Lecture 28 - Neuropathic pain and analgesia 1 Flashcards Preview

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Flashcards in Lecture 28 - Neuropathic pain and analgesia 1 Deck (16):

Chronic pain is pain for over ...

3 months

20% of Australians suffer chronic pain


What are the 3 broad cagetories of chronic pain?

1) defined nociceptive basis (chronic arthritis) -

2) well-defined neuropathological basis - shingles, phantom limb pain, from tumour, SC compression

3) idiopathic - pathogenesis not well accepted


What is neuropathic pain?

Pain generated and perpetuated by the NS

May be iniated by trivial injury to CNS/PNS

Pain becomes independence of initial triggered injury

lasts indefinitely and may escalate over time

response to conventional analgesics is poor

prevalence is increasing


What are the characterists of neuropathic pain?

Spontaneous pain


Allodynia - pain in response to a nromally innocuous stimulus
- light touch
hot or cold


What is the value of animal models in pain research?

standardisation of genetic and enviro. backgrounds

allow controlled investigation of chronic pain conditions


Do animal models predict analgesic efficacy in humans?

all human pain realted moleucles have a rodent counterpart

but has been cases of failed efficacy in man


What is an acute pain test for rodents?

tail flick test - latency in moving tail in response to heat stimulus


What is the von frey test?

assessment of tactile allodynia

measures foot withdrawal threshold to light tough


Describe the voltage gates Ca channel?

4 subunits

a subunit - 4 domains, each with 6 transmembrane segments - forms the pore

b subunit - intracellular

y subunit - 4 transmembrane segments

gamma subunit - 1 transmembrane segment


how many different genes encod the a subunit?


Therapeutically0used modulators differ for some


What is the significance of the a(2)-gamma protein?

accessory subunit of voltage gated Ca2+ channels

modifies channel function properties when present
- increases time to inactivation
- thus increase Ca2+ current

Subunits UP-REGULATED in DRG and central terminals in neuropathic pain


What is gabapentin (Pregabalin)?

antiepilepsy drugs shown in clinical trials to be effective in management of neuropathic pain

deseigned to mimic NT Gaba, but

- do not interact with GABA receptors
- are not metabolised to GABA
- do not block GABA reuptake or metabolism



Where does gabapentin & Pregabalin bind then, and how does it work?

to the a(2)-delta bind site. (Blocks the normal a(2)-gamma protein)

decreases the Ca2+ influx at pre-synaptic terminals in hyperexcited nerons

termed "modulator"

ultimately decrease the release of excitatory NTs as less Ca2+ is entering the nerve terminal


What is the signifance of Pregabalin in neuropathic pain then?

high bioavailability - 90%

fast onset - administered twice daily

improves disturbed sleep/anxiety

well tolerated

1st line therapy (might be good to be used in conjunction with morphine)


Which receptors do conatokins






conatokins - NMDA

w-conatonxins - Ca2+ channels

u-conotoxins - Na+ channels


k-conotoxins - K+ channels


w-conatonxins can been made synthetically in the form of...

Ziconotide - blocks Ca2+ channels - therefore inhibits pain transmission in SC

needs to be administeed via intrathecal catheter straight to SC to avoid side effects with sympathetic nerves when given intravenously

no evidence of tolerance increase