Mechanisms of Pain and Analgesia 2 (DONE)

Question 1

Chronic pain resistant to traditional analgesics

Answer 1

Nerve entrapment
Post traumatic pain
Neuralgia
Chronic low back/neck pain
Cancer 
Spasticity
Causalgias
Vascular insufficiencies
Perineal pain

Question 2

Neurogenic inflammation

Answer 2

SP and CGRP released from primary nociceptive afferents- c fibres
Act in the periphery to promote inflammation via their effects on blood vessels and cells of the immune system
This amplifies and sustains the inflammatory response
it may also involve central facilitation leading to pathological hyperalgesia

Question 3

Central facilitation/wind up

Answer 3

Repeated stimulation increases the amplitude of the action potential
This is caused by NMDA glutamate receptors
Can be prevented by:
NSAIDs to reduce peripheral stimulation
At the spinal cord with opioid antagonists
Or reversed with NMDA antagonists in the spinal cord

Question 4

Nefopam

Answer 4

A benzoxazocine related to orphenadrine and diphenhydramine
Gives low level analgesia- centrally acting
No dependence/tolerance
Not a substitute for morphine
0.2-0.6 x potency of morphine
Has a definite ceiling effect
May act by 5HT/NA/DA re-uptake blockade

Question 5

5-HT and pain

Answer 5

Complex bi-directional role of 5-HT transmission at spinal level
5HT3 receptors implicated in nefopam and acetaminophen action- blockade activates descending inhibitory pathways, may be key in allodynia and hyperalgesia
5HT7 may mediate opiate analgesia

Question 6

Noradrenaline

Answer 6

Transmitter of the inhibitory pathway linking the locus coeruleus to the dorsal horn
Tramadol- mild opioid plus increased NA and 5HT transmission- every 4h
Tramacet- tramadol with paracetamol- every 6h

Question 7

Tramadol

Answer 7

2 isomers compliments activity- racemic mix
Often administered in combination with paracetamol
Metabolised by CYP 2D6 (poor metaboliser will egt limited effect)
Interesting pharmacological profile- activity of tramadol or metabolite at mu, kappa and delta receptors, SERT and NET

Question 8

Neuropathic pain

Answer 8

Central neuropathic pain = pain caused by a lesion or disease of the central somatosensory nervous system
Peripheral neuropathic pain = pain caused by a lesion or disease of the peripheral somatosensory nervous system
Amitryptyline, duloxetine, pregabalin and gabapentin are first line treatments for neuropathic pain
Lower doses are often better tolerated so combination therapy often successful
Tramadol can be given as an acute rescue therapy
Carbamazepine for trigeminal neuralgia

Question 9

Anticonvulsants in neuropathic pain

Answer 9

Gabapentin for post herpetic neuralgia
Pregabalin for post herpetic neuralgia, fibromyalgia and neuropathic pain associated with diabetes
Carbamazepine- trigeminal neuralgia
Antidepressants also used in treatment of neuropathic pain (amitriptyline and duloxetine)

Question 10

Management of neuropathic pain

Answer 10

NICE guidance
Carry out regular clinical reviews to assess and monitor the effectiveness of the treatment, assess pain control, impact on lifestyle, physical and psychological wellbeing, adverse effects

Question 11

Cannabinoids

Answer 11

Earliest use of cannabis for pain
Receptors at all levels
THC, anandamide and synthetic cannabinoids effective against thermal, mechano and chemical pain
CB1 agonists effective against hyperalgesia and allodynia
CB2 may be useful in inflammation
Side effects include sedation, nausea and dizziness
Clinical use in MS only