NEUROPATHIC PAIN. Summary Neuropathic pain – Nerve injury / compression Comprehensive assessment helps dignosis Multiple mechanisms Follow step ladder.

NEUROPATHIC PAIN

SummaryNeuropathic pain – Nerve injury / compression

Comprehensive assessment helps dignosis

Multiple mechanisms

Follow step ladder for drug treatment

Treat Total Pain

Neuropathic PainDefinition:International Association for the Study of Pain

defines Neuropathic pain as :

“ pain initiated or caused by primary lesion or dysfunction of the nervous system”

Also defined as ‘Pain in an area of absent sensation’

Classification of Neuropathic PainNerve Compression

Nerve Injury

Central Peripheral

Eg. Post-stroke pain Spinal Cord Compression

peripheral neuropathyeg. post-herpetic neuralgia

Visceral Somatic

Plexopathies

Sympathetic

Common Neuropathic Pain Situations

Amputation - eg. Phantom limb painBack, leg, and hip problems

(Sciatica)CANCER and its treatmentDiabetesTrigeminal neuralgiaHIV infected or AIDSHerpes zoster virus infection Complex Regional Pain SyndromesCerebro-Vascular Accident

Causes of Neuropathic pain in advanced Cancer

CancerNerve compression / infiltrationPlexopathySpinal cord compressionThalamic tumour

Anticancer treatmentChronic surgical incision painPhantom limb painChemotherapy- peripheral

neuropathyRadiation fibrosis - Plexopathy,

neuralgia

Debility

• Postherpetic neuralgia

Concurrent disorders

• Diabetic neuropathy

• Post-stroke pain

Hallmarks of Neuropathic Pain Allodynia : Pain resulting from a stimulus that normally

does not evoke pain. Thermal or mechanical stimuli Hyperalgesia : Something that is normally painful is now more

painful than usual Exaggerated response to a normally painful

stimulus Pain within area of injury - Primary

Hyperalgesia Pain in surrounding undamaged area -

Secondary Hyperalgesia

Clinical features of nerve painDistribution:If peripheral nerve injury - neurodermatomalIf central - larger area of abnormal sensation

If Sympathetic component is present

Pain felt in area of distribution of the vessel Vasomotor disturbances : redness, pallor,

swelling Sweating abnormalitiesMotor and trophic changes - thinning of skin

What Does Patient Complain of ?

BurningNumbnessParoxysmalLancinatingShootingRaw Skin Feeling“ants crawling”“bag of worms”

Neuropathic Pain Hyperexcitability

and spontaneous

activityCentral sensitization

Nerve injury

Dorsal horn

NMDA and Glutamate mechanisms

Serotonin,

noradrenaline

Chemical Excitation of Non-nociceptors

beta

Mechanisms of Neuropathic Pain1. Chemical Excitation of non-nociceptors

2. Recruitment of nerves outside the site of injury

3. Excitotoxicity

4. Excess Sodium channels

5. Ectopic discharge

6. De-afferentation

7. Central sensitization maintained by peripheral input

8. Sympathetic involvement

9. Ephaptic cross talk

Glutamate

Substance P

Excessive Sodium channels

Excessive Calcium channels

Decreased Potassium channels

Nerve Growth Factor, Nitric-oxide

• Present mainly in Dorsal Horn Cells

• Increased Stimulation causes ‘Wind up’ Phenomena

• Increased Excitation leads to Persisting pain

Agents which increase NMDA Receptor activity:

Central Sensitisation - Role of NMDA Receptor

NERVE INJURY

DRUG

NEUROCHEMICAL ANATOMICAL

INCREASE IN SURVIVAL FACTORS CELL DEATHALTERATION OF TROPHIC FACTOR EXPRESION

SYMPATHETIC SWITCH IN EXITATORY PEPTIDES

SPROUTING INCREASE OF INHIBITORY PEPTIDESCHANGE IN RECEPTOR EXPRESSION INCREASE IN NITRIC OXIDE SYNTHASESCHANGE IN ION CHANNEL ALL THE ABOVE LEADS TO PHYSIOLIGICAL CHANGES LIKE REDUCTION IN PRESYNASPTIC INHIBITION ECTOPIC DISCHARGES

NERVE INJURY

DORSAL HORNNEUROCHEMICAL

ANATOMICALREDUCTION IN GABA AND GABA RECEPTORS TERMINAL

ATROPHYREDUCTION IN OPIOD RECEPTORS CELL LOSSGLIA CELL ACTIVATION APOPTOSISINCREASE IN CYTOKINESINCREASE IN IMMEDIATE EARLY GENESINCREASE IN TRANSCRIPTION SIGNALS

ALL THESE ABOVE CHANGES CAUSES

INCREASED WINDUP, LONG TERM POTENTIATION

REDUCED INHIBITORY CONTROLE IN DORSAL HORNS

Recruitment

Neuroanatomical Reorganisation

Recruitment to adjacent segments

Nerve injury + recruitment of nerves outside site of injury

State of Hyperalgesia - Primary and secondary

Ectopic Discharge

Discharge of impulses from Areas

of nerve which

normally should not be discharging

1. Comprehensive Assessment

Look for clinical features :

Allodynia - pain on touch, cant bear a draft on skin, even clothes provoke hyperesthesia

Sensory deficit, numbness.

