Cancer and Neuropathic Pain

Mike BennettProfessor 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

WCC = 4 (1.2 neut)

Plat = 117

Barthel score = 72 / 100

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 1999Grond 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 CancerBecker 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 sensationGlynn Pall Med 1989

– Positive and negative phenomenaOchoa 1987

– LANSS Pain ScaleBennett 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 PainDetect

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 * – * – –

Clinician Certainty Ratings of Presence of Neuropathic Pain

0

10

20

0 10 20 30 40 50 60 70 80 90 100

Clinician VAS Score

SD = 35.6Mean = 48.9N = 200

Bennett et al. Pain. 2006;122:289-94.

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) < 0.001

S-LANSS 3 (0, 8) 13 (6, 20) 19 (12, 23) < 0.001

NPS 41 (32, 54) 53 (40, 65) 57 (48, 69) < 0.001

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 28mmGrond 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 steps3. 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 co-analgesics, but sometimes need specialist help

Thank you

m.i.bennett@lancaster.ac.uk