Flashcards in 230 - Pain Deck (31):
What is congenital insensitivity to pain (CIP)?
condition with absent or reduced pain sensation caused by Na channel mutations
what is nociception?
sensory process that provides signal triggering pain. Pain may occur without nociception and nociception may not always lead to pain
what is classified as chronic pain?
pain persisting beyond normal healing (>3-6months)
what is dysasthesia?
abnormal unpleasant sensation
what is an increased pain response to noxious stimuli called?
what is a pain response to non noxious stimuli called?
what is paraesthesia?
pain response in the absence of stimulus
what is hyperpathia?
pain threshold increased but increased pain response when threshold passed
describe the reflex arc
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
what do meissners and pacinian corpuscles sense?
pressure and vibration in skin
what are the 3 types of nociceptors?
*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
what are the types of nociceptive fibres (1st order)?
*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
what are 2nd order nociceptive fibres?
The ascending pathways
*cross spinal cord at entry level
*ascend in spinothalamic tract synapsing in the ventral postero-lateral nucleus (VPL) of thalamus
what happens at the ventral postero-lateral nucleus of the thalamus?
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
what do the descending pathways do?
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
how does down regulation work?
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
what is stressed induce analgesia?
in stress the amygdala stimulates peri-aqueductal grey matter to release opioid onto nucleus Raphe Magnus (descending opioid/serotingergic pathway) causing inhibition
How does inflammation cause pain?
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
what is referred pain?
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
how do different analgesics work?
*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
what are the types of opioid receptors?
All metabotropic (G-protein coupled) so modulate neurotransmission rather than ion channels (slow acting)
Mu and delta most potent analgesic effects and Mu are the most addictive
what type of endogenous opioids are there?
*endorphins - all 3 receptors but highest affinity for mu
*enkephalins - primarily delta agonists
*Dynorphins - primarily kappa agonists
what effect do opioids have?
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
what is neuropathic pain?
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.
what is phantom limb pain?
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)
how does paracetamol work as an analgesic?
*inhibits Cyclo-Oxygenase and therefore prostaglandin production. Also anti pyrexial.
*Inhibits anandamine (endocannabinoid) take up by neurons
*inhibits CNS NA channels > analgesic
what are the effects of paracetamol OD?
*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
how do NSAIDs work as an analgesic?
*competitively inhibit COX 1 and 2 enzymes. COX2 responsible for converting arachidonic acid to prostaglandins (inflammation)
what are non selective COX inhibitors and selective COX2 inhibitors?
*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
how do opiates act as an analgesic?
*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