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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
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
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