This document provides an overview of neuropathic pain, including its definition, symptoms, causes, assessment, and treatment. Some key points: - Neuropathic pain is caused by damage or disease affecting the somatosensory nervous system. It is described as burning, shock-like, or tingling. - It has both positive symptoms like allodynia and dysasthesia, and negative symptoms like hypoalgesia. Common causes include shingles, diabetes, spinal cord injury. - Assessment involves screening tools, neurophysiological tests, and sometimes nerve biopsies. Treatment includes antidepressants like amitriptyline, anticonvulsants like gabapentin and pregabalin, opioids

1. NEUROPATHIC PAIN
Causes,Management ,and
Understanding
Edited by,
Cory Toth MD
Dwilight E.Moulin MD

2. DEFINITION:
• In 1994, the International Association for the Study of Pain (IASP)
defined neuropathic pain as “pain initiated or caused by a primary lesion or
dysfunction in the nervous system.”
• In 2008,the definition was revised by NeuPSIG of IASP,to be “pain arising as a
direct consequence of a lesion or disease affecting the somatosensory system”
How it is Different from Nociceptive pain?
-Confined to innervation territory of the lesioned nervous structure.
-Patient describe it as burning/electric shock-like/pin & needle/numb/tingling
sensation.
-Poor response to analgesics.

3. POSITIVE SENSORY SYMPTOMS:
• Allodynia-Pain caused by a normally non-painful stimulus.
• Anesthesia Dolorasa-Pain in the area which is anesthetic.
• Hyperalgesia-A heightened experience of pain caused by a stimulus which is
normally painful.
• Dysaesthesia-An unpleasant abnormal sensation,whether spontaneous or
evoked(shooting-like).
• Paraesthesia-An abnormal sensation that is not unpleasant(tingling,buzzing).
NEGATIVE SENSORY SYMPTOMS:
• Anesthesia-Total loss of sensation.
• Hypoalgesia-Diminished pain in response to a normally painful stimuli.
• Analgesia-Absence of pain in response to a painful stimuli.

4. EXAMPLES OF NEUROPATHIC PAIN SYNDROMES:
1. Peripheral Nervous System:
• Trigeminal neuralgia
• Post herpetic neuralgia(25-50%)
• Painful neuropathy(Diabetes,Alcohol)
• Phantom limb pain
2. Central Nervous System:
• Post stroke pain(8%)
• Multiple sclerosis(55%)
• Spinal cord injury (75%)
3. Mixed:
• Subgroups of patients with chronic back pain(55%)
• Subgroups of patients with cancer-related pain(33%)
• Complex regional pain syndrome

5. Normal pain circuitries involve activation of a nociceptor in response
to a painful stimulus. A wave of depolarization is sent to the first-order
neurons, with sodium rushing in via sodium channels and potassium
rushing out. First order neurons end in the dorsal horn of the spinal
cord. It is here that the electrochemical signal opens voltage-gated
calcium channels in the pre-synaptic terminal, allowing calcium to
come in. Calcium allows glutamate, an excitatory neurotransmitter, to
be released into the synaptic space. Glutamate binds to NMDA
receptors on the second-order neurons, causing depolarization.
These neurons then cross over in the spinal cord and go up to the
thalamus, where they synapse with third-order neurons. These, in
turn, connect to the limbic system and cerebral cortex. There is also
an inhibitory pathway that prevents pain signal transmission in the
dorsal horn. Anti-nociceptive neurons originate in the brain stem and
travel down the spinal cord where they synapse with short
interneurons in the dorsal horn by releasing serotonin and
norepinephrine. The interneurons modulate the synapse between the
first-order neuron and the second-order neuron by releasing(GABA),
an inhibitory neurotransmitter. Hence, pain cessation is the result of
inhibition of synapses between first and second order neurons, while
pain enhancement may be the result of suppression of inhibitory
synaptic connections.

7. HISTORY:
OPQRST approach:
• Onset
• Provocation
• Quality
• Region
• Severity
• Time duration
Pain Diagrams:
• Useful tool to rapidly & accurately localize source of chronis pain.
• Patients are instructed to colour /shade where they have pain,sometimes with simple word
descriptors.
Areas of further exploration:
• Past medical history
• Use of pain medications
• Exposure to infections
• Associated psychological disturbance

8. PAIN ASSESSMENT:
1. Screening Tools
• Leeds Assessment of Neuropathic Symptoms and Signs
• Douleur Neuropathique 4 questions
• Neuropathic Pain Questionnaire
• painDETECT
• ID Pain
2.Neurophysiology
 Nerve Conduction Studies
 Electromyography(EMG)
 Microneurography
 Laser evoked Potential(LEP)
3.Functional Neuroimaging
4.Nerve biopsy

9. TREATMENT:
Antidepressants:
• Both Tricyclic antidepressants and serotonin reuptake inhibitors are recommended
as the 1st line agents for neuropathic pain.
• Amitriptyline is the first line drug for post stroke pain and is also recommended for
pain due to spinal cord injury.However, TCAs failed to shoe efficacy for
chemotherapy.
• Dosing:10-25mg at bedtime.Titrated every 3-7 days.Max dose 25 -150mg
• Venlafaxine,duloxetine are first line for painful polyneuropathy.
• Dosing:Venlafaxine 75 mg/day.Titrated once in 2 weeks.max dose 225 mg /day.
• Duloxetine 30mg and 60mg are starting and maintainence dose respectively.Max
dose 120mg/day.
Gabapentinoids:
• Gabapentin and pregabalin reduces pain by reducing calcium influx into the neuron
and subsequent reduction of the neurotransmitter.
• Available in 100mg,300mg,400mg capsules,600mg & 800mg film-coated tabs.
• Max dose of Gabapentin 3600mg for DPN and 1800mg for PHN.
• Max dose of Pregabalin 600mg/day within a week.

10. Antiepileptics:
• Carbamazepine involves blockade of Na channels.Used inTGN.Started at 100mg ,titrated
to maintainence dose of 400-800mg/day.
• Oxcarbamazepine Initiated at 300mg/day ,titrated over 4 weeks.Max dose is 900mg BID
• Others-Lamotrigine,Topiramate,Phenytoin,Valproic acid are also used.
Opioids:
• Tramadol 200-600mg/day for 6 weeks –PHN,50-400mg/day PDN
• Morphine 70-300mg/day for weeks-Phantom limb pain.also used in peripheral
neuropathy.
• Others-Fentanyl,Tapentadol
Cannabinoids:
• Dronabinol 10-20 mg is given in multiple sclerosis,spinal cord
injury,Nabiximols(THC+Cannabidiol),Nabilone.
Peripheral nerve stimulation
Intrathecal drug delivery

11. THANKYOU