Lecture 28 - Neuropathic pain and analgesia 1

Question 1

Chronic pain is pain for over …

Answer 1

3 months

20% of Australians suffer chronic pain

Question 2

What are the 3 broad cagetories of chronic pain?

Answer 2

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

Question 3

What is neuropathic pain?

Answer 3

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

Question 4

What are the characterists of neuropathic pain?

Answer 4

Spontaneous pain

hpersensitivity

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

Question 5

What is the value of animal models in pain research?

Answer 5

standardisation of genetic and enviro. backgrounds

allow controlled investigation of chronic pain conditions

Question 6

Do animal models predict analgesic efficacy in humans?

Answer 6

all human pain realted moleucles have a rodent counterpart

but has been cases of failed efficacy in man

Question 7

What is an acute pain test for rodents?

Answer 7

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

Question 8

What is the von frey test?

Answer 8

assessment of tactile allodynia

measures foot withdrawal threshold to light tough

Question 9

Describe the voltage gates Ca channel?

Answer 9

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

Question 10

how many different genes encod the a subunit?

Answer 10

10

Therapeutically0used modulators differ for some

Question 11

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

Answer 11

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

Question 12

What is gabapentin (Pregabalin)?

Answer 12

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

??

Question 13

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

Answer 13

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

Question 14

What is the signifance of Pregabalin in neuropathic pain then?

Answer 14

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)

Question 15

Which receptors do conatokins

w-conatonxins

u-conotoxins

and

k-conotoxins

target?

Answer 15

conatokins - NMDA

w-conatonxins - Ca2+ channels

u-conotoxins - Na+ channels

and

k-conotoxins - K+ channels

Question 16

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

Answer 16

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