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Flashcards in PHAR: Neuropathic pain Deck (23):

Definition of neuropathic pain.

  • What two categories of neuropathic npain are there?

Pain initiated or caused by a primary lesion or disease of the somatosensory system.

  • Peripheral neuropathic pain.
    • Pain initiated or caused by a primary lesion or disease in the peripheral somatosensory system.
  • Central neuropathic pain.
    • Pain initiated or caused by a primary lesion or disease in the central somatosensory system.


  • What are the three different categories of pain?
    • Describe them.


  • Nociceptive pain.
    • Early warning alarm system.
    • Withdrawal reflex.
    • High-threshold pain.
  • Inflammatory.
    • Positive symptoms (pain).
    • Inflammatory cells: macrophages, mast cells, neutrophils, granulocytes.
    • Low-threshold pain.
  • Pathological.
    • Nothing is wrong with the periphery, something is wrong with the system.
    • Feels as if it is in the periphery.
    • + and - symptoms (pain + numbness).

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  • What are the two types of pathological pain?
  • What differentiates them?
  • Give an example of both.

  1. Neuropathic pain.
  2. Dysfunctional pain.
  • Neuropathic pain = + and - symptoms.
    • Diabetic neuropathy.
      • Symptoms = dyesthesia (stabbing + burning pain) + paresthesia (tingling + numbness).
  • Dysfunctional pain = only + symptoms.
    • Fibromyalgia.
      • Symptoms: whole body pain.
      • Treatment: pregabalin.

Note: COX inhibitors won't work on pathological pain.


Define allodynia.

  • Give an example.

Central pain sensitization (increased response of neurons) following normally non-painful, often repetitive, stimulation.

  • Patient compaining of blanket brushing their feet and causing pain.



Give an example of:

Peripheral neuropathies under the following categories:

  • Metabolic.
  • Toxic.
  • Post-infectious.

Post-traumatic (x5).

Others (x3).

  • Metabolic: diabetic. 
  • Toxic: alcohol, chemotherapy, others.
  • Postinfectious: PHN (postherpetic neuralgia), HIV, CMV.


Post-traumatic (x5).

  • Sciatica.
  • Postoperative.
  • Neuroma or nerve entrapment.
  • Phantom limb pain.
  • CRPS (Complex Regional Pain Syndrome [RSD]).


Others (x3).

  • Spinal cord injury.
  • Post-stroke pain.
  • MS.


NOTE: The longer the nerve, the further the damage spreads.



  • What is the mechanism of neuropathic pain?
  • What is common to both peripheral and central neuropathic pain?

  • Different mechanisms for different patients.
  • Membrane hyperexcitability.
    • Ectopic discharge (discharge where discharge shouldn't occur).
  • Peripheral and central sensitisation occurs in the respective types of pain.


Explain the mechanism of peripheral sensitisation.

  • Sodium channel is most important channel in the periphery.
    • REVISION: Voltage-gated sodium channels play an important role in action potentials. If enough channels open when there is a change in the cell's membrane potential, a small but significant number of Na+ ions will move into the cell down their electrochemical gradient, further depolarizing the cell.
  • Damage nerves → nerves closed by or damaged nerve itself will overexpress Na channels → membrane becomes unstable (AP fired unnecessarily).

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Describe central sensitisation.

  • Ca channels: central neurons hyperexcited.
  • Hyperalgesia - increased Ca2+ influx → more pain than expected of injury.

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  • Differentiate between hyperalgesia and allodynia.
  • Describe the mismatch between stimulus and response process leading to allodynia.

  • Hyperalgesia = exaggerated reaction to normally painful stimulus.
    • Allodynia = pain response to sensation that shouldn't cause pain.
  • Second order neurons are hyperactive → cross talk between nerve fibres → touch activates second order nerons → touch is painful. 
    • Eg can't wear a shirt without it hurting.

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  • What are glia?
  • What role do they play in central sensitisation?

  • Non-neuronal cells.
    • Maintain homeostasis.
    • provide support and protection for neurons in the central and peripheral nervous systems.
    • "Skeleton" of the nervous system.
  • Drives central sensitisation.
    • By chemokines and cytokines, which act as receptors on astrocytes.

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  • Describe cortical reorganisation (use example from lecture).
  • How is the example from the lecture treated?

