sodium channels and pain 1 Flashcards

1
Q

what is pain defined as?

A
  • pain is an unpleasent sensory or emotional experience associated with actual or potential tissue damage.
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2
Q

give stages of how pain is reached by the brain?

A

-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

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3
Q

what is nociception?

A

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

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4
Q

give steps of a spinal cord reflex?

A
  • sensory receptor
  • afferent pathway
  • integrating centre
  • efferent pathway
  • effector organs
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5
Q

what is a DRG neuron and what do they do?

A
  • DRG is dorsal root ganglion neuron

- relay information from the periphery to the spinal cord

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6
Q

what is noxious stimuli?

A

Stimuli which is an actually or potentially tissue damaging event

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7
Q

what is non-noxious stimuli?

A

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

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8
Q

explain why DRG are part of a heterogenous population

A
  • because DRG come in different sizes

- they can respond to different stimuli

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9
Q

what do different sizes of DRG respond to?

A
  • large - non-noxious stimuli e.g. touch
  • medium - noxious stimuli -pain sensing (nociceptive)
  • small - noxious stimuli - pain sensing (nociceptive)
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10
Q

what are the 3 key components in pain sensing?

A
  • transduction
  • conduction
  • transmission
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11
Q

what are the different myelination of nociceptors?

A

Ab - thick
Adelta - thin myelination
C- no myelination

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12
Q

what is transduction?

A
  • 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?
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13
Q

what is involved in the conudction of pain?

A

-dorsal root ganglion conducts to SC?

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14
Q

what is involved in the transmission of a pain stimulus?

A
  • spinal cord central termini
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15
Q

Define accute pain

A

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

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16
Q

Define chronic pain?

A
  • 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.
17
Q

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

A

19% of europeans suffer moderate to severe chronic pain

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

18
Q

What are NSAID?

A
  • 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.
19
Q

what are opioids?

A

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.
20
Q

why is pain important?

A

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.

21
Q

give conditions in which patients feel extreme pain

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

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

22
Q

give conditions in which patients have the absence of pain

A

CIP - complete insensitivity to pain

recessive

23
Q

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

A
  • 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
24
Q

how many VGSCs are there?

A

9

Nav1.1 to Nav 1.9

25
Q

what differs between different VGSC s/alpha subunits?

A
  • 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
26
Q

Where are Nav1.7-1.9 expressed?

A

exclusively in PNS

good targets for pain therapy

27
Q

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

A

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