T2L7 physiology of pain I Flashcards
pain is
an unpleasant sensation associated with tissue damage
accompanied by emotional reaction eg fear/ anger/anxiety
3 types of pain
- nociceptive
- inflammatory
- neuropathic
- nociceptive
normal functioning of nociceptors
- nociceptors are primary sensory neurons that detect pain:
skin/muscles/meninges/joints/viscera V dorsal root ganglia cell body V dorsal horn
nociceptors have free nerve endings in periphery (See s9)
sensory fibre classifications
Aα and Aβ fibres: 100m/s
- myelinated
- large diameter
- light touch and proprioception
Aδ (delta) fibres: 30m/s
- thinly myelinated
- medium diameter
- light touch, temperature, nociception
- sharp, pricking pain - well localised (reflex arc activation)
C fibre: 1m/s
- unmyelinated
- small diameter
- temperature and nociception
- dull ache/ burning pain - poorly localised
- polymodal usually
ie pain is Aδ and C
activated by:
- pressure
- heat
- cold
- chemical
- tissue damage
- inflammation
polymodal- respond to pressure, temperature and chemical. to distinguish there must be decoding within cns
pain transduction
2 pain responses:
the initial fast sharp pricking pain followed by slow dull ache ( s 12)
visceral pain has no first response
polymodal
polymodal- respond to pressure, temperature and chemical
pain transduction mechanisms
pressure:
- mechanically sensitive ion channels
temperature:
- transient receptor potential channels
- different types detect different temsp
central pain pathways
pain info ascends spinothalamic tract
first order neurons:
- enter dorsal horn
- form tract of Lissauer
- synapse in subsantia gelatinosa
spinothalamic tract
second order neurons:
- cross in dorsal horn at each level
- ascend into anterolateral column to thalamus
- s18
third order neurons: - encodes the sensory components- location & modality - ascend to primary somatosensory cortex - lower body > medial cortex - upper body > lateral cortex = sensory homunculus
- projections to insula and cingulate cortex encode emotional response to pain
referred pain
- convergence of visceral and cutaneous nociceptors on same second order neurons in spinal chord
- brain perceived pain as cutaneous
eg angina perceived as pain in upper chest wall and left arm, as the nociceptors from heart and cutaneous ones from these areas synapse together
descending regulation of pain
eg when you get stabbed and don’t feel it:
- stress induced analgesia
the pain experience is determined by many factors eg emotion, past experience, behaviour
higher cortical regions can activate descending modulatory pathways
2 important regions:
- periaqueductal grey matter (PAG)
- rostral ventromedial medulla (RVM)
cortical regions > PAG > RVM > dorsal horn
- modulated spinothalamic tract
pain inhibition:
PAG neurons excite RVM neurons which inhibit the spinothalamic tract (serotonergic neurons act on dorsal horn inhibitory interneurons)
endogenous opioid system
- descending inhibition of pain
- eg endorphins
stress induced analgesia
released from interneurons at multiple sites:
- midbrain
- medulla
- dorsal horn
- inflammatory
hyperalgesia and allodynia
- causes pain hypersensitivity to make healing easier
allodynia- non noxious stimuli produce painful response
hyperalgesia- noxious stimuli produce exaggerated pain response
mechanisms of pain hypersensitivity:
- hyperalgesia- peripheral sensitization
- hyperalgesia and allodynia - central sensitization
s 31
peripheral sensitization:
- increase responsiveness to peripheral ends of nociceptors
- driven by injury or inflammation eg sunburn
- Bradykinin and NGF reduce the threshold of heat activated channels (TRPV1)
- Prostaglandin reduces the thresholds of sodium channels
bradykinin binds to metabotropic g protein receptor
- activates protein kinase
- phosphorylates TRPV1
chemicals released from tissue damage that modulate or activate nociceptors
ATP (binds to purinergic receptors - direct)
H+ (binds to acid sensing ion channels - direct)
5-HT (binds to 5-HT3 receptors- direct)
these activate nociceptors»_space; pain
eg in runners acid buildup > pain
histamine
bradykinin
prostaglandin
nerve growth factor
neurogenic inflammation
Activation of one branch of a nociceptor axon, triggers release of substance P and CGRP from another
causes:
- vasodilation
- increase permeability
- activation of mast cells
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