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Cancer and
Neuropathic Pain
Mike Bennett
Professor of Palliative Medicine
Lancaster University
Case history
• 52 year old man
• Six month history of colon cancer
• Recent progression on chemotherapy
– liver and lung metastases
Case history
• Presents to your clinic with mass in left chest
wall
– constant aching pains in chest
• occasional paroxysmal pain radiating around chest
– dysaesthesias over left chest wall
– non-tender mass but dynamic mechanical
allodynia in T7-8 dermatomes
Hb = 9.4
Barthel score = 72 / 100
WCC = 4 (1.2 neut)
Plat = 117
Pain helped initially by codeine, but pain
now more intense
TASK
• What is your pain diagnosis?
– any other information needed
• What other investigations or assessments would you
request?
• What is your management plan?
• What is your main outcome measure of success?
Neuropathic pain
Definitions
• Neuropathic pain
– Pain arising as a direct consequence of a lesion
or disease affecting the somatosensory system
– = abnormal activation of pain pathways
• Nociceptive pain
– inflammatory pain
– normal activation of pain pathways.
Neuropathic pain
Key features
• Symptoms
– Spontaneous pains (pain without stimulation)
• Continuous = dysaethesias; burning, tingling
• Paroxysmal = shooting, electric shocks
– Evoked pains
• ‘hypersensitive skin’; can’t bear to be touched
Neuropathic pain
Key features
• Signs
– Abnormal response to stimulation
• Allodynia = pain after non-noxious stimulus
• Hyperalgesia = exaggerated pain after noxious stimulus
• Hyperpathia = temporal and spatial abnormalities
– Loss of sensation
– Autonomic changes
• Mottled, flushed, sweating
Mechanisms
• Peripheral
– nociceptor sensitization
– abnormal axonal responses
• Central
– disinhibition
– hyperexcitability
Neuropathic pain in cancer
- the issues
• Epidemiology
• Assessment
– is it different to NeuP in non-cancer patients?
– how to recognise it
– patient related factors
• Management principles
Epidemiology
• Neuropathic pain probably affects 40% of
patients with cancer pain
– vast majority have mixed mechanism pain
• …and is associated with greater pain
intensity
Caraceni and Portenoy Pain 1999
Grond et al Pain 1999
Epidemiology
• Compared with nociceptive pain:
– less pain relief with single doses of opioids
– more likely to escalate opioid doses
– likely to have poorer outcome with treatment
– ….even spinal analgesia is less effective
Cherny et al Neurology 1994
Vigano et al Cancer 1998
Mercadante et al 2000 Supp Care Cancer
Becker et al 2000 Stereo Funct Neurosurg
Epidemiology
• Aetiology
– direct effects of cancer
– indirect effects of cancer
– cancer treatment
– co-morbid conditions
Assessment
• Clinically
– pains are often mixed, evolving quickly
• Pathologically
– similar peripheral and spinal mechanisms as in non-cancer
patients
• Pharmacologically
– frail patients; cognitive, hepatic and renal impairment
• Psychologically
– preparing for prognosis of weeks to months
Assessment
• Patterns of pain are varied
– slowly evolving over weeks
– acute on chronic exacerbation over days
– sudden onset
• Screen for cognitive, hepatic and renal
impairment
Assessment
• Are neuropathic mechanisms present?
– Pain in an area of altered sensation
Glynn Pall Med 1989
– Positive and negative phenomena
Ochoa 1987
– LANSS Pain Scale
Bennett Pain 2001
– S-LANSS (self report LANSS)
Bennett et al J Pain 2005
• Diagnosis is clinically
based
• Screening tools exist
– LANSS pain scale
• 7 item tool
– 5 questions, 2
examination items
• Validated
– worldwide
– in variety of chronic
pain states
Assessment
Current screening tools
• Content
– short lists of classic descriptors or symptoms
– some have brief clinical examination
• Usually physician administered
– but several patient self-report versions
• Easy to complete
– total score suggests presence or absence of
neuropathic pain mechanisms
Assessment
Current screening tools
• LANSS and S-LANSS
– Bennett, Pain 2001
– Bennett et al, J Pain 2005
• Neuropathic Pain Questionnaire (NPQ)
– Krause, Backonja, Clin J Pain 2003
• DN4
– Bouhassira et al, Pain 2005
• ID Pain
– Portenoy, Curr Med Res Opin 2006
• PainDetect
– Freynhagen et al , Curr Med Res Opin 2006
Common Features of Screening Tools
LANSS
NPQ
DN4
Pain
Detect
ID Pain
Pricking, tingling, pins, and
needles
*
*
*
*
*
Electric shocks or shooting
*
*
*
*
*
Hot or burning
*
*
*
*
*
*
*
*
*
*
*
Symptoms
Numbness
Pain evoked by light touching
*
Painful cold or freezing pain
*
*
*
–
*
–
–
–
*
–
-
–
*
–
–
Clinical examination
Brush allodynia
*
Raised soft touch threshold
Raised pinprick threshold
*
Clinician Certainty Ratings of
Presence of Neuropathic Pain
20
SD = 35.6
Mean = 48.9
N = 200
10
0
Clinician VAS Score
Bennett et al. Pain. 2006;122:289-94.
