March 20 - Neuropathic Pain

Question 1

What is pain?

Answer 1

It is defined as “an unpleasant sensory and emotional experience associated with actual or potential tissue damage, or described in terms of such damage”. Pain can either be chronic (long term) or acute (short term)

Question 2

What are the two main types of pain?

Answer 2

Nociceptive

Neuropathic

Question 3

What is nociceptive pain?

Answer 3

A nociceptor (pain receptor) is stimulated by a noxious or potentially damaging stimuli through mechanical, thermal or chemical means which is associated with inflammation

Question 4

What is neuropathic pain?

Answer 4

Pain initiated by a lesion or dysfunction of the somatosensory system, resulting in abnormal activity of the nociceptive pathway. Damage can result from drugs, disease or trauma

Question 5

What are triggers of neuropathic pain?

Answer 5

Alcoholism, amputation, diabetes, drugs (ex. chemotherapy), herpes zoster (shingles), HIV infection/AIDS, multiple sclerosis, spinal injury, stroke, tumour

Question 6

What are the nerve fibres involved with neuropathic pain?

Answer 6

Small, myelinated A-delta fibres (pain/temperature)
Small, unmyelinated C fibres (pain/temperature)
Large, myelinated A-beta (touch)

Question 7

What is the importance of A-delta/C fibres in neuropathic pain?

Answer 7

A-delta and C fibres originally start the pain cascade and then can turn off, but in chronic pain these pain fibres don’t turn off.

Question 8

What is the importance of A-beta fibres in neuropathic pain?

Answer 8

In chronic pain syndroms, these fibres are recruited last in the development of chronic pain

Question 9

Describe the pain pathway

Answer 9

Pain impulses travel down primary afferent nerve fibres (A-delta/C fibres) from the stimulus to the dorsal root ganglia (DRG). The DRG sends the signal to the dorsal horn of the spinal cord. The pain impulse travels via ascending pathways and excites a certain area of the brain. The brain sends anti-nociceptive signals to shut off the incoming pain response

Question 10

What are anti-nociceptive signals released by the brain?

Answer 10

The brain releases anti-nociceptive substances such as noradrenaline, adrenaline, GABA, serotonin, endogenous opioids (endorphins, enkephalins), endogenous cannabinoids

Question 11

What are neurotransmitters involved in the pain pathway?

Answer 11

Excitatory neurotransmitters bind to post-synpatic receptors and cause depolarization (e.g., glutatmate binds to A-beta fibres, substance P binds to C fibres)
Inhibitory neurotransmitters bind to post-synaptic receptors and cause hyperpolarization (e.g., GABA, glycine bind to inter-neuronal fibres)

Question 12

Describe the pathophysiology of neuropathic pain

Answer 12

Pain is associated with the hyperexcitability of dorsal horn neurons. Hyperexcitability is due to either enhancement of excitatory mechanisms and/or loss or reduction in inhibition.

Question 13

Describe “windup” pathophysiology

Answer 13

Occurs when adjacent neurons product action potentials in response to ectopic firing thereby increasing the strength of the pain signal. If neuropathic pain isn’t treated, it will get worse

Question 14

Describe the symptoms of neuropathic pain

Answer 14

They are extremely unpredictable (persistent or intermittent)Symptoms vary greatly depending on: severity, intensity, location

Question 15

What are symptoms of neuropathic pain?

Answer 15

Pins and needles, burning, shooting, stabbing, numbness, tingling, jabbing, throbbing, aching

Question 16

What is allodynia?

Answer 16

Pain due to stimulus that doesn’t normally provoke pain. Exaggerated pain symptoms from non-noxious stimuli. It is caused by the recruitment of A-beta fibres

Question 17

What is hyperalgesia?

Answer 17

Pain response greater than usual to a stimulus that is normally painful. Exaggerated pain symptoms from noxious stimuli.

Question 18

What is paraesthesia?

Answer 18

Abnormal numbing or prickling of the skin (pins and needles)

Question 19

What is the pain triad?

Answer 19

Chronic pain sufferers usually develop additional disorders such as: insomnia, fatigue, lack of concentration, stress, depressioin, anxiety

Question 20

How is neuropathic pain diagnosed?

Answer 20

If the patient clinically presents with 3-4 classic symptoms
If the patient scores a four or more on the DN4 questionnaire
If the patient scores over 4 on the visual analogue scale

Question 21

What are the 4 points of focus in the treatment of neuropathic pain?

Answer 21

1) Inhibition of the 1st sensory afferent (maybe something topical to stop the pain at that site and it won’t be transmitted)
2) Synaptic inhibition between 1st order sensory afferent and DRG (the presynaptic delivery of the nociceptive mediators into the spinal cord)
3) Synaptic inhibition between the DRG and dorsal horn interneurons (shut down the the dorsal horn interneuron via Na channel blockers, Ca channel blockers, GABA agonist, etc.)
4) Descending anti-nociceptive pathways - turn them on

Question 22

How is neuropathic pain treated?

Answer 22

Action potentials can be regulated by decreasing excitation or increasing inhibition. Decrease excitation: Na channel blockers, inhibiting calcium channels or blocking excitatory receptors. Increasing inhibition: GABA agonists, inhibition of serotonin and noradrenaline reuptake

Question 23

What are the three main pharmacological agents used to treat neuropathic pain?

Answer 23

Antiepileptics
Anti-depressants
Topical anti-neuralgic agents

Question 24

How do antiepileptics works to treat neuropathic pain?

Answer 24

Reduce influx of Na and Ca
Enhance inhibitory effects like GABA (dorsal horn, interneurons)
Reduces concentration of glutamate and/or blocks NMDA receptors
Example: gabapentin

Question 25

What types of anti-depressants work to treat neuropathic pain?

Answer 25

Tri-cyclic

Selective serotonin reuptake inhibitors

Question 26

How do tri-cyclic anti-depressants work to treat neuropathic pain?

Answer 26

Blocks reuptake of noradrenaline and serotonin
Blocks Na and Ca channels and NMDA receptors
Ex: amitriptyline

Question 27

How do selective serotonin reuptake inhibitors work to treat neuropathic pain?

Answer 27

Inhibits serotonin reuptake without affecting noradrenaline

Ex: sertraline

Question 28

How to topical anti-neuralgic agents work to treat neuropathic pain?

Answer 28

Exact mechanism is unclear however it has been proposed that these products desensitize afferent neurons by depleting the release of substance P
Ex: capsaicin ointment or lidocaine

Question 29

How do narcotics work to treat neuropathic pain?

Answer 29

Opening potassium channels (allows K to leave the environment of the cell -> suppression of the pain response)

Question 30

What is the goal in the treatment of neuropathic pain?

Answer 30

Although it would be ideal to relieve a patient’s pain entirely, this is not usually the case. Only one in five patients are able to achieve total cessation of pain with treatment. Generally these treatment options only assist in reducing the degree of pain experienced to a more tolerable level (to a point where it does not interfere in their normal daily functioning)