Neuropathic pain

Question 1

What is the difference between nociception and pain perception

Answer 1

Nociception
- detection of noxious stimuli by specialised peripheral receptors

Pain perception
- interpretation of the noxious signals in the brain

Question 2

What are the changes induced by chronic (maladaptative) pain in the nervous system

Answer 2

Chronic pain will result in neuroplastic changes in the nervous system leading to:
- amplified pain signals
- altered pain parception
- changes in emotional processing

Question 3

Give some examples for chronic pain syndromes

Answer 3

Chronic musculoskeletal pain
- osteoarthritis
- DJD

Chronic visceral pain
- cystitis
- IBD
- pancreatitis

Chronic peripheral neuropathic pain
- tail mutilation
- painful radiculopathy
- FOPS

Chronic central neuropathic pain
- spinal cord injury
- brain injury

Chronic cancer-related pain
- bone neoplasia
- tumors causing spinal cord or nerve root compression
- abdominal masses causing visceral pain
- oral squamous cell carcinoma

Chronic postsurgical or post-traumatic pain
- oral pain (e.g., dental disease)
- limb/tail amputation

Question 4

What is neuropathic pain

Answer 4

Neuropathic pain is a subcategory of chronic pain that is a consequence of damage to or dysfunction of the nervous system

It is characterized by:
- spontaneous pain
- heightened sensitivity to touch
- abnormal sensations

Question 5

What is the pathomechanism supporting neuropathic pain

Answer 5

There are three fundamental phenomena intrinsic to the development of neuropathic pain:
- central sensitisation
- central disinhibition
- phenotypic changes

Question 6

What is central sensitisation

Answer 6

Central sensitisation is the amplification of pain signal processing as it travels to the brain, leading to increased pain sensitivity, allodynia and hyperalgesia

The spinal cord and medullary dorsal horn neurons play a crucial role in pain perception through a mechanism known as “wind-up”
- it involves substance P (neurokinin-1 receptors) and glutamate (NMDA receptors)

Question 7

What is central disinhibition

Answer 7

Central dishinbition refers to an imbalance between excitatory and inhibitory side of the nervous system, such that there is reduced inhibition to the spinal cord dorsal horn

Question 8

What is phenotypic change

Answer 8

In response to ongoing pain signals, injury or inflammation, neurons and gial cells may undergo phenotypic changes

These changes can include:
- increased expression of pain-related receptors
- altered neurotransmitter release
- enhanced synaptic plasticity

Question 9

Explain why NSAIDs can be useful in neuropathic pain management

Answer 9

They do not have a sedative adverse effect and/or may allow a reduction in the dose of a drug with sedative effects

Cyclooxygenase 2 mediated prostaglandins, such as prostaglandin E2, contribute to the development of neuropathic pain
- in the CNS, PGE2 modulates pain sensitivity and, in the peripheral nervous system, PGE2 sensitises nociceptive afferent neurons through E-prostanoid receptors

Question 10

What would be your treatment plan for peripheral neuropathic pain

Answer 10

First line therapy (4-week trial)
- anti-NGF monoclonal antibody (chronic painful stimuli increase NGF which in turn leads to central and peripheral sensitisation and neurogenic inflammation)
- glucocorticoids (block transcription of inflammatory gene among other)
- prednisolone 0.5-1 mg/kg, PO, q24h then taper

Second line therapy (4-8-week trial)
- combination of first-line therapy
- combination of first-line therapy and ketamine SC (0.5 mg/kg, SC every 4 weeks)
- ketamine is an NMDA receptoor antagonist

Third-line therapy (8-week trial)
- Oral NMDA receptor antagonist (amantadine 3-5 mg/kg, PO, q12-24h)
- tramadol (1-2 mg/kg, PO, q12-24h)
- amitrytyline (0.5-4 mg/kg, PO, q12-24h)