Pain Flashcards
loss of pain sensation
due to nerve damage
feature of diabetes mellitus and leprosy
what is pain?
an enigma
differs from classic senses as it is both discriminative sensation and graded motivation
specificity vs convergence
specificity theory - pain is distinct sensation, detected and transmitted by specific receptors and pathways to distinct ‘pain areas’ of brain
convergence theory - pain is integrated, plastic state represented by pattern of convergent somatosensory activity within a distributed network - so called neuromatrix
pain detected by:
nociceptors
free nerve endings
location - widespread in epithelia and connective tissues
classified according to activiating stimulus fibre-type and conduction velocity
- lightly myelinated Adelta fibres - fast, mechano-sensitive, mechanothermal-sensitive
- unmyelinated C fibres - slow, polymodal: mechanical, thermal and chemical
nociceptors respond specifically to pain
a subset of afferents with free nerve endings
most easily demonstrated in heat responses - can find afferents whose activity correlates with pain perception
thermoreceptor activation has already saturated and reached threshold (so we feel it) before nociceptor produces a response
fast pain
or first pain
sharp, immediate
mimicked by stimulation of A delta fibre nociceptors
slow pain
second pain
more delayed
diffuse and longer lasting
mimicked by stimulation of C fibre nociceptors
specificity can be demostrated experimentally by selective blocking the fibres in turn
note - stimulation of A alpha or beta (proprio and mechano) never elicits pain response = distinct set of fibres specifically associated with pain detection
molecular pain receptors
associated with noci nerve endings, activated by heat and chillies
capsaicin receptor - activated in nociceptive A delta and C fibres at 45c and by capsaicin - a vanilloid, active component in chillies
related receptors are activated in A delta fibres alone at even higher thresholds - 52c
respond directly to heat - they are heat detection machines
however, capsaicin is though to mimic endogenous vanilloids released by stressed tissues
therefore they may also work in detecting release of chemicals from stressed and damaged tissues
central pain pathways
complex
2 components:
sensory dicrinimative - signals location, intensity, and type of stimulus
affective-motivational - signals unpleasantness and enables autonomic activation, classic fight or flight
discriminative pathway
involves spinothalamic tract - aka anterolateral system
spinothalamic projections preserve topology
measurement of activity in somatosensory cortex indicates:
- region does respond to stimuli and that response correlates to intensity of pain
- spatially mapped
complex cortical representation of pain
comparison mri of cortical activation by painful (C fibre) or innocuous mechanical (vibration:A beta fibre) stimuli to skin - shows that painful stimuli activate same region on somatosensory cortex as the non painful stimuli applied to same region of skin
however pain activates a distinct response that includes other regions - e.g. activation of insula and singulate cortex
these regions are connected to limbic (emotional) system - part of affective-motivational pathway
affective-motivational pathway
shares some pathways with anterolateral
little/no topology mapping, no projection to cortex instead it goes to cingulate and insula
- neurons in parabrachial nucleus can respond to painful stimuli from anywhere on body surface
number of points of input to limbic and homeostatic systems
strong correlation of painful experience e.g. unpleasantness with activity in cingulate cortex
things that dont match with specificty theory
pain perceived is not always proportional to intensity of stimulus
modulation by other stimuli - acupuncture
phantom limb pain
referral from viscera to skin
placebo effect
hyperalgesia
increased response to painful stimulus
hypersensitivity of damaged skin to normally tolerable painful stimulus
results of lowered nociceptor thresholds which heightens pain response
allodynia
painful response to a normally innocuous stimulus e.g. light brushing of skin with sunburn
inflammatory response - peripheral effects
tissue damage releases a soup of inflammatory substances which affect nerve function, recruit mast cells and neutrophils and increase local blood flow
e.g. bradykinin directly affects function of nociceptive molecular receptors like TRPV1, prostaglandins lower threshold for axon potential generation
some pain killers - analgesics - like aspirin and ibuprofen act on cyclooxygenase, an enzyme important in prostaglandin biosynthesis
central sensitisation
sensitisation can also result from activity dependant local release of substances like prostaglandins from nociceptive dorsal horn neurons
this can lower thresholds for action potential generation, also giving rise to hyperalgesia
another consequnce is that these relay neurons become sensitive to nearby non-nociceptive inputs e.g. mechanoreceptors
= normally innocuous stimuli can be perceived as painful = allodynia
hyperpathia
variant of hyperalgesia and allodynia, but different underlying cause and symptoms
results from fibre/axonal loss/damage (either centrally or peripherally) that raises detection threshold
= when detection threshold is exceeded, subsequent excitability is much greater and patients report an explosive pain
central sensitisation can also occur…..
when central pathways themselves are damaged e.g. in diabetes, shingles, MS and strokes
neuropathic pain is sometimes experienced in phantom limb
phantom limb pain
indicates central representation of body is not passive
children born without limbs can also experience this suggesting central maps may be partly pre-formed
attempts to block pain dont work - pain may also be centrally represented
suggests pain may be a central representation of what we expect pain to be
- does not fit specificity theory
referred pain
pain due to damage in viscera often perceived as coming from specfic areas of skin e.g. heart attack is often preceeded by pain in left shoulder or arm
thought to reflect convergence of visceral afferents onto same pathways as cutaneous afferents in CNS
extremely useful in aiding clinical diagnosis of organ disfunction
central modulation of pain
perception of pain varies according to context
found during WWII, soldiers with severe battle wounds often experienced little/no pain
‘mind over matter’
placebo effect
all suggest mechanisms to overcome even severe pain exist
physiological basis of pain modulation
discovered when experiments stimulating certain regions of midbrain produced pain relief
stimulation of periaqueductal grey activates brainstem nuceli that modulate activity of dorsal horn neurons
in dorsal horn, descending inputs activate enkephalin-releasing interneurons which presynaptically inhibit nociceptive fibres
enkephalins are members of a family of endogenous opiod peptides that also include endorphins and dynorphins
modulation may also occur locally
rubbing an injury can often help pain
thought to be due to local inhibition of mechanoreceptors - A beta fibres of nociceptive C fibre inputs in spinal cord
led to ‘gate’ or ‘sensory interaction’ theory of pain
suggests pain perception to be result of integration of convergent sensory information
existence of such circuits is provocative and challenges assumption of a straight through pain input underlying specificity theory
