Physiology of pain 1 Flashcards Preview

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1

Classifications of pain [3]

Nociceptive
- Due to functioning nociceptors

Inflammatory
- Due to response to inflammation

Neuropathic
- Response to injury of the nervous system

2

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]

3

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

4

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

5

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

6

Meissner's fibres
- Type of fibre
- Function
- Location

A-beta fibres

Detects stoking and fluttering

Found in glabrous skin

7

Pacinian fibres
- Type of fibre
- Function
- Location

A-beta fibres

Detects vibration, deep in glabrous skin

8

Merkel disc
- Type of fibre
- Function
- Location

A-beta fibres

Detects pressure in glabrous skin

9

Ruffini fibres
- Type of fibre
- Function
- Location

A-beta fibres

Detects stretch in hairy skin

10

Pain transduction
- Types of pain

1. Fast sharp pricking
- Localised
- Activates reflex arcs
- Not present in visceral pain

2. Slow dull ache
- Poorly localised

11

Factors that activate nociceptors [4]

Pressure

Heat/ cold [temperature]

Chemical

Tissue damage/ inflammation

12

Polymodal nociceptors

Responds to different types of sensory stimuli
- Pressure
- Temperature
- Chemical

Most C-fibres nociceptors are polymodal

13

Pressure transduction

Mechanically sensitive ion channels

Specific channel still not known.

Acid sensing ion channels and TRPA1 are involved

14

Temperature transduction

Transient receptor potential family of channels

TRPV1- detects hot temperature

TRPM- detects cold temperature

TRPA 1- Detects very cold temperatures

15

Agonists for
- TRPVI
- TRPM
- TRPA1

TRPV 1
- Chilli [capsaicin]

TRPM
- Menthol

TRPA 1
- Cinnamon

16

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]

17

Referred pain

Brain perceiving visceral pain as cutaneous
- Visceral and cutaneous nociceptors converge on the same second order neurones

18

Sensory homunculus

The distribution of sensation in the somatosensory cortex

Lower body= medial cortex

Upper body= lateral cortex

19

Spinothalmic tract projection in the somatosensory cortex

Encodes the sensory components
- Location of pain
- Modality of pain

20

Spinothalmic tract projection in insula and cingulate cortex

Encodes the emotional components of pain

21

Descending modulatory pathways

Modulation of spinothalamic tract activity, originating from the cortex

Cortex----> Periaqueductal grey matter [midbrain]

Periaqueductal grey matter----> Rostral ventromedial medulla [medulla]

22

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

23

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

24

Chemicals that activate or modulate nociceptors in inflammatory pain [7]

ATP

H+

Serotonin/ 5-HT

Histamine

Bradykinin

Prostaglandin

Nerve growth factor

25

ATP activation of nociceptors

Binds to purinergic receptors [P2X]

26

H+ activation of nociceptors

Binds to acid-sensing ion channels

27

Serotonin activation of nociceptors

Binds to 5-HT3 receptors

28

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

29

Pain hypersensitivity

Can occur as a result of inflammation
- Pain stimulus is perceived as more painful.


Examples:
- Allodynia
- Hyperalgesia

30

Allodynia

Type of pain hypersensitivity
- Painful response to non-noxious stimuli

31

Hyperalgesia

Typer of pain hypersensitivity
- Exaggerated pain response to noxious stimuli

32

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

33

Bradykinin
- peripheral sensitisation

Activates TRPV-1
- Binds to metabotrophic G-protein

- Activates protein kinase -----> phosphorylates TRPV1 = reduction of threshold for channel]