Hyperalgesia.

Occasional sympathetic component

Increased skin temperature, sweating

Patients exhausted, demoralised, sleepless.

ALTERED EXCITABILITYVOLTAGE SENSITIVE NA+ CHANNELS HAVE BEEN SHOWN ACCUMALATE IN NEUROMA NERV ENDINGS & IN PATCHES OF DEMYELINATION

AXONAL NEURAL MEMBRANE UNDER MYELIN NORMALLY CONTAINS A VERY LOW DENSITY NA+ CHANNELS B’CAUSE MYELIN SUPPRESS THEIR

INSERTION

DEMYELINATION, SPROUTING, ENDBULB FORMATION REMOVE THIS SUPPRESSION PERMITTING EXCESS

CHANNEL INSERTION

OpioidsNSAIDs

Sodium-channel

blockade

Lidocaine

EnhanceddescendingInhibition

Tricyclics

SSRIs

Alpha2-adrenergic agonists

Tramadol

Activation of GABA

inhibitory system

Baclofen

Inhibition ofglutamateexcitatorysystemKetamineAmantidine

AnticonvulsantsAnticonvulsantsCarbamazepineValproateGabapentinPregabalinClonazepam

Mechanism-based therapy

2. Management of Neuropathic pain Explanation

Analgesics : specific for neuropathic pain

other drugs : Non-opioids & Opioids

Interruption of pain pathways.

Physical therapy : Heat or cold pads, TENS

Psychological and modification of way of life

Step 1

Step 2

Step 3

Step 4

Step 5

Coticosteroid

For Nerve Compression

Tricyclicantidepressantoranti-epileptic

Tricyclicanti depressantandanti-epileptic

NMDA -receptor

-channel blocker

Invasive Techniques

Treatment of Neuropathic Pain

Try Opioids first in cancer or severe non-cancer pain

Corticosteroid INFLAMMATORY NEUROPATHIC PAINBONE PAINPAIN FROM BOWEL OBSTRUCTIONPAIN FROM LYMPHOEDEMAHEADACHE WITH RAISED ICT

ACTION

Inhibits PG production—Decreses inflammation—Decreases cappilary permeability—reducing peritubular oedema

Membrane stabilization---Decreases Neuronal excitability

Dexamethasone – Oral or Injection

I.V. 8 - 24 mg/day for 3 days and continue with oral drug in diminishing dose

After Corticosteroid

Nerve

Nerve

T

T

Step 1 - Opioids

In Neuropathic pain related to

Cancer :More than one pain often present

Try opioids first

50% of pain may be reduced with opioids

helps reduce dose of specific neuropathic pain

drugs

Step 2 - TriCyclic Antidepressants

Amitryptiline :Particularly in burning type of painAction : Prevention of reuptake of serotonin&

Norad Alfa adrenergic blockade Na channel effect, NMDA antagnsmStart with 10 to 25 mg at night and increase

every third day up to 75 to 100 mg if necessarySide effects - sedation, constipation, urinary

retention, heart block aggravated Other TCAs -

Step 2 / Step 3 - AnticonvulsantsPreferred for shooting lancinating type of pain

Action : Suppress spontaneous neuronal discharges &

hyperexcitability

Depress the exitatory pathways,

Facilitates the inhibitory mechanisms

Drugs used: Carbamazepine , sodium valproate

Carbamazepine : 100 - 200mg/day increased every third day by 100 mg up to 400 - 800 mg/day Side effects : gastric irritation, sedation, giddiness, ataxia, confusion

Anticonvulsants

GABAPENTIN &PREGABALIN

ACTION- Act on neither GABA nor Na channels Modulate the cellular Ca influx into nociceptive neurons by binding to vlotage gated Ca channels

preferred in Post Herpetic Neuralgia & Diabetic neuropathy less side effectsExpensive

Dose of Gabapentin: Start with 200 to 300 mg/day , increase up to 1200 to 1800 mg/ day in divided doses. Dose of Pregabalin : Start with 75 mg 12Qh, increase by adding 75mg every 3 to 4 days, upto 300 mg Q12h

NMDA Receptor AntagonistsOral Ketamine :

Injectable form: given mixed in sweetened beverage

Starting dose : 0.25 to 0.5 mg/kg (approximately 25mg /adult dose)

4 - 6 hourly - gradually increased

Side effects : delirium, hallucinations, nightmares

Systemic Local AnaestheticsAction- Blocking the Na channelsEx-Lidocaine,Mexilitine

Autonomic drugsAlfa2 Agonist- ClonidineAlfa1 Antagonist- Prazocin,Terazocine

Othrs like CAPSAICIN CREAM

Interventional TechniquesSympathetic Blockade

eg. Lumbar Sympathetic block

for pelvic or lower limb pain (e.g. Ca cervix)

Stellate Ganglion block for upper limb pain as in Ca Breast

Trigger Point InjectionsSomatic Nerve Block Neurolytic blockEpidural

What should be the aim of our treatment ?

To improve quality of life !

Total Pain

Physical

Spiritual

Psychological Social

Non-Physical Components of Pain