Neurology of Pain Flashcards
Define pain
An unpleasant sensory and emotional experience associated with actual or potential tissue damage
What is Congenital insensitivity to pain?
Condition with decreased or absent pain sensation caused by:
Na+ channel mutations, other conditions (Genetic usually)
What is nociception?
The sensory process that provides the signals triggering pain
What is chronic pain?
Pain that persists beyond normal healing time (> 3-6 months)
- pathological process (involving nervous system)
- may include biopsychosocial element
Define dysaesthesia
Abnormal, unpleasant sensation (not pain itself)
Define hyperalgesia
Increased pain response to noxious stimuli
Define allodynia
pain response to non-noxious stimuli
Define paraesthesia
Pain response in absence of any stumulus
- i.e. paroxysms = spontaneous shooting pains
Define hyperathia
Pain threshold actually increased but increased pain response when threshold is passed
Describe the reflex arc
Nociceptive fibre (afferent)
- > interneuron in substantia gelantinosa (dorsal horn)
- > motor neurone (ventral horn of spinal cord)
- > impulse travels to effector muscles
Describe the substantia gelatinosa
Located in dorsal horn of spinal cord
Sends fibres up to brain via ascending pathways after receiving signal from nociceptive fibres
Send projections to anterior horn (reflex arc)
Synapse with descending pathways which modulate impulse transmission
What are nociceptors?
Free nerve endings, i.e. not specialised structures
Give examples of nociceptors
TRPV1 (Capsaicin receptor) = temperature receptor
Chemical receptors - inflammation receptors
Mechanical receptors - stretch receptors
What are the main types of 1st-order nociceptive fibres?
A-delta fibres (type III fibres)
C fibres (type IV fibres)
Describe A-delta fibres
Fast pain fibres (myelinated)
Unimodal (one type of pain = sharp,local)
e.g. muscle spindle, golgi tendon organ pain
Describe C fibres (type IV fibres)
Slow pain fibres (unmyelinated)
Polymodal (distinguishable types of pain)
e.g. temp, stretch, inflammation
What are A-beta fibres (Type II)?
Transmit crude touch (i.e. non-pain fibres)
- inhibit pain signals at dorsal horn
e. g. rubbing sore area relieves pain
Describe 2nd order nociceptive fibres?
- where they deccusate in ascending pathway
- which tract they ascend in
- where they synapse in the brain
Decussate at level of entry in spinal cord
Ascend in spinothalamic tract
Synapse in ventro postero-lateral nucleus of thalamus
Send projections to cerebral cortex
- insula and cingulate
- primary somatosensory cortex
What are the insula and cingulate cortices resposnible for in the cerebrum?
Creating unpleasant sensation assoc. with pain
What is the role of primary somatosensory cortex?
Locate painful stimuli
What are the two descending pathways associated with pain?
Descending opioid/Serotinergic pathway
- nucleus raphe magnus (medulla)
Descending noradrenergic pathway
- Locus coeruleus (Pons)
Describe the nucleus raphe magnus
Stimulated by opioidergic projections
Sends serotinergic projections to dorsal horns
Describe the Locus Coerulerus
Sends noradrenergic projections to dorsal horns of spinal cord
Stress induced analgesia occurs how?
Stress induces Amygdala to stimulate per-aqueductal grey matter which stimulates opioid release onto Nucleus Raphe Magnus => descending pathway inhibition results
How do nociceptors become sensitised to inflammation?
Inflammatory mediators act on nociceptors
e.g. prostaglandins, substance P, bradykinin, histamine
Nociceptors also contribute to futher inflammation by release of substance P
What are the effects of substance P?
Mast cell degranulation
Blood vessel vasodilatation
Increased Na+ channel expression in periphery
Increased interneural connectivity
Causes hypersensitisation
Describe how the dorsal horn becomes hypersensitised?
By repeated stimulation of C-fibres => increased glutamate release by 1st order nociceptive fibres
=> opening of NMDA receptors => Ca2+ influx through these NMDA gates causes depolarisation of dorsal horn
=? 2nd order fibres more likely to depolarise and cause hyperalgesia
How does NO induce opioid resistance?
released after Ca2+ influx into post-synaptic fibres
=> stimulates closure of K+ channels o pre-syanptic membrane
- i.e. the opposite to what opioids do (inhibit depolarisation)
Why do we get referred pain from internal organs?
Since organs have 1st order nociceptive fibres only (no devoted 2nd order fibres) which means brain interprets signals as coming from skin
How do NSAIDs work as analgesia?
Reduce inflammation and therfore reduce impulses from certain nociceptors
How do local anaesthetics work as analgesia?
Block transmission of noxious stimulants to spinal cord
How do opioids work as analgesia?
Act on descending pain pathways - upregulate nucleus raphe magnus
Directly inhibit nociceptive signals at 1st order fibre-dorsal horn neuron synapse
Blunts emotional aspects of pain also
What is the difference between opiate and opioids?
Opioids generally refer to endogenous substances
Opiates refer to exogenous substances
Describe which endogenous opioids target which opioid receptor
Endorphins - mu receptor
Enkephalins - delta receptor
Dynorphins - kappa receptor
What are the effects of opioids?
Analgesia Euphoria Sedation Cough suppression Constipation
Respiratory distress
N&V
Miosis
What is neuropathic pain?
Pain generally caused by neuronal damage
- i.e. anatomical or functional abnormalities of pain pathways
What are the causes of neuronal damage?
Neuropathies, Nerve avulsions, Cancers, Infections, Amputations
MS, Cord injuries, Stroke
What are the mechanisms behind neuropathic pain?
Inflammation => Na+ channel abnormalities - increased expression
Increased sympathetic activity
Sensitisation of dorsal horn neurones
Central sensitisation and reorganisation
Give a common example of neuropathic pain
Trigeminal neuralgia
- usually due to compression of CN V
- results in intense episodic pain
How should neuropathic pain be treated?
With anticonvulsants, e.g.
- carbamazepine
- amitryptilline
- baclofen
- pregabalin/gabapentin
What is phantom limb pain?
Perception of pain in a limb that is no longer there (e.g. has been amputated, congenital absence)
What percentage of amputees does phantom pain occur in?
Up to 80%
What is the best treatment for treating phantom limb pain?
Mirror visual feedback
- mirrors used to trick brain into thinking limb is there by providing visual input suggesting it is
- may provide instant relief