Certainty of clinician ratings, S-LANSS score,
and composite NPS score (median, IQR)
“Unlikely “Possible “Definite
P
NeuP”
NeuP”
NeuP”
value*
(n = 67)
(n = 67) (n = 66)
Clinician
rating
7 (3,13)
50 (32, 65)
88 (84, 94) < 0.001
S-LANSS
3 (0, 8)
13 (6, 20)
19 (12, 23) < 0.001
41 (32, 54)
53 (40, 65)
57 (48, 69) < 0.001
NPS
Assessment
• Neuropathic pain mechanisms / symptoms
exist as a spectrum
• More useful concept (esp in cancer pain)
– ‘Pain of predominantly neuropathic origin’
Management
• Diagnose pain
• Use multimodal approach
• Conventional drugs and routes help but
alternatives are often necessary
–
this means opioids plus co-analgesics
Management
Neuropathic pain and cancer
• The difference is in the patient not the pain
– more frail
– changing pain picture
– additional renal, hepatic or cognitive impairment
• Toxicity may be reached before benefit
– NNT may be higher
– NNH may be lower
Management
• 593 cancer pain patients treated with WHO
guidelines (opioids +/- co-analgesia)
– NeuP no more intense than nociceptive group
• 96% had opioids
• 53% had adjuvants (sig more than nocicept group)
– VAS decreased from 70mm to 28mm
Grond et al Pain 1999
Management
NNT and evidence based ladders
• Note that ‘50% pain relief’ can mean:
– 50% reduction in VAS where measured
– ‘excellent or good’ relief
– but also ‘moderate’ relief
• Confidence intervals of NNTs important too
– SSRIs 6.7 (3.4 - 435)
• Don’t forget NNH
BMJ 15 August 2009, Volume 339
Management
NNT and evidence based ladders
• WHO ladder
– morphine 2.5
– oxycodone 2.6
• Tricyclics
– amitriptyline group 2.0, NNH 3.7
• Antiepileptics
– gabapentin NNT 3.5, NNH 2.5
– or carbamazepine better? (NNT 2.3, NNH 3.7)
A pragmatic approach
A. Initial steps
3. GABAPENTIN
[add in or replace]
2. AMITRIPTYLINE
[add in or replace]
1. WHO LADDER
A pragmatic approach
B. Advanced steps ‘The unlit loft at the top of the ladder’
6. METHADONE [or
other opioid switch]
5. ANAESTHETIC
APPROACHES
4. KETAMINE [with opioid]
Treatment
• What you can do…….
– WHO ladder works for many patients
• no opioid is superior to another, just different
– Add in co-analgesics
• Antidepressants = amitriptyline, duloxetine
• Antiepileptics = gabapentin, pregabalin
• When to contact palliative care
– Opioid switching, esp methadone
– Ketamine
– Inpatient admission for
• clinical assessment by specialist team
• managing distress
• family support
• When palliative care teams contact pain
teams
– intercostal blocks
– paravertebral blocks
– spinal opioid infusions
• When pain teams contact neurosurgeons
– Cordotomy
Summary
Neuropathic mechanisms in cancer pain:
– are common
– often present as a spectrum with nociceptive
mechanisms
– are caused by cancer and its treatment
– are sometimes accompanied by cognitive, hepatic and
renal impairment
– can usually be effectively treated with opioids and coanalgesics, but sometimes need specialist help
Thank you
[email protected]