Flashcards in Lecture 28 - Neuropathic pain and analgesia 1 Deck (16):
Chronic pain is pain for over ...
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?
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?
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
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
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