidance) is recommendations for the interval between reviewing
changes in medication. These are important in determining
when to move from first- to second- then third-line treatment.
A maximum review period of 2 weeks after initiating any treatment is specified. This allows: (i) the assessment of any effectiveness of the new treatment in improving symptoms; (ii) the
titration of dose as required; and (iii) the assessment of any
adverse reactions and the response to these. In most cases,
the starting dose will be lower than the maximum tolerated
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Key
More information
Care map
information
Information resources
for patients and carers
Referral
National info
Local info
Notes
Updates to this care
map
Pharmacological
information
Possible neuropathic
pain – clinical
presentation
Primary care
Secondary care
History and examination
Red flag and 4D risk
assessment
If criteria are met, refer
urgently to specialist
Explain condition and
provide information
and self-help options
Develop and agree a
management plan with
the patient including
ongoing assessment
Complex regional pain
syndrome (CRPS)
Go to complex
regional pain syndrome
First-line treatment
Topical treatment for
focal neuropathies
Second-line treatment
Add in tramadol as
third-line treatment
Review if not improved,
and consider referral
for further specialized
diagnostic testing
Refer for specialized
diagnostic testing
Confirm diagnosis and
consider
multi-disciplinary team
(MDT) referral
Develop and agree a
management plan with
patient including
ongoing assessment
Consider interventional
pain therapies and
medications that
require specialized
supervision
Provide a
multi-disciplinary
review to consider
treatment options
Fig 1 The neuropathic pain care pathway
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Neuropathic pain
effective dose, and this early review will optimize the interval to
achieve this, thereby minimizing suffering. Another important
timing point is that at which specialist referral (if required)
is made. In summary, this should be immediate if the pain is
severe, causing significant distress, if any ‘red flag’ factors are
present, or if diagnosis is difficult. Crucially, treatment should
continue, according to the pathway, while specialist review is
awaited. Otherwise, specialist referral should be made after
third-line treatment is proved unsatisfactory, if diagnostic uncertainty remains, or both, with a maximum of 6 months as
the initiation of first-line treatment. Again, treatment should
continue, for example, with the introduction of strong opioids
in accordance with BPS guidelines23 and according to the physician’s experience and skills. These approaches are intended
to reduce the occurrence of refractory neuropathic pain,
which is associated with particular suffering, disability, and
healthcare use.11
Complex regional pain syndrome
Complex regional pain syndrome (CRPS) is a chronic condition
that is notoriously difficult to treat successfully. Formerly
known as reflex sympathetic dystrophy or causalgia, it manifests as pain, swelling, and skin changes, and is associated
with a complex cluster of physical, emotional, and social problems. Our understanding of CRPS has been growing at a rapid
rate with a greater knowledge of the neural pathways involved
and the treatments that are likely to be successful, which were
summarized in a recently published set of guidelines.30 Previously, CRPS was thought of as a specific type of neuropathic
pain, but it is now generally considered to be a distinct clinical
entity. However, there are overlaps with neuropathic pain in
some of the pathophysiological and presenting features and
in the agreed approach to its management. The care
pathway group, therefore, chose to ‘signpost’ this important
topic as it may respond well to early management consistent
with the pathway.
Topical treatments
The pathway recommends use of topical treatments for localized causes of neuropathic pain, such as post-herpetic neuralgia, perhaps even before first-line treatment is given. This is at
odds with the NICE guidance, which concluded that: (i) there
was insufficient evidence to support the general use of weak
topical agents, such as capsaicin 0.075% cream or lidocaine
patches; and (ii) capsaicin 8% patches (for which the evidence
is stronger) are currently intended for specialist use.28 They are
included in this with the principle that ‘no absence of effectiveness is not equivalent to evidence of ineffectiveness’. Systemic
agents cause significant side-effects and drop-out from treatment is therefore common. There is good clinical consensus
that topical agents are effective in certain circumstances,
they may prevent the need for systemic therapies and contingent adverse reactions and interactions, and there was strong
patient-representative preference expressed for their use
during the development of the pathway. Finnerup and colleagues31 recommended the use of topical therapies for focal,
peripheral neuropathic pain, based upon the relative balance
between Number Needed to Treat and Number Needed to
Harm. They are not useful for widespread neuropathic pain,
and systemic therapy should be added or substituted quickly
in the event of non-response.
Gabapentin as first choice
This pathway recommends gabapentin among the choice of
first-line drugs. There was controversy with the publication of
the NICE guidance on the recommendation of pregabalin in
preference to gabapentin in first-line treatment of neuropathic
pain. Gabapentin is probably cheaper to supply and possibly of
equivalent efficacy. However, the conclusion reached by NICE,
based on their review of economic evidence, was that pregabalin was more cost effective, because of simpler administration
and titration regimes, and the lower incidence of adverse
effects, leading to fewer healthcare attendances.22 However,
as noted above, these findings are now being reviewed.
There is growing concern about the development of gabapentin and pregabalin as drugs of abuse, with exponential increase noted in rates of its prescription and relatively high
rates of use by attenders at substance misuse services.32
There are no controls on the prescribing of gabapentin, over
and above those for other prescription only medicines, and
physicians need to be aware of this potential for harm in addition to those listed in the standard drug information.
