Physiology of pain 1 Flashcards
Classifications of pain [3]
Nociceptive
- Due to functioning nociceptors
Inflammatory
- Due to response to inflammation
Neuropathic
- Response to injury of the nervous system
Nociceptors
- Definition
- Function
Primary sensory neurones that detect pain from
- Skin
- Muscles
- Joints
- Viscera
- Meninges
Carry sensory information to dorsal root ganglia —> dorsal horn
Contains free nerve endings in the periphery [A-delta or C fibres]
A-alpha and A-beta sensory fibres
- Myelination
- Function
- Diameter
- Conduction velocity
Myelinated afferent nerve fibre
- Detects light touch and proprioception
- Large diameter
- 30-75 m/sec
A-delta sensory fibres
- Myelination
- Function
- Diameter
- Conduction velocity
- Response to pain
Thinly myelinated afferent fibres
- Detects light touch, temperature and nociception
- Medium diameter
- 5-30 m/sec
Response to pain
- Sharp, prickling
C fibres
- Myelination
- Function
- Diameter
- Conduction velocity
- Response to pain
Unmyelinated afferent nerve fibre
- Detects temperature and pain [nociception]
- Small diameter
- 0.5-2 m/sec
Response to pain
- Slow, dull ache
- Burning
Meissner’s fibres
- Type of fibre
- Function
- Location
A-beta fibres
Detects stoking and fluttering
Found in glabrous skin
Pacinian fibres
- Type of fibre
- Function
- Location
A-beta fibres
Detects vibration, deep in glabrous skin
Merkel disc
- Type of fibre
- Function
- Location
A-beta fibres
Detects pressure in glabrous skin
Ruffini fibres
- Type of fibre
- Function
- Location
A-beta fibres
Detects stretch in hairy skin
Pain transduction
- Types of pain
- Fast sharp pricking
- Localised
- Activates reflex arcs
- Not present in visceral pain - Slow dull ache
- Poorly localised
Factors that activate nociceptors [4]
Pressure
Heat/ cold [temperature]
Chemical
Tissue damage/ inflammation
Polymodal nociceptors
Responds to different types of sensory stimuli
- Pressure
- Temperature
- Chemical
Most C-fibres nociceptors are polymodal
Pressure transduction
Mechanically sensitive ion channels
Specific channel still not known.
Acid sensing ion channels and TRPA1 are involved
Temperature transduction
Transient receptor potential family of channels
TRPV1- detects hot temperature
TRPM- detects cold temperature
TRPA 1- Detects very cold temperatures
Agonists for
- TRPVI
- TRPM
- TRPA1
TRPV 1
- Chilli [capsaicin]
TRPM
- Menthol
TRPA 1
- Cinnamon
Central pain pathway
Ascends spinothalamic tract
First order neurones
- Enter dorsal horn via tract of Lissauer
- Synapse in substantia gelatinosa [lamina 1 + 2] with second order neurones
- Release glutamate and substance p
Second order:
- Crosses the dorsal horn at each level
- Ascends anterolateral column to thalamus
Third order:
- Projection into somatosensory cortex
- Projection into insula and cingulate cortex
- Activation of cortical regions [e.g limbic, prefrontal]
Referred pain
Brain perceiving visceral pain as cutaneous
- Visceral and cutaneous nociceptors converge on the same second order neurones
Sensory homunculus
The distribution of sensation in the somatosensory cortex
Lower body= medial cortex
Upper body= lateral cortex
Spinothalmic tract projection in the somatosensory cortex
Encodes the sensory components
- Location of pain
- Modality of pain
Spinothalmic tract projection in insula and cingulate cortex
Encodes the emotional components of pain
Descending modulatory pathways
Modulation of spinothalamic tract activity, originating from the cortex
Cortex—-> Periaqueductal grey matter [midbrain]
Periaqueductal grey matter—-> Rostral ventromedial medulla [medulla]
Inhibition of pain
Periaqueductal grey matter [PGM] excites rostral ventromedial medulla {RVM]
- Inhibits the spinothalamic tract
Serotonergic projection from RVM synapses onto inhibitory neurone in dorsal horn
NADR pathway is also parallel to this
Endogenous opioid system
Act on inhibitory metabotrophic receptors
- Important in stress induced analgesia
Release site = from interneurones
- Periaqueductal grey matter [midbrain]
- Rostal ventromedial medulla [medulla]
- Dorsal horn
Chemicals that activate or modulate nociceptors in inflammatory pain [7]
ATP
H+
Serotonin/ 5-HT
Histamine
Bradykinin
Prostaglandin
Nerve growth factor
ATP activation of nociceptors
Binds to purinergic receptors [P2X]
H+ activation of nociceptors
Binds to acid-sensing ion channels
Serotonin activation of nociceptors
Binds to 5-HT3 receptors
Neurogenic inflammation
Activation of a branch of nociceptor axon = release of substance P and CGRP from another branch.
Release of the pro- inflammatory chemicals=
- Vasodilation
- Increased permeability
- Activation of mast cells= release of histamines= more inflammation
Pain hypersensitivity
Can occur as a result of inflammation
- Pain stimulus is perceived as more painful.
Examples:
- Allodynia
- Hyperalgesia
Allodynia
Type of pain hypersensitivity
- Painful response to non-noxious stimuli
Hyperalgesia
Typer of pain hypersensitivity
- Exaggerated pain response to noxious stimuli
Peripheral sensitisation
- Mechanism
- Chemicals released
- Examples
Mechanism for hyperalgesia
Inflammation/tissue damage = Increase in responsiveness of the peripheral ends of nociceptors
Release of:
- Bradykinin and NGF = reduction of threshold for TRPV-1
- Prostaglandin = reduction of threshold of Na+ channels.
Example: after sunburn
Bradykinin
- peripheral sensitisation
Activates TRPV-1
- Binds to metabotrophic G-protein
- Activates protein kinase —–> phosphorylates TRPV1 = reduction of threshold for channel]
