Transcript Neuropathic Pain

NEUROPATHIC PAIN
Summary
 Neuropathic pain – Nerve injury / compression
 Comprehensive assessment helps dignosis
 Multiple mechanisms
 Follow step ladder for drug treatment
 Treat Total Pain
Neuropathic Pain
Definition:
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 Pain
 Nerve Compression
 Nerve Injury
Central
Peripheral
Sympathetic
Eg. Post-stroke pain
Spinal Cord Compression
Visceral
Plexopathies
Somatic
peripheral neuropathy
eg. post-herpetic neuralgia
Common Neuropathic Pain Situations
 Amputation - eg. Phantom limb pain
 Back, leg, and hip problems (Sciatica)
 CANCER and its treatment
 Diabetes
 Trigeminal neuralgia
 HIV infected or AIDS
 Herpes zoster virus infection
 Complex Regional Pain Syndromes
 Cerebro-Vascular Accident
Causes of Neuropathic pain
in advanced Cancer
Cancer
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Nerve compression / infiltration
Plexopathy
Spinal cord compression
Thalamic tumour
Debility
• Postherpetic neuralgia
Anticancer treatment
 Chronic surgical incision pain
 Phantom limb pain
 Chemotherapy- peripheral
neuropathy
 Radiation fibrosis - Plexopathy,
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 pain
Distribution:
 If peripheral nerve injury - neurodermatomal
 If 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 abnormalities
 Motor and trophic changes - thinning of skin
What Does Patient Complain of ?
 Burning
 Numbness
 Paroxysmal
 Lancinating
 Shooting
 Raw Skin Feeling
 “ants crawling”
 “bag of worms”
Nerve
injury
NMDA and Glutamate
mechanisms
Dorsal horn
Neuropathic Pain
Hyperexcitability
and spontaneous
activity
Central sensitization
Serotonin,
noradrenaline
Chemical Excitation of Non-nociceptors
beta
Mechanisms of Neuropathic Pain
1.
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
Central Sensitisation - Role of NMDA Receptor
• Present mainly in Dorsal Horn Cells
• Increased Stimulation causes ‘Wind up’ Phenomena
• Increased Excitation leads to Persisting pain
Agents which increase NMDA Receptor activity:
Glutamate
Substance P
Excessive Sodium channels
Excessive Calcium channels
Decreased Potassium channels
Nerve Growth Factor, Nitric-oxide
NERVE INJURY
DRUG
NEUROCHEMICAL
ANATOMICAL
 INCREASE IN SURVIVAL FACTORS
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CELL DEATH
ALTERATION OF TROPHIC FACTOR EXPRESION
SYMPATHETIC
SWITCH IN EXITATORY PEPTIDES
SPROUTING
INCREASE OF INHIBITORY PEPTIDES
CHANGE IN RECEPTOR EXPRESSION
INCREASE IN NITRIC OXIDE SYNTHASES
CHANGE IN ION CHANNEL
ALL THE ABOVE LEADS TO PHYSIOLIGICAL CHANGES LIKE
REDUCTION IN PRESYNASPTIC INHIBITION
ECTOPIC DISCHARGES
NERVE INJURY
DORSAL HORN
NEUROCHEMICAL
REDUCTION IN GABA AND GABA RECEPTORS
REDUCTION IN OPIOD RECEPTORS
GLIA CELL ACTIVATION
INCREASE IN CYTOKINES
INCREASE IN IMMEDIATE EARLY GENES
INCREASE IN TRANSCRIPTION SIGNALS
ANATOMICAL
TERMINAL ATROPHY
CELL LOSS
APOPTOSIS
ALL THESE ABOVE CHANGES CAUSES
INCREASED WINDUP, LONG TERM POTENTIATION
REDUCED INHIBITORY CONTROLE IN DORSAL HORNS
Recruitment
Nerve injury + recruitment of nerves outside site of injury
State of Hyperalgesia - Primary and secondary
Neuroanatomical
Reorganisation
Recruitment to
adjacent
segments
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 EXCITABILITY
 VOLTAGE 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
Sodium-channel
Anticonvulsants
Carbamazepine
Valproate
Gabapentin
Pregabalin
Clonazepam
blockade
Lidocaine
Opioids
NSAIDs
Activation of
GABA
inhibitory system
Baclofen
Enhanced
descending
Inhibition
Tricyclics
SSRIs
Alpha2adrenergic
agonists
Tramadol
Inhibition of
glutamate
excitatory
system
Mechanism-based therapy
Ketamine
Amantidine
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
Treatment of Neuropathic Pain
NMDA receptor
Coticosteroid
For Nerve
Compression
Tricyclic
antidepressant
or
anti-epileptic
Tricyclic
anti
-channel blocker
depressant
and
Step 4
anti-epileptic
Invasive
Techniques
Step 5
Step 3
Step 2
Step 1
Try Opioids first in cancer or severe non-cancer pain
Corticosteroid
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INFLAMMATORY NEUROPATHIC PAIN
BONE PAIN
PAIN FROM BOWEL OBSTRUCTION
PAIN FROM LYMPHOEDEMA
HEADACHE 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
T
Nerve
After Corticosteroid
T
Nerve
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 pain
 Action : Prevention of reuptake of serotonin& Norad
Alfa adrenergic blockade
Na channel effect,
NMDA antagnsm
 Start with 10 to 25 mg at night and increase every third day
up to 75 to 100 mg if necessary
 Side effects - sedation, constipation, urinary retention,
heart block aggravated
Other TCAs -
Step 2 / Step 3 - Anticonvulsants
 Preferred 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 effects
 Expensive
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 Antagonists
Oral Ketamine :
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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 Anaesthetics
 Action-
Blocking the Na channels
 Ex-Lidocaine,Mexilitine
Autonomic drugs
 Alfa2 Agonist-
Clonidine
 Alfa1 Antagonist- Prazocin,Terazocine
 Othrs like CAPSAICIN CREAM
Interventional Techniques
 Sympathetic 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 Injections
 Somatic Nerve Block
 Neurolytic block
 Epidural
What should be the aim of our treatment ?
To improve quality of life !
Non-Physical Components of Pain
Physical
Psychological
Total Pain
Spiritual
Social