pain Flashcards
allodynia
sensitisation to normally innocuous stimulu
specificity theory
pain is a distinct sensation
detected and transited by specific recpetors and pathways to distinct pain areas of the brain
convergence theory
pain is an integrated plastic state represented by a pattern of convergent somatosensory activity within a distributed network (neuromatrix)
A delta fibres
lightly myelinated Fast (relative) about 20 m/s
mechano-sensitive
mechano-thermal sensitive
C fibres
unmyelinated SLOW about 2 m/s
polymodal: mechanical, thermal and chemical
types of free nerve endings
Although mechanoreceptors, thermoreceptors, and nociceptors are all examples of free endings, nociceptors are the most common type.
free nerve endings location and modality
location: widepsread in epithelia and connective tissues
modality: pain, heat, cold
thermoreceptor response to pain
is specific
i.e. can find afferents whose activity correlates with pain perception
it can be clearly shown with heat response that thermo-receptor activation has already started before pain is perceived by nociceptor
fast or ‘first’ pain
sharp and immediate
can be mimicked by direct stimulation of A delta fibre nociceptors
slow or ‘second’ pain
more delayed, diffuse and longer lasting
mimicked by stimulation of C fibre nociceptors
activation of which types of receptors never elicits pain sensation
stimulation of A alpha and A beta (proprioceptive and mechanoceptive) fibres
distinct set of A delta and C fibres specifically associated with pain detection
molecular pain receptors activated in nociceptive A delta and C fibres at 45 oC
the capsaicin receptors (TRPV1)
the vanilliod, capsaicin is also active component in chillies
TRP
Transient receptor potential proteins
nociceptors can detect release of chemicals
capsaicin is thought to mimic endogenous vanilloids released by stressed tissues so nociceptors may also work by detecting release of chemicals from stressed cells
sensory discrimation pathway of nocipetive info to the brain
signals location, intensity and type of stimulus
used the spinothamalmic tract
affective-motivational pathwah of nociceptive info to the brain
singals unpleasantness and enables autonomic activation, flight or fight response
spinothalamic tract//anterolateral system
major skin to thalamus sensory pathway
transmits signals from receptors ending via dorsal root ganglion cells via spinal cord, medulla and midbrain to thalamus
MRIs can show representation of pain
activation of C fibres or A beta fibres shows same area of somatosensory cortex activation for both non painful mechanical stimuli and painful ones
but pain also activates a distinct response that includes other regions
e.g. insula and cingulate cortex
activation of insula and cingulate cortex
connected to the limbic system and regulate emotional responses
so part of the affective-motivational response to pain
affective motivational pathways
- shares some paths with spinthalamic pathway
- little or no topographic mapping (neutrons from parabrachial nucleus can respond to painful stimuli from anywhere on the body’s surface)
- number of points of input to the emotional (limbic) and homeostatic (hypothalamic) system
- strong correlation of painful experience (unpleasantness) with activation in cingulate cortex
affective motivational pathway points
information from upper body via spinal cord caudal medulla middle medulla-- reticular formation-- hypothalamus and limbic system mid pons parabrachial nucleus projections to the amygdala and hypothalamus thalamus insula cingulate cortex
phenomena that don’t fit with the theories of specificity
pain perceived not always proportional to intensity of stimulus
modulation of pain by other stimulus (acupuncture)
perception of pain in severed limbs (phantom)
referral of pain from viscera to skin (heart attack)
placebo effect
hyperalgesia (sensitisation)
increased response to a painful stimulus
e.g.hypersensitivity of damaged skin to a normally tolerable painful stimulus (e.g. light skin prick)
a result of lowered nociceptor thresholds which heightens pain response
allodynia (sensitisation)
painful response to a normally innocuous stimulus
e.g. painful sensitivity of sunburnt skin to gentle mechanical stimulus (e.g. light brushing) or mild temp
inflammatory response peripheral effects of tissue damage
tissue damage releases inflammatory substances which affect nerve function, recruit mast cells and neutrophils and increase local blood flow
e.g. bradykinin directly affects the function of nociceptive molecular receptors such as TRPV1
pain relief
aspirin and ibuprofen act on cyclooxygenase (COX) an enzyme for prostaglandin biosynthesis
dorsal horn
The posterior grey column (posterior cornu, dorsal horn, spinal dorsal horn posterior horn) of the spinal cord is one of the three grey columns of the spinal cord. It receives several types of sensory information from the body, including fine touch, proprioception, and vibration.
release of prostaglandins from nociceptive dorsal horn neurons results in what
a lowering of the thresholds for action potential generation for neurones relaying nococpetive info – giving rise to hyperalgesia
another consequence is that these neutrons become sensitive to non nociceptive inputs- allodynia (non painful perceived as painful)
because release of prostaglandins in dorsal horn affect thermal and mechanic receptors (the non pain fibres)
hyperpathia
a variant of hyperalgesia and allodynia (different underlying causes)
when there is axonal loss (centrally or peripherally) results in raising of the detection threshold (i.e. need greater stimulation to detect stimulus)
but when the detection is felt the pain is explosive!!
central sensitisation in diseases
can occur when the central pathways themselves are damaged e.g. in diabetes, shingles, MS and after a stroke
the virus of shingles sits latent in nerves
what is suggested by the phenomenon of phatom limb pain
indicates central representation of the body is not passive
it persists in the absence of peripheral input
children born without limbs still get phantoms suggesting the brain’s map of the body may be pre- formed
phatom limb pain is hard to control suggesting that the pain is also centrally represented
NOT fitting with specificity theory
referred pain
pain due to damage in the viscera (gut) is often perceived as coming from specific locations in the skin according to what organ is affected e.g. heart attack- pain in left shoulder and arm
(not easily explained by specificity theory)
why do we get referred pain
thought to reflect convergence of visceral afferent onto the asme pathways as cutaneous afferents in CNS
useful in aiding clinical diagnosis of organ dysfunction!
central modulation of pain
mind of matter - when walking through fire
Henry Beecher - soldifers in WW2 with severe wounds often felt no or little pain
mere suggestion that pain will be controlled by pain relief creates ‘placebo effect’
physiological basis of pain modulation
experiemnts stimlating regions of the midbrain produced pain relief
e.g. the periaquecductal grey activates brainstem nuclei that modulate activity of dorsal horn neutrons
in the dorsal horn, descending inputs activate enkephalin-relseaing interneurons which presynaptically inhibit nociceptive fibres
enkephalins
members of a family of endogenous opioid peptides that also include endorphins and dynorphins
interneurons that release encephalon presynaptically inhibit nociceptive fibres
local modulation of pain
rubbing an injury often reeves pain
thought to be due due local inhibit by mechanoreceptors (Adelta fibres) of conceptive (C fibres) inputs in the spinal cord
Melzack and Wall (1965)– proposed ‘gate’ or ‘sensory interaction’ theory of pain
suggested pain perception to be the result of integration of convergent sensory info
again challenges the assumptions of a straight through pain input of specificity theory
we know that pain is not due to ramping up of normal thermo-receors in part because…?
thermoreceptor firing is saturated by the time pain is perceived in response to heat
