Physiology of pain 1 Flashcards
Definition of pain
- Unpleasant sensory experience associated with tissue damage
Classification of pain
Nociceptive - normal functioning of nociceptors
Inflammatory - Pain in response to inflammation
Neuropathic - Pain in response to injury to the nervous system
What are nociceptors
- Are primary sensory neurons that detect pain
Classification of sensory nerve fibres
- alpha and beta fibres
- A delta fibre
- C fibre
Features of alpha and beta fibres
- Myelinated
- Large diameter
- Light touch, proprioception
Features of A delta fibres
- Thinly myelinated
- Medium diameter
- Light touch, temp, nociception
Features of C fibres
- Unmyelinated
- Small diameter
- Temperature, nociception
What does it feel like when alpha delta fibres respond
- Sharp pricking pain
What does it feel like when C fibres respond?
- Slow dull ache
- Burning pain
Features of fast sharp pricking pain
- Well localised
- Activation of reflex arcs
Localisation of slow dull aches
- Poorly localised
Visceral pain and first response
- Visceral pain has no response
What activates nociceptors
- Pressure
- Heat
- Cold
- Chemical
- Tissue damage/inflammation
What is polymodality
- Polymodality is the feature of a single receptor of responding to multiple modalities, such as free nerve endings which can respond to temperature, mechanical stimuli (touch, pressure, stretch) or pain (nociception)
- Most C-fibre nociceptors are polymodal
How is pressure detected
- Mechanically sensitive ion channels
- Not yet identified in eukaryotic cells
- Acid sensing ion channels
- Transient receptor potential(TRP) family of channels
How is temperature detected
- Transient receptor potential family of channels
- Detect different temperatures
Which tract does pain information ascend via
- Spinothalamic tract
Where do first-order neurons enter and synapse in spinothalamic tract
- Enter dorsal horn
- Form tract of lissauer
- Synapse in substantia gelatinosa
Path of second-order neurons in spinothalamic tract
- Cross in dorsal horn at each level
- Ascend in anterolateral column to thalamus
How do we feel referred pain
- Convergence of visceral and cutaneous nociceptors on same second order neurons in spinal cord
- Brain perceives pain as cutaneous
Referred pain for angina
- Angina perceived as pain in upper chest wall and left arm
Path of third-order neurons in spinothalamic tract
- Ascend to primary somatosensory cortex
- Projections to insula and cingulate cortex
- Encode the emotional components of pain(unpleasantness, negative-affect)
What regions of the brain are activated in the pain network
- Many cortical regions activated(including limbic system, prefrontal cortex)
What are the two important regions of the descending regulation pathway of pain
- Periaqueductal gray matter(PAG)
- Rostral ventromedial medulla(RVM)
Purpose of the descending regulation of pain pathway
- Modulates activity of spinothalamic tract
How is pain inhibited by the action of the descending regulation of pain pathway
- Cortical regions project to PAG
- PAG projects to RVM
- RVM projects to dorsal horn
- PAG neurons excite RVM neurons, which inhibit(or excite) the spinothalamic tract
Where do serotonergic projections act in the descending pain regulation pathway
- Act on dorsal horn inhibitory interneurons
Role of opioids in the descending inhibition of pain
- Opiods are inhibitory
- Act on inhibitory metabotropic receptors
Where are opioids released
Released from interneurons at multiple sites
- Midbrain(Periaqueductal gray matter)
- Medulla(Rostral ventromedial medulla)
- Dorsal horn
Effect of ATP on nociceptors
- ATP binds to purinergic receptors(P2X)
Effect of H+ on nociceptors
- Activates acid-sensing ion channels by binding to them
Effect of serotonin on nociceptors
- Binds to 5-HT3 receptors(activation)
What does switching nociceptors cause and give an example
- Switch on = PAIN
- In runners, lactic acid build up leads to tissue acidosis(increase in protons) = activation of nociceptors = PAIN
What is neurogenic inflammation
- Inflammation arising from the local release by afferent neurons of inflammatory mediators
Process of neurogenic inflammation
- Activation of one branch of a nociceptor axon, triggers release of substance P and CGRP from another(leads to cascade)
- Release of histamine causes more inflammation
Causes of histamine release in neurogenic inflammation
- Vasodilation
- Increased permeability
- Activation of mast cells
What is an effect of inflammation that helps with repair
- Inflammation can cause pain hypersensitivity
- Helps after an injury as it ensures 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 is peripheral sensitization
- Increase in responsiveness of the peripheral ends of nociceptors
What is peripheral sensitisation driven by
- Driven by tissue injury or inflammation
- Bradykinin and NGF reduce the threshold of heat activated channels(TRPV1)
- Prostaglandin reduces the thresholds of sodium channels
Common example of peripheral sensitisation
- Sunburn
Mechanism of action - TRPV1
Bradykinin
- Binds to receptor(metabotropic - G protein-coupled)
- Activation of protein kinase phosphorylates TRPV1
- Phosphorylation of channel reduces its threshold(ie it fires more easily)
TRPV1 agonist and temp
- Chilli(capsaicin)
- HOT
TRPM agonist and temp
- Menthol
- Cold
TRPA1 agonist and temp
- Cinnamon
- V Cold
What do first order neurons in the spinothalamic tract release to excite second-order neurons
- Glutamate and substance P to excite second-order neurons
Cortex for lower body projections in spinothalamic tract
- Medial somatosensory cortex
Cortex for upper body projections in spinothalamic tract
- Lateral somatosensory cortex
How does descending regulation of pain occur
- Stress-induced analgesia
- eg: battle victims with no pain
Inhibition of pain pathway from RVM to dorsal horn
RVM –serotonergic neuron –> inhibitory interneuron –> nociceptor in dorsal horn
