Cancer and Neuropathic Pain

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Cancer and Neuropathic Pain

• Mike Bennett
• Professor of Palliative Medicine
• Lancaster University

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Case history

• 52 year old man
• Six month history of colon cancer
• Recent progression on chemotherapy
• liver and lung metastases

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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

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Hb 9.4 WCC 4 (1.2 neut) Plat 117
Barthel score 72 / 100 Pain helped initially
by codeine, but pain now more intense
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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?

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Neuropathic painDefinitions

• 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.

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Neuropathic painKey features

• Symptoms
• Spontaneous pains (pain without stimulation)
• Continuous dysaethesias burning, tingling
• Paroxysmal shooting, electric shocks
• Evoked pains
• hypersensitive skin cant bear to be touched

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Neuropathic painKey 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

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Mechanisms

• Peripheral
• nociceptor sensitization
• abnormal axonal responses
• Central
• disinhibition
• hyperexcitability

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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

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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

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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

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Epidemiology

• Aetiology
• direct effects of cancer
• indirect effects of cancer
• cancer treatment
• co-morbid conditions

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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

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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

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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

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• 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

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AssessmentCurrent 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

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AssessmentCurrent 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

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Common Features of Screening Tools
LANSS NPQ DN4 Pain Detect ID Pain
Symptoms
Pricking, tingling, pins, and needles
Electric shocks or shooting
Hot or burning
Numbness
Pain evoked by light touching
Painful cold or freezing pain
Clinical examination
Brush allodynia
Raised soft touch threshold -
Raised pinprick threshold
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Clinician Certainty Ratings of Presence of
Neuropathic Pain
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SD 35.6Mean 48.9N 200
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0
0
10
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30
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50
60
70
80
90
100
Clinician VAS Score
Bennett et al. Pain. 2006122289-94.
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Certainty of clinician ratings, S-LANSS score,
and composite NPS score (median, IQR)
Unlikely NeuP(n 67) Possible NeuP(n 67) Definite NeuP(n 66) P value
Clinician rating 7 (3,13) 50 (32, 65) 88 (84, 94) lt 0.001
S-LANSS 3 (0, 8) 13 (6, 20) 19 (12, 23) lt 0.001
NPS 41 (32, 54) 53 (40, 65) 57 (48, 69) lt 0.001
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Assessment

• Neuropathic pain mechanisms / symptoms exist as a
  spectrum
• More useful concept (esp in cancer pain)
• Pain of predominantly neuropathic origin

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Management

• Diagnose pain
• Use multimodal approach
• Conventional drugs and routes help but
  alternatives are often necessary
• this means opioids plus co-analgesics

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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

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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

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ManagementNNT 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)
• Dont forget NNH

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BMJ 15 August 2009, Volume 339
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ManagementNNT 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)

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A pragmatic approach

• A. Initial steps
• 3. GABAPENTIN
• add in or replace
• 2. AMITRIPTYLINE
• add in or replace
• 1. WHO LADDER

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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

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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

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• When to contact palliative care
• Opioid switching, esp methadone
• Ketamine
• Inpatient admission for
• clinical assessment by specialist team
• managing distress
• family support

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• When palliative care teams contact pain teams
• intercostal blocks
• paravertebral blocks
• spinal opioid infusions

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• When pain teams contact neurosurgeons
• Cordotomy

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SummaryNeuropathic 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 co-analgesics, but sometimes need specialist
  help

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• Thank you
• m.i.bennett_at_lancaster.ac.uk