Benzodiazepines analgesia and cognition

Question 1

Action of intrathecal diazepam

Answer 1

suppresses sensitised response to heat and mechanical stimulation

Question 2

Measuring heat hyperalgesia

Answer 2

paw withdrawal latency upon exposure to defined radiant heat

Question 3

Measuring mechanical sensitisation

Answer 3

paw withdrawal from Von-Frey filaments (varying size of filament)

Question 4

Measuring cold allodynia

Answer 4

time spent lifting, shaking or licking paw after drop of acetone on injured paw

Question 5

What receptors mediate analgesic effects of intrathecal diazepam

Answer 5

alpha2/3-GABA(A)Rs

Question 6

a2-GABA(A)Rs

Answer 6

• analgesic target for subtype of selective benzodiazepines
• densely expressed in mouse lamina II/III dorsal horn neurons and in primary afferent dorsal root ganglion neurons
• intrathecal diazepam suppresses response to heat and mechanical stimulation in a1H101R but not a2H101R

Question 7

a5-NAMs

Answer 7

exhibit pro-cognitive properties

Question 8

a5-GABA(A)Rs and cognition

Answer 8

• expressed extrasynaptically in hippocampal CA1 neurons
• mediate tonic current
• a5 knock out mouse exhibits improved performance in water maze
• cognitive impairing effects absent in a5 knock out mouse
• NAMs of a5-GABAAR improve cognitive performance and enhance LTP
• NAMs act on benzodiazepine binding site and are being assessed in clinical trials for cognitive disorders, depression and stroke

Question 9

Action of benzodiazepines in a1

Answer 9

sedative

Question 10

Action of benzodiazepines in a2

Answer 10

anxiolytic and analgesic

Question 11

Action of benzodiazepines in a5

Answer 11

impaired cognition