Pain

Question 1

how does acute pain occur?

Answer 1

activity of nociceptor in response to potentially harmful stimuli

Question 2

what informations do A-delta and C fibres respectively carry?

Answer 2

A-delta fibres: myelinated; first pain, fast, sharp, prickling and well-localised pain
C-fibres: unmyelinated; slow,, dull and diffuse pain

Question 3

what does mutation in Nav1.7 or TrkA cause?

Answer 3

congenital indifference to pain

Question 4

what information does the anterior spinothalamic tract carry?

Answer 4

2nd order neurons carrying input from A-delta fibres (lamina V)

Question 5

which thalamic nuclei does the anterior spinothalamic tract innervate?

Answer 5

VPL and VPM –> somatosensory localisation and intensity of pain
VPI–> secondary somatosensory cortex - cognition and planning

Question 6

what information does the paleospinothalamic tract carry?

Answer 6

2nd order neurons from lamina I with input from C fibres mostly

Question 7

which thalamic nuclei does the paleospinothalamic tract innervate?

Answer 7

mediodorsal nucleus (ventral caudal part) –> anterior cingulate cortex - affective and motivational aspects
medial subnucleus of the posterior group (POm) –> anterior/rostral insular – quality/emotion
these projection bring about the punishing aspects of pain

Question 8

what is peripheral sensitisation?

Answer 8

inflammatory mediators released by damaged tissue make the nociceptors more sensitive to pain and decrease threshold depolarisation - primary hyperalgesia - pain is felt more intensely

Question 9

what is central sensitisation?

Answer 9

prolonged activity of nociceptive afferents increase the excitability of dorsal horn neurons - hyperalgesia
low threshold mechanoreceptors input to second order neurons lead to pain in response to innocuous stimuli - allodynia

Question 10

what neurotransmitters and receptors are involved in central sensitisation

Answer 10

• activation of Ca2+ channels
• removal of Mg2+ from NMDA receptor increases its sensitivity to glutamate
• nociceptors release glutamate substance P, CGRP and BDNF to dorsal form neurons

Question 11

wha tis chronic pain?

Answer 11

pain lasts for more than 12 weeks

Question 12

how does TENS work?

Answer 12

stimulation of non-noxious large afferents (A-beta fibres) activate lamina II inhibitory interneurons which suppresses transmission of neurotransmitters from C fibres to 2nd order neurons and blocks the pain (that’s why rubbing area of injury provides relief)

Question 13

describe the descending inhibitory control of pain.

Answer 13

PAG receive input from nociceptor afferents and act on raphe nuclei and locus coruleus which release 5-HT and noradrenaline. these act on lamina II interneuron which releases enkephalins and GABA to inhibit A-delta and C fibres and dorsal horn neurons.

Question 14

why does acupuncture work?

Answer 14

pain in one area inhibits pain in other areas. painful stimulus activates descending inhibtiory control pathways

Question 15

which brain structures are involved in the perception of intensity of pain?

Answer 15

superior parietal lobe –> insula–> amygdala

• control cognition and attention
• amygdala is involved in the labelling of pain as aversive*

Question 16

which brain structures are involved in the perception of unpleasantness of pain?

Answer 16

ACC–> PFC–> PAG

control of emotion

Question 17

what are the three types of pain?

Answer 17

nociceptive
inflammatory
neuropathic

Question 18

what is the mechanism of action of morphine (opioids)?

Answer 18

acts on mu-opioid receptors to produce analgesia
increase K+ conductance - decreased excitability and decreases Ca2+ influx - decreased neurotransmitter release
-activates descending inhibitory pathways

Question 19

what are the side effects of opioids?

Answer 19

respiratory depression, nausea and vomiting, mitosis, euphoria/dysphoria, drowsiness/lethargy
reduced GI motility, constipation, reduced biliary/pancreatic excretions
urinary urgency, itching

Question 20

name other opioids besides morphine.

Answer 20

fentanyl sufentanil, methadone, heroin, pentazocine, pethidine, dextromoramide, meptazinol

Question 21

what is the mechanism of action of paracetamol?

Answer 21

reduces active oxidised form of COX-2

• decreases PGE2 induced reduction of glycine inhibition of spinal cord cells
• may also inhibit endocannabinoids reuptake

Question 22

why is diclofenac contraindicated in individuals in cardiovascular complication?

Answer 22

significant COX-2 selectivity - inhibits Prostacyclin formation without inhibiting TXA2 production, risk of clotting (stroke MI)

Question 23

what is the mechanism of action of tramadol?

Answer 23

mu-opioid receptor agonist

serotonin and noradrenaline reuptake inhibition

Question 24

what are the side effects of tramadol?

Answer 24

itching, nausea and vomiting, sweating, constipation

Question 25

what drugs are used to treat neuropathic pain?

Answer 25

anticonvulsants and antidepressants

Question 26

what is the mechanism of action of pregabalin?

Answer 26

binds to alpha-2-delta subunit of n-type ca2+ channels and inhibits calcium influx and therefore reduces neurotransmitter (glutamate, substance P, noradrenaline) release

Question 27

what the side effects of pregabalin?

Answer 27

drowsiness, headache, dizziness, | confusion, dry mouth, constipation, tremor, peripheral oedema ,

Question 28

how do carbamazepine and phenytoin reduced neuropathic pain?

Answer 28

decrease activity of sodium channels - less neuronal excitation

Question 29

what is the mechanism of action of amitriptyline (TCA) in treating pain?

Answer 29

- SNRI --> serotonin and noradrenaline involved in descending inhibitory control - acts on NMDA receptor and blocks Na+ and Ca2+ channels - also acts against depression and insomnia associated with chronic pain

Question 30

name some local anaesthetics? | how do they work?

Answer 30

prilocain, bupivacaine, lignocaine | - block Na+ channels

Question 31

what are the side effects of local anaesthetics?

Answer 31

hypotension, respiratory depression, bradycardia

Question 32

name some inhaled and IV general anaesthetics. | how do they act?

Answer 32

inhaled: enflurane, isoflurane, sevoflurane, desflurane, halothane, NO and xenon IV: propofol, etomidate, ketamine

Question 33

what is a side effect of general anaethetics?

Answer 33

CV depression

Question 34

what is trigeminal neuralgia? | how does it occur?

Answer 34

sudden, paroxysmal attacks pop pain, electric shock like, sharp, stabbing pain in the face compression, distortion or stretching of Trigeminal nerve fibres by PICA or AICA

Question 35

how is trigeminal neuralgia treated?

Answer 35

carbamazepine, phenytoin, sodium valproate --> decrease sodium conductance baclofen, clonazepam --> positive allosteric modulator of GABAa receptor

Question 36

which opioid drug is active sublingually?

Answer 36

dextromoramide

Question 37

which opioid has less risk of respiratory depression?

Answer 37

meptazinol

Question 38

which opioid has increasing half life after every administration?

Answer 38

methadone