230 - Pain

Question 1

What is congenital insensitivity to pain (CIP)?

Answer 1

condition with absent or reduced pain sensation caused by Na channel mutations

Question 2

what is nociception?

Answer 2

sensory process that provides signal triggering pain. Pain may occur without nociception and nociception may not always lead to pain

Question 3

what is classified as chronic pain?

Answer 3

pain persisting beyond normal healing (>3-6months)

Question 4

what is dysasthesia?

Answer 4

abnormal unpleasant sensation

Question 5

what is an increased pain response to noxious stimuli called?

Answer 5

hyperalgesia

Question 6

what is a pain response to non noxious stimuli called?

Answer 6

allodynia

Question 7

what is paraesthesia?

Answer 7

pain response in the absence of stimulus

Question 8

what is hyperpathia?

Answer 8

pain threshold increased but increased pain response when threshold passed

Question 9

describe the reflex arc

Answer 9

afferent nociceptive fibre (free nerve endings) carries signal from stimulus and synapses with interneuron in dorsal horn (substantia gelatinosa). Signal sent to brain via ascending pathways but interneuron also synapses with an efferent motor neuron in ventral horn and impulse travels to effector muscle bypassing brain

Question 10

what do meissners and pacinian corpuscles sense?

Answer 10

pressure and vibration in skin

Question 11

what are the 3 types of nociceptors?

Answer 11

• TRPV1 (capsaicin) incr temp receptor - depolarises >43C causing burning sensation (also depolarised with chili)
• chemical receptors - depolarise on binding to inflammatory cytokines (histamine, bradykinin, prostaglandins)
• mechanical receptors - depolarise on excessive stretch

Question 12

what are the types of nociceptive fibres (1st order)?

Answer 12

• Adelta (III) - fast myelinated pain fibres sensing first pain. Also unimodal - only sense 1 type of pain to give sharp localised pain
• C (IV) - slow unmyelinated pain fibres but polymodal and transmit distinguishable types of pain. Produce dull ache of distinguishable type
• Abeta (II) - inhibit pain signals at dorsal horn - rubbing sore area provides pain relief

Question 13

what are 2nd order nociceptive fibres?

Answer 13

The ascending pathways

• cross spinal cord at entry level
• ascend in spinothalamic tract synapsing in the ventral postero-lateral nucleus (VPL) of thalamus

Question 14

what happens at the ventral postero-lateral nucleus of the thalamus?

Answer 14

receives signal from ascending pathways and other regions, carries out filtering/processing then sends projections to the cerebral cortex via the thalamocortical pathways (3rd order neuron). Here insula and cingulate cortices create unpleasant sensation and 1ry somatosensory cortex (sensory homunculus) locates painful stimuli

Question 15

what do the descending pathways do?

Answer 15

Modulation of ascending pathways

• descending opioid/serotingergic pathway - peri acqueductal grey matter of midbrain sends opioidergic projections to the Nucleus Raphe Magnus of the medulla which sends serotinergic projections to dorsal horns via reticulospinal tracts which synapse with interneurons
• Descending Noradrenergic Pathway - Locus Coeruleus of the Pons sends adrenergic projections to dorsal horns and synapse with interneurons

Question 16

how does down regulation work?

Answer 16

Pathways synapse with and stimulate interneurons which have an inhibitory action on 1st and 2nd order nociceptive fibre synapses by releasing enkephalins. These inhibit pre-synaptic neurotransmitter release and hyperpolarise the post-synaptic membrane

Question 17

what is stressed induce analgesia?

Answer 17

in stress the amygdala stimulates peri-aqueductal grey matter to release opioid onto nucleus Raphe Magnus (descending opioid/serotingergic pathway) causing inhibition

Question 18

How does inflammation cause pain?

Answer 18

nociceptors sensitised by inflammatory mediators - Prostaglandin (synthesised by COX which is inhibited by aspirin), substance P, bradykinin and histamine (all peptides). This contributes to more inflammation (vaso dilatation) and mast cell degranulation

Question 19

what is referred pain?

Answer 19

Internal organs have 1st order nociceptive fibres but no 2nd order. Instead the 1st order synapse with 2nd order of fibres from skin at entry level so the brain interprets this as signals coming from the skin

Question 20

how do different analgesics work?

Answer 20

• Local anaesthetics - block transmission of noxious stimulants to spinal cord at site
• NSAIDs - reduce inflammation thereby reducing impulses from certain nociceptors
• Opioids - act on desc pathways, directly inhibit nociceptive signals at 1st order nociceptor/dorsal horn synapse and blunt emotional aspects of pain
• General anaesthetics - unknown mechanism

Question 21

what are the types of opioid receptors?

Answer 21

All metabotropic (G-protein coupled) so modulate neurotransmission rather than ion channels (slow acting)
*MU
*delta
*kappa
Mu and delta most potent analgesic effects and Mu are the most addictive

Question 22

what type of endogenous opioids are there?

Answer 22

• endorphins - all 3 receptors but highest affinity for mu
• enkephalins - primarily delta agonists
• Dynorphins - primarily kappa agonists

Question 23

what effect do opioids have?

Answer 23

analgesia, euphoria, sedation, cough suppression, constipation, resp depression NandV, miosis

people become tolerant (reduced effect), dependent (withdrawal leads to symptoms) but only those pre-disposed to addiction become addicted

Question 24

what is neuropathic pain?

Answer 24

neuronal damage caused by neuropathies, nerve avulsions, cancers, infections, amputations, MS, spinal cord damage, stroke.
Effects: inflammation (Na channel abnormalities), incr sympathetic activity, sensitisation of dorsal horn and central sensitisation and reorganisation.

Question 25

what is phantom limb pain?

Answer 25

perception of pain in a limb that is no longer there (80% of amputees) due to:

• prolonged nociceptor sensitisation
• dorsal horn reorganisation(alphaB fibres sprout and synapse on 2nd order neurotransmitters
• somatosensory cortex reorganisation (adjacent limbs invade redundant cortex)
• mismatch between sensory, visual and motor activities (Rx mirror visual feedback)

Question 26

how does paracetamol work as an analgesic?

Answer 26

• inhibits Cyclo-Oxygenase and therefore prostaglandin production. Also anti pyrexial.
• Inhibits anandamine (endocannabinoid) take up by neurons
• inhibits CNS NA channels > analgesic

Question 27

what are the effects of paracetamol OD?

Answer 27

*Toxic phase I byproduct (N-acetyl-P-BenzoQuinoneimine) conjugates glutathione > liver damage
*causes NandV and anorexia after 24hrs
*causes abdo pain, hyper/hypoglycaemia, metabolic problems after 3-5 days
Treat with N-acetylcysteine or methionine

Question 28

how do NSAIDs work as an analgesic?

Answer 28

*competitively inhibit COX 1 and 2 enzymes. COX2 responsible for converting arachidonic acid to prostaglandins (inflammation)

Question 29

what are non selective COX inhibitors and selective COX2 inhibitors?

Answer 29

• non selective COX inhibitors - ibuprofen, naproxen, diclofenac - s/e GI irritation and ulceration
• selective COX2 inhibitors - celecoxib and etoricoxib - s/e MI and stoke risk

Question 30

how do opiates act as an analgesic?

Answer 30

• inhibit ascending pain pathways - binding to opioid receptors induces K influx into presynaptic membrane between 1st and 2nd nociceptive fibres causing hyperpolarisation
• indirect inhibition via activation of descending pathways

Question 31

what properties does tramadol have?

Answer 31

• opiod properties - mu

* non opioid - acts as a SNRI