Neuropathic Pain

Question 1

What causes neuropathic pain?

Answer 1

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

Question 2

What are the types of neuropathic pain?

Answer 2

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

Question 3

What causes peripheral neuropathies most commonly?

Answer 3

Metabolic conditions such as diabetes Toxic conditions: Alcohol, chemotherapy, etc Postinfectious (PostHepaticNeuralgia, HIV, CMV)

Question 4

What are the 3 most common causes of central neuropathic pain?

Answer 4

Spinal cord injury Post-stroke pain Multiple sclerosis

Question 5

What causes postraumatic neuropathic pain?

Answer 5

Sciatica Postoperative pain Neuroma/nerve entrapment Phantom limb pain Complex Regional Pain Syndrome (CRPS)

Question 6

How common is neuropathic pain?

Answer 6

20 - 24% of diabetics = peripheral neuropathy 25 - 50% of patients >50 with herpes zoster develop PostHepaticNeuralgia Up to 20% develop post mastectomy pain 1/3rd of cancer patients have neuropathic pain >50% of low back pain patients have associated neuropathic pain

Question 7

What are the physiological mechanisms of peripheral neuropathic pain?

Answer 7

Membrane hyperexcitability (ectopic discharges) Peripheral sensitisation

Question 8

What are the physiological mechanisms of central neuropathic pain?

Answer 8

Membrane hyperexcitability Wind up Central sensitisation Denervation supersensitivity Loss of inhibitory controls

Question 9

How do peripheral pain receptors become hyperexcitable?

Answer 9

Damage to nerves results in overexpression of adrenoreceptors and sodium channels resulting in faster and more frequent action potentials

Question 10

How is central neuropathic pain controlled?

Answer 10

Upregulation of calcium channels. Block is possible by opioid receptors and noradrenaline/serotonin receptors

Question 11

What is homosynaptic sensitization What is the result? What is heterosynaptic sensitization what is the result?

Answer 11

Increased feeling of pain from touch due to convergence with a hyperalgesic interneuron that is also connected to a nociceptor. (hyperalgesia is the result) This is as opposed to allodynia seen in heterosynaptic sensitization where normal touch triggers a pain response.

Question 12

What do glia do to create neuropathic pain?

Answer 12

They produce chemokines and cytokines which desensitize C-fibers to pain

Question 13

What are the symptoms of CRPS?

Answer 13

Hyperalgesia and allodynia

Question 14

How is neuropathic pain diagnosed?

Answer 14

LOOK LISTEN LOCATE Listen to patient history Look for sensory discrepancy. Locate (Think about if pain is neuroanatomically plausable.)

Question 15

What kind of pain is neuropathic pain?

Answer 15

Pins and needles, shock - like, and burning

Question 16

What are the positive and negative signs and symptoms of neuropathic pain?

Answer 16

Positive: Dysesthesias Paresthesias Spontaneous pain Stimulus-evoked pain Negative: Loss/impairment of sensory quality Numbness and reduced sensation

Question 17

Conclusions neuropathic pain:

Answer 17

Result of lesion or disease of somatosensory system Very common but underdiagnosed and undertreated Diagnosed by Look Listen Locate Common presentation consists of positive and negative signs Range of validated tools help with diagnosis Neuropathic pain is terrible for quality of life.

Question 18

What approaches are taken to manage neuropathic pain?

Answer 18

Pharmacotherapy Neurostimulatory therapy Interventional regional anaesthesia Lifestyle Psychological Physical rehabilitation

Question 19

What concepts must be understood for treating neuropathic pain?

Answer 19

“dampen down” peripheral sensitization in damaged axon (sodium channel blockade) “dampen down” central sensitization (NMDA agonists and calcium channel blockers) “enhancing” descending inhibitory pathways (tricyclics/SNRIs, tramadol)

Question 20

Read paper in literature called:

Answer 20

Pharmacotherapy for neuropathic pain in adults: a systematic review and meta-analysis Results show tricyclic antidepressants, serotonin-noradrenaline reuptake inhibitors (SNRIs), pregabalin, and gabapentin are great for first-line therapy for neuropathic pain.

Question 21

What are the issues with taking antidepressants as analgesics?

Answer 21

Low doses increase compliance Often lots of adverse effects Effect needs time

Question 22

What SNRIs are used for neuropathic pain?

Answer 22

Venlafaxine or duloxetine (more data on duloxetine)

Question 23

Which drug types are being investigated for neuropathic pain?

Answer 23

Antidepressants (TCAs, SNRIs) Anticonvulsants (particularly the ones bound to α2-δ subunit of voltage gated calcium channels eg pregabalin) Opioids such as tramadol and tapentadol Lidocaine plaster

Question 24

Which antidepressants have been shown to help with neuropathic pain?

Answer 24

TCAs and SNRIs

Question 25

What does pregablin do to hyperexcited neuron?

Answer 25

It inhibits the calcium channel’s hyperexcitability

Question 26

What is the NNT for pregabalin?

Answer 26

7.7

Question 27

What does NNT mean?

Answer 27

Number needed to treat before 1 person experiences more than 50% pain relief. Low number is a good drug and high number is bad. This is compared to placebo. and does not mean only every 7th patient.

Question 28

Does pregabalin help neuropathic pain patients sleep?

Answer 28

Yes, in fact it does not suppress REM sleep like many other drugs.

Question 29

Do other anticonvulsants besides pregabalin work for neuropathic pain?

Answer 29

No evidence that they do and they are very dangerous. Carbamazepine is only proven to be effective in trigeminal neuralgia and facial pain.

Question 30

Is carbamazepine effective in treating neuropathic pain?

Answer 30

Only in the case of trigeminal neuralgia and facial pain. Carbamazepine has lots of side effects though so it is better to use pregabalin.

Question 31

Are opioids effective in treating neuropathic pain?

Answer 31

Yes, however not always and no necessarily completely.

Question 32

What is the NNT50 of opioids?

Answer 32

4.3

Question 33

What are the most effective opioids for neuropathic pain?

Answer 33

tramadol (noradrenergic and serotoninergic effect) tapentadol (noradrenergic effect) These drugs are weak opioids

Question 34

Why are strong opioids recommended only as second/third line despite established efficacy?

Answer 34

Potential risk for long-term abuse

Question 35

What is the efficacy of lidocaine plaster like?

Answer 35

Regional suppression of ectopic activity and antiallodynic device effect.

Question 36

When is lidocaine commonly used?

Answer 36

First-line treatment for PHN in elderly patients and second line in other localized neuropathic pain (diabetic polyneuropathy and neuroma).

Question 37

How effective are cannabinoids on neuropathic pain?

Answer 37

0 evidence for effectiveness of cannabinoids on neuropathic pain

Question 38

Conclusions regarding neuropathic pain treatment:

Answer 38

Neuropathic pain is unresponsive to analgesics effective in nociceptive pain In neuropathic pain TCAs, SNRIs, and alpha-2-delta modulators are first-line treatments. Topical treatments offer new options with limited systemic effects Opioids are effective but risk profile limits use Combination therapy is promising but not always the best option.

Question 39

Treatments of neuropathic pain:

Answer 39