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  • Severe neuropathic pain → not using arm -→ cortical representation shrinks down to nearly nothing.
    • Patient says arm feels like foreign body.
  • Treat with rehabilitation program.


  • What are the 3 L's of diagnosing neuropathic pain?
    • What sort of questions/inquiries are made?
  • What are common characteristics described by the patient?
    • +/- signs and symptoms?
  • What is the most common presentation?
  • What are two validated tests for neuropathic pain?

  • Listen to patient history.
    • Described as like '24/7 hitting the funny bone' pain.
  • Look for sensory deficit.
  • Locate what could be a lesion.


  • Burning, shock-like, pins and needles.
  • NOTE: Lancinating (piercing or stabbing) pain most common in patients with neuropathic pain.

Most common presentation: Co-existence of positive and negative neurological signs.


  • DN4 diagnostic questionnaire.
    • Distinguishes nociceptive and neuropathic pain.
    • Completed by physician.
  • painDETECT.
    • Completed by patient.




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What are the three most common comorbidities of neuropathic pain?

  • Difficulty sleeping.
  • Lack of energy.
  • Drowsiness.

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  • What is the most common pharmacological intervention prescribed for neuropathic pain.
    • Why does this present a problem?
  • What four drugs SHOULD be being prescribed? (i.e. have establised efficacy).


    • Have no effect on neuropathic pain.

SHOULD BE USED (top 2 = strong recommendation, second 2 = weak recommendation)

  • Antidepressants and mood stabilisers.

  • Anticonvulsants.

  • Local anaesthetics.

  • Opioids.

    • Rare to use.

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What are the three concepts for treatment of neuropathic pain?

  • “Dampen down” peripheral sensitization in the damaged axon.
    • Sodium channel blockade.
  • “Dampen down” central sensitization.
    • NMDA antagonists.
      • Less glutamate action.
      • Example = ketamine.
    • Calcium channel blockade.
  • Enhancing descending inhibitory pathways.
    • Tricyclics.
    • SNRIs.
    • Tramadol.


  • Best documented analgesic for neuropathic pain?
    • Which one to use?
      • How is it given to patients?

  • TCAs (tricyclic antidepressants).
    • Amitriptyline.
      • Start on low dose so there's a higher chance of compliance.
      • Effects can be slow (4-6 weeks), needs to be given time.


  • What SNRIs are effective in the treatment of neuropathic pain?
  • What SSRIs are effective in the treatment of neuropathic pain?

  • Venlafaxine or duloxetine.
    • More data for duloxetine.
  • None.
    • Noradrenergic effect necessary, hence use of SNRIs and TCAs.


  • What are two anticonvulsants that have therapeutic effect against neuropathic pain?
    • Are they good as anticonvulsants?
  • Not all anticonvulsants work. Give counterxamples.

  • Pregabalin + gabapentin has strong evidence.
    • Not very good as anticonvulsants, but good for NP pain.
  • Valproate - no evidence from RCTs.
  • Carbamazepine - trigeminal neuralgia and facial neuropathic pain only.


  • What is the common mechanism of action of the two anticonvulsant drugs, pregabalin and gabapentin?


  • Binds to the α-2-δ subunit of the voltage-gated calcium channels.
  • Normalises influx of Ca into pre-synaptic cell.
  • Less excitatory neurotransmitter (glutamate) from pre-synaptic cell.
    • Reduction of central sensitisation.


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  • Are opioids effective in treatment of neuropathic pain?
    • If effective, what line of therapy are they?
    • If effective, give examples of what could be used.

  • Opioids are effective in neuropathic pain; however, not always necessary. Strong opioids have a risk of abuse, and there’s few long-term safety trials that have been conducted.
    • Second/third line therapy.
    • Tramadol = #1 (noradrenergic and serotoninergic effect).
    • Tapentadol (noradrenergic effect).
    • Buprenorphine.
    • Methadone.


  • Give an example of a pharmacological intervention for localised neuropathic pain.
    • How does it work?

  • Lidocaine.
    • Blocks the voltage-gated Na+ channels in the neuronal cell membrane responsible for signal propagation.
    • Actional potential not transmitted.


What class of drug has NO evidence of efficacy in cases of neuropathic pain? Explain.

  • There is zero evidence for cannabinoids in NP pain.

  • At high enough doses, it alters the mind of patient experiencing pain, so false evidence of pain reduction.


Treatment guidlines.

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