Carbamezapine
The pathway makes a clear recommendation for using carbamazepine as first-line therapy in the case of trigeminal neuralgia. The studies of carbamazepine’s efficacy date back to the
1960s and are well summarized in the American Academy of
Neurology’s guidelines on the management of this condition.33
There are some subsequent comparison studies described in
this guideline and subsequently,34 but the studies have small
numbers of recruits. The NICE neuropathic pain guidelines
made several suggestions for further research in this area to
confirm the clinical suspicion that carbamazepine holds its
place as first-line therapy. Until this has been done, there is
little argument to make any change from current recommendations.
Strong opioids
The use of strong opioids in chronic non-malignant pain, including neuropathic pain, is controversial, but their judicious
use is recommended in later parts of this pathway. Before prescribing strong opioids, the prescriber should screen for risk of
an addiction disorder, either based upon the history or using
a standard screening tool. Additionally, evidence is emerging
from US studies of the importance of maintaining a ceiling
morphine equivalent dose of no more than 120 mg in adults
and 50 mg in the elderly, and prescribing modified release
preparations only.35 36
There is reasonable evidence for the effectiveness of strong
opioids in the short- and medium-term, and though long-term
effectiveness remains incompletely assessed, there is good
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consensus that this is likely.23 However, what is unequivocal is
their potential for harm, including sedation, constipation,
hyperalgesia, reduced immunity, hormone suppression, and
dependence.22 35 36 Therefore, their use should be restricted
to refractory cases and to supervision by physicians experienced in their use and the assessment of the associated risks
and outcomes. Excellent guidance on this is available, as a consensus between the BPS and the Royal Colleges of Anaesthetists, General Practitioners, and Psychiatrists.23 Key to this is
detailed discussion with patients at the outset of treatment,
including agreed treatment goals, and knowledge of equivalent doses between different opioids.
Adopting a multi-disciplinary approach
The pathway has emphasized the importance of the interdisciplinary and multi-specialty approach in secondary care and
beyond; also, that there should be an agreed management
plan with the patient and shared care as appropriate. NICE
guidelines for neuromodulation and pain (Spinal Cord Stimulation and Deep Brain Stimulation) are available and are noted in
the specialist part of the pathway.25 26
The pathway has not attempted to cover in depth the treatments that should be considered in specialist secondary care
and beyond because this working group considered the focus
of the BPS care pathways to be non-specialist care. The evidence to support these approaches is growing and, in future
versions of the pathway, it may become appropriate to separate these treatments out from the others provided in specialist
care. The use of neurostimulation should be considered with
caution as the evidence for efficacy was based upon relatively
short-term studies, with some longer-term cohort studies suggesting a diminution of effect.37 Complex combinations of
analgesics need careful supervision because of the potential
for adverse effects and interactions.38 There is a relative
paucity of evaluation of standard psychological interventions
specifically for neuropathic pain, and therefore they are recommended largely to address the impact of pain.39 Neuropathic
radicular pain is considered in the low back pain pathway3 published in this issue of the BJA.
Conclusions
This pathway provides a useful approach to the management
of neuropathic pain by non-specialists, and indicates approaches that may be used in specialist secondary care. With
a basis in existing sources of best evidence and consensus, it
gives the opportunity for confidence in addressing this challenging and unpleasant clinical condition, while also paying attention to the co-morbidities that often accompany it. The
keys to its successful implementation, at the individual level,
are attention to the patient’s specific needs, early review of
the response to any treatment and referral for specialist assessment when it is clear that treatment is not working. In
this way, combining professional healthcare skills with the
pathway outlined here, the burden of neuropathic pain on
our patients can be reduced.
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Smith et al.
Supplementary material
Supplementary material is available at British Journal of Anaesthesia online.
Acknowledgements
The authors of this paper wish to acknowledge the following in
the production of the British Pain Society Neuropathic Pain
Patient Pathway: Map of Medicinew – The Neuropathic Pain
Care Map which can be found at www.mapofmedicine.com,
and of which an extract is included in this article, is published
with the authorization of Map of Medicine Limited who owns
the copyright; British Pain Society Pain Patient Pathway Maps
Executive Committee: Andrew Baranowski (Chair), Martin
Johnson, Richard Langford, Cathy Price; British Pain Society
Neuropathic Pain Patient Pathway Map working group (in
addition to authors): Dave Bennett, Sam Chong, Andrew Rice,
Mick Serpell, Heather Wallace.
Declaration of interest
All authors contributed to the design and writing of this paper,
without any financial or other assistance. B.H.S. was a
co-investigator in neuropathic pain epidemiology research
funded by Pfizer (unrestricted educational grant) Consultancy:
Pfizer; Treasurer of Neuropathic Pain Special Interest Group,
International Association for the Study of Pain; Director, Scottish Pain Research Community. J.L. is a member of the
medical charity SPIN (Specialists in Pain International
Network). C.P. Meeting travel: Napp; executive member of
Chronic Pain Policy Coalition; executive member of the BPS
Pain Patient Pathway Maps Executive Committee and
member of its Implementation Committee; a member of the
medical charity SPIN. A.P.B. is Chair of the NHSCB, Clinical Reference Group for Specialised Services—Pain, England; advisor
on Specialised Commissioning to various professional bodies;
Chair of Pain of Urogenital Origin Taxonomy Group, SIG of International Association for the IASP; member of European Association of Urology, Chronic Pelvic Pain working group; executive
member (Honorary Treasurer Elect) of British Pain Society;
Chair of the BPS Pain Patient Pathway Maps Executive Committee and member of its implementation Committee; Chair of the
Scientific Committee, 1st World Congress on Abdominal and
Pelvic Pain; member of the medical charity SPIN; and Consultant on research for Mundipharma.
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