sodium channels and pain 1

Question 1

what is pain defined as?

Answer 1

• pain is an unpleasent sensory or emotional experience associated with actual or potential tissue damage.

Question 2

give stages of how pain is reached by the brain?

Answer 2

-injury/stimulus
-peripheral nerve
TRANSDUCTION
- dorsal root ganglion
CONDUCTION
- dorsal horn of spinal cord
- ascending pathway
TRANSMISSION
-brain
-descending pathway from brain to spinal cord - coordinates response

Question 3

what is nociception?

Answer 3

PArt of pain pathway but the stage before the brain becomes involved?

Question 4

give steps of a spinal cord reflex?

Answer 4

• sensory receptor
• afferent pathway
• integrating centre
• efferent pathway
• effector organs

Question 5

what is a DRG neuron and what do they do?

Answer 5

• DRG is dorsal root ganglion neuron

- relay information from the periphery to the spinal cord

Question 6

what is noxious stimuli?

Answer 6

Stimuli which is an actually or potentially tissue damaging event

Question 7

what is non-noxious stimuli?

Answer 7

stimuli which has no potential tissue damage - e.g. touch

Question 8

explain why DRG are part of a heterogenous population

Answer 8

• because DRG come in different sizes

- they can respond to different stimuli

Question 9

what do different sizes of DRG respond to?

Answer 9

• large - non-noxious stimuli e.g. touch
• medium - noxious stimuli -pain sensing (nociceptive)
• small - noxious stimuli - pain sensing (nociceptive)

Question 10

what are the 3 key components in pain sensing?

Answer 10

• transduction
• conduction
• transmission

Question 11

what are the different myelination of nociceptors?

Answer 11

Ab - thick
Adelta - thin myelination
C- no myelination

Question 12

what is transduction?

Answer 12

• exchange of one physical stimulus to another - sodium in neuron reach a threshold for Nav to get involved and to reach an AP
• from skin to nerve?

Question 13

what is involved in the conudction of pain?

Answer 13

-dorsal root ganglion conducts to SC?

Question 14

what is involved in the transmission of a pain stimulus?

Answer 14

• spinal cord central termini

Question 15

Define accute pain

Answer 15

acute pain alerts the body of chemical,thermal or mechanical stimuli which has the potential to damage the body
- has a protective role

Question 16

Define chronic pain?

Answer 16

• pain which persists - usually accompanies chronic inflammatory conditions
• neuropathic pain results from damage to the nerve, which can be caused by trauma , diabetes, cancer treatment and herpetic infection.

Question 17

how many people are said to be suffering from chronic pain?

Answer 17

19% of europeans suffer moderate to severe chronic pain

-50% of those feel there is an unmet therapeutic solution to chronic pain

Question 18

What are NSAID?

Answer 18

• non-steroidal anti-inflammatory drugs
• inhibit COX enxymes (which produce prostaglandins)
• side effect - GI tract irritation
• limited use on peple with heart, renal conditions and diabetes.

Question 19

what are opioids?

Answer 19

Class of drugs which bind to opioid receptors in the CNS, PNS and GI tract.

• have short term side effects
• build up tolerance and develop a dependence on them.

Question 20

why is pain important?

Answer 20

pain is important as it has a protective role - if cannot sense pain you cannot sense tissue damage - this means people are unaware that they are harming there body
- results in infection or loss of limbs/finger and deformities etc

GOAL IS TO RELIEVE PAIN BUT NOT TO ABOLISH IT COMPLETELY.

Question 21

give conditions in which patients feel extreme pain

Answer 21

• PE (primary ethermalgia)
• PEPD (paroxysmal extreme pain disorder)

-feel pain when chewing + defecating
(dominant??)

Question 22

give conditions in which patients have the absence of pain

Answer 22

CIP - complete insensitivity to pain

recessive

Question 23

Why are Voltage gated sodium channels (VGSCs) concerned with pain?

Answer 23

• VGSCs are essential for the excitability of mucles and nerves
• concerned with the conduction of pain
• VGSC’s are major targets for local aneasthesia and epilepsy
• with absence of VGSC’s = hypoexcitability/silence
• inherited pain disorders linked to mutations in VGSCs

Question 24

how many VGSCs are there?

Answer 24

9

Nav1.1 to Nav 1.9

Question 25

what differs between different VGSC s/alpha subunits?

Answer 25

• activation and inactivation properties vary
• different neurons can fine tune excitibility
• expression patterns and levels differ
• are specialisations to where different alpha subunits are expressed

Question 26

Where are Nav1.7-1.9 expressed?

Answer 26

exclusively in PNS

good targets for pain therapy

Question 27

Where are Nav 1.1, 1.2, 1.3 and 1.6 expressed?

Answer 27

in both the PNS and CNS - but dont want to target these for pain therapy as are not PNS specific - don’t want to disrupt CNS