Physiology of Pain Flashcards
General pain pathway (three orders of neurons)
- First Order neurons
- Cell bodies within the dorsal root ganglion (in the spinal cord)
- One axon splits into two branches, a peripheral branch (extending towards the peripheries), and a central branch extending centrally into the spinal cord/brainstem - Second order neurons
- Cell bodies found in the rexed laminae of the spinal cord/nuclei of the cranial nerves
- Then cross in the anterior white matter of the cord
- Ascend cranially in the spinothalamic tract to the ventral posterolateral (VPL) nucleus of the thalamus - Third order neurons
- Lie within the ventral posterolateral (VPL) of the thalamus
- Project via the posterior limb of the internal capsule to terminate in the primary somatosensory cortex (postcentral gyrus)
Nociceptors
Nociceptors
- Exist at the free nerve endings of the primary afferent neurons
- Has its own receptive field (size varies, may be overlap)
Types:
- Mechanical (stretch, pressure, with sharp, pricking pain)
- Chemical (exogenous/endogenous chemical agents, such as prostanoids, histamines, etc.)
- Thermal (thermal sensations - slow/burning pain, cold/sharp pain)
- Polymodal - detect mechanical, chemical, and thermal stimuli
Transmission to the spinal cord
Initial signal: A-delta nerve fibres
- Signals from nociceptors transmitted to the dorsal horn via A-delta nerve fibres
- A-delta nerve fibres have low threshold for firing and fast conduction speed (transmit first pain felt)
- Permit localisation of pain and form the afferent pathway for reflexes elicited by pain
- Terminate in the rexed laminae where they release glutamate
Polymodal nociceptors: C fibres
- unmyelinated, slower conduction speed
- Responsible for secondary pain - often dull, deep, throbbing in nature
- Large receptive fields, poor localisation
- High threshold for firing but noxious stimuli can cause sensitisation and reduce threshold for firing
- Terminate in the rexed leminae II and release substance P
- Significant in visceral pain
Chemical mediators of pain
Factors released upon tissue damage the lead to the activation of nociceptors
Include:
- Arachidonic acid
- Potassium
- 5-HT
- Histamine
- Bradykinin
- Lactic acid
- Adenosine
- Prostaglandin
- Nor adrenaline
Pathophysiology of neurogenic inflammation
Activation of peripheral afferents may result in neuromodulator release from nearby peripheral branches, including substance P, neuropeptide Y, ATP, glutamate
- Can act on peripheral blood vessels, mast cells, and sympathetic nerve fibres to cause vasodilation, vascular permeability, and plasma extravasation
Descending modulation of pain
- Opioid receptors regulate the neurotransmission of pain signals
- Activation leads to a reduction in neurotransmitter release and cell hyperpolarisation
Endogenous opioids act on receptors to reduce neurotransmitter release from the first order neuron, then hyperpolarises the second-order neuron
Overall, reduces the firing of action potentials in the second-order neuron
Endogenous opioids and receptors
B-endorphins (bind to mu opioid receptors)
Dynorphins (bind to kappa opioid receptors)
Enkephalins (bind to delta opioid receptors)
Central sensitization of pain
‘Wind up’
- NMDA receptor is an ion channel normally blocked by a magnesium ion
- After prolonged peripheral C-fibre nociceptive drive, increased presynaptic release of neurotransmitters causes depolarization of the post synaptic neurons via actions on AMP and NK1 receptors
- Also allows the release of the magnesium ion blocking the pore of the NMDA receptor
- Calcium then flows through and increases postsynaptic excitability, ultimately leading to potentiation of the postsynaptic response
Visceral pain: receptor types
Visceral nociceptors are thought to be polymodal (c fibres)
- Mechanosensory (responding to a range of distention pressures, including tonic/normal, high distention, and inflammation). Located in the walls and muscles of internal organs
- Chemoreceptors (located in the mucosa and muscular layers)
- Thermoreceptors (located in the mucosa and muscular layers)
Visceral pain: Innervation
Innervation:
- Predominantly unmyelinated C fibres, some thinly myelinated A fibres
- Afferent nerves that run parallel with the efferent autonomic nerves comprising the sympathetic and parasympathetic systems
- Unlikely peripheral afferent fibres, visceral input has a wide spread through the spinal cord and may project to other segments and contralateral tracts
- Functionally, the vast majority of visceral sensations do not reach consciousness
Common mediators of cancer pain
- Inflammatory signalling mechanisms related to tissue injury by cancer
Chronic cancer pain:
- Typically prolonged firing of nociceptive C fibres (polymodal nociceptors)
Basics of pain transmission
- Stimulation to nociceptors (polymodal C fibres, or A delta nerve fibres)
- Travel to spinal cord (rexed laminae), where first-degree sensory neurons synapse
- Central pathways (spinothalamic tract) carry nociceptive signalling to contralateral thalamus (ventral posterolateral nucleus) and pain is first perceived
- Thalamic fibres then project pain information to eery lobe of the brain
