Physiology of pain 1 Flashcards
Why do we feel pain?
Warning sign - survival
Avoid harmful situations
Prevents further injury or death
Tells us to rest following an injury
What are the sensations of pain?
Burning Stabbing Sharp Radiating Deep ache Freezing Itch
What are the 3 classifications of pain?
Nociceptive - normal functioning of nociceptors
Inflammatory - pain in response to inflammation
Neuropathic - Pain in response to injury of nervous system
What are nociceptors?
Primary sensory neuron that detects pain
Pseudounipolar - cell body in dorsal root ganglion
From skin, muscle, joints, viscera, meninges to the dorsal horn
How are sensory nerve fibres classified?
By diameter and myelin content
Aalpha and Abetea fibres
Adelta fibres
C fibres
Describe Aalpha and Abeta nerve fibres
Myelinated
large diameter
light touch and proprioception
Describe Adelta fibres
Thinly myelinated
Medium diameter
Light touch, temperature and nociception
Describe C fibres
Unmyelinated
Small diameter
Temperature
Nociceptive
What do meissner’s detect?
Stroking/fluttering
What do pacinicans detect?
Vibration
What do merkel’s discs detect?
Pressure
What do ruffini detect?
Stretch
What does it feel like when Adelta fibre nociceptors respond?
Sharp pricking pain
What does it feel like when C fibre nociceptors respond?
Slow dull ache
Burning pain
Name the peaks found on an electrophysiology recording of the whole sensory neuron
Aalpha Abeta
Adelta
C fibres
Describe the two pain responses
Fast sharp pricking pain - well localised, activation of reflex arcs (Adelta)
Slow dull ache - poorly localised (fibres)
What activates nociceptors?
Pressure
Heat
Cold
Chemical
Tissue damage/inflammation
Which type of pain has no first response?
Visceral pain
What is meant by polymodal nociceptors?
Most C fibres
Respond to pressure, temperature and chemical
Describe the transduction mechanism of pressure
- Mechanically sensitive ion channels
- Not yet identified in eukaryotic cells
Potential channels - acid sensing ion channels, Transient receptor potential family of channels
Describe the transduction mechanism of temperature
- Transient receptor potential family of channels
- Detect different temperatures
Describe the central pain pathway
Pain information ascends the spinothalamic pathway
What is TRPV1?
Vanilloid subtype responds to heat (eg. chilli - capsaicin is and agonist)
Describe the spinothalamic tract
First order neuron - Enter dorsal horn, form tract of lissauer, synapse in substantia gelatinosa (lamina 1 and 2)
Glutamate and substance P excites second order neurons
Second order neurons - Cross in the dorsal horn in each level, ascend in anterolateral column to the thalamus
Third order neurons - Ascend to primary somatosensory cortex - encode the sensory components (tells you where it hurts and modality) Lower body to medial cortex and upper body to lateral cortex. Projections to insula and cingulate cortex. Encodes the emotional components of pain (unpleasantness, negative effect)
What is referred pain?
Convergence of visceral and cutaneous nociceptors on same second order neurons in spinal cord
Brain perceives the pain as cutaneous
Describe the descending regulation of pain
Stress induced analgesia - battle victims with no pain
Higher cortical regions can activate descending modulatory pathways
Name the two important regions in downregulation of pain
Periaqueductal gray matter (PAG)
Rostral ventromedial medulla (RVM)
Cortical regions project to PAG
PAG projects to RVM
RVM projects to dorsal horn
Modulates activity of spinothalamic tract
How is pain inhibited?
PAG neurons excite RVM neurons which inhibit (or excite) the spinothalamic tract
Serotonergic projections act on dorsal horn inhibitory interneurons
Also parallel noradrenalin pathway
Describe the endogenous opioid system
Opioids play an important role in the descending inhibition of pain
(E.g. Endorphins, enkephalins)
Especially stressed-induced analgesia
Opioids are inhibitory
- Act on inhibitory metabotropic receptors
Released from interneurons at multiple sites:
- Midbrain (Periaqueductal gray matter)
- Medulla (Rostral ventromedial medulla)
- Dorsal horn
Name some chemicals released as part of tissue damage in activating or modulating nociceptors
ATP H+ Serotonin/5-HT (from platelets) Histamine (from mast cells) Bradykinin Prostaglandin (conversion of arachidonic acid (lipid) by cyclooxygenase (COX) enzymes) Nerve growth factor
What is the effect of ATP on nociceptors
Binds to the purinergic receptors P2X
Switch on
Cause pain
What is the effect of H+ on nociceptors
Binds to acid sensing ion channels
Switch on
Cause pain
What is the effect of serotonin on nociceptors
Binds to 5HT3 receptors
Switch on
Cause pain
Describe neurogenic inflammation
Activation of one branch of a nociceptor axon, triggers release of substance P and CGRP from another
Causes - Vasodilation, increased permeability, activation of mast cells release of histamine
More inflammation
What can inflammation do to pain?
Cause pain hypersensitivity - pain is more painful
“Pain hypersensitivity after an injury helps healing by ensuring that contact with the injured tissue is minimized until repair is complete”
What is Allodynia?
Non-noxious stimuli produce a painful response
What is Hyperalgesia
Noxious stimuli produce an exaggerated pain response
What are the mechanisms of pain hypersensitivity?
Peripheral sensitisation ( hyperalgesia) Central sensitisation (hyperalgesia and allodynia) - mechanism in neuropathic pain
What is peripheral sensitisation?
Increase in responsiveness of the peripheral ends of nociceptors
Driven by tissue injury or inflammation -
What chemicals are involved in peripheral sensitisation?
bradykinin and NF reduce the threshold of heat activated channels
Prostaglandin reduces threshold of sodium channels
Give a common example of peripheral sensitization
Sunburn
Describe the action of bradykinin
- Binds to receptor (metabotropic – G protein-coupled)
- Activation of protein kinase phosphorylates TRPV1
Phosphorylation of channel reduces its threshold (i.e. it fires more easily)
