T.P. - lost in translation

Question 1

What is chronic pain?

Answer 1

IASP: ‘Pain without biological value that has persisted beyond the normal tissue healing time’ (>3 months)

5 million in UK develop CP annually
Only 2/3rds will recover that year (Chief Medical Officer’s report 2009)

• Back pain = £12.3 billion/year (cost of pain from all causes much higher)

Question 2

What is neuropathic pain?

Answer 2

‘Pain resulting from damage to the nervous system’ (sensory pathway)

Characteristically:

• odd symptoms (spontaneous pains without provocation or tissue injury - out of proportion)
• often chronic (i.e. >3months)
• difficult to treat using conventional analgesics e.g. ibuprofen, morphine

Surprisingly common:
- estimated as affecting 1.5% of US population

Examples of neuropathic pains:

• diabetic, trigeminal & post-herpetic neuralgia
• post-stroke, phantom limb, MS pains

Question 3

Current treatment for NP pain (general)

Answer 3

Drugs

• conventional analgesics (opiates, NSAIDs)
• antidepressants, anticonvulsants (most effective we have but still not effective)
• topical lidocaine/capsaicin
• ketamine, cannabinoids

Interventional

• nerve blocks / epidural steroids
• spinal cord stimulators / TENS (transcutaneous electrical nerve stimulation)

Therapy

* psychological - CBT
* physiotherapy
* relaxation

Question 4

Effectiveness of current treatments - as shown by Finnerup et al (2015)

Answer 4

Series of meta-analyses summarising effectiveness of treatments (from RCTs)

At best, TREAT between 2-6 patients for ONE patient to get 50% improvement in pain

Also treat 5-20 patients to HARM one
* not a good risk/benefit balance

Question 5

Describe substance P discovery

Answer 5

First isolated by von Euler & Gaddum (1931) - powdery substance

Caused hypotension & smooth muscle relaxation

• Abundant: especially in dorsal horn of cord
• Amino acid structure: undecapeptide (11 amino acids) - (1970)

*Lembeck (1953) proposed role as pain transmitter

Question 6

Describe substance P discovery

Answer 6

First isolated by von Euler & Gaddum (1931) - powdery substance

Caused hypotension & smooth muscle relaxation. Lembeck (1953) proposed role as pain transmitter.

Abundant: especially in dorsal horn of cord (lamina I-III)

1970: Amino acid structure = undecapeptide (11 amino acids).

Question 7

What did Nilsson (1974) show about SP?

Answer 7

Immunocytochemistry showed high levels of SP in Lamina I-III

Present in small DRG cell bodies

* 6-20% of all DRG cells
* small cells = nociceptors with C afferents

*Estimated to be in 50% of all C-fibre neurones (nociceptors) - (McCarthy & Lawson 1989) - supports involvement in nociceptive transmission

Question 8

What did Takahashi & Otsuka (1975) show about SP?

Answer 8

Spinal SP levels drop when dorsal roots sectioned

*Cut afferents - axons in cord degenerate: Suggests that lots of the SP in the spinal cord was coming from the afferents (suggests it is release from the afferents)