Temperature And Nociception Flashcards
How do thermal receptors perceive temperature?
Separate receptors for cold to hot
43 degrees is perceived as pain (tissue damaging)
What type of receptors respond to temperature in the skin?
Free nerve endings
What is the minimum temperature not perceived as pain?
15 degrees
What is the maximum temperature not perceived as pain?
43 degrees
What type of thermal receptors are most superficial and are in greater distribution?
Cold receptors
Is the distribution of thermal receptor in the skin uniform or not uniform?
Not uniform
What are the 6 temperature activated transient receptor potential ion channels?
TRPA1 TRPM8 TRPV4 TRPV3 TRPV1 TRPV2
Which temperature activated transient receptor potential ion channels respond to nociceptive stimuli?
TRPA1, TRPV1, TRPV2
Which temperature activated transient receptor potential ion channels respond to heat stimuli?
TRPV1-4
Which temperature activated transient receptor potential ion channels respond to cold stimuli?
TRPM8, TRPA1
Describe the first and second pain.
Early, sharp pain carried by Ad(delta) fibres followed by a later, dull burning pain carried by C-fibres
What are the afferent axon types of free nerve endings in nociception?
Ad(delta) fibre mechano-heat sensitive
C fibre mechano-heat sensitive
What are the characteristics of C-fibres?
Slow conduction
Unmyelinated (thinner)
What are the characteristics of A fibres?
Rapid conduction
Myelinated
What can activate nociceptors?
High intensity and thermal stimuli Chemical stimuli (inflammation)
What are the three modalities mediated by the spinothalamic tract?
Non-discriminative touch
Innocuous temperature sensation
Nociception
What modalities are mediated by Ad(delta) fibres?
Non-discriminative touch
Innocuous temperature sensation
Nociception
What modalities are mediated by C fibres?
Innocuous temperature sensation
Nociception
What activates TRPV1?
Noxious temperatures (>43 degrees) Capsaicin
In what afferent fibres are TRPV1 expressed in?
Both Ad(delta)and C fibres
Describe the pathway of the afferent fibres from when they enter the spinal cord to the formation of spinothalamic tract
Delta and C fibres enter dorsal roots
Passes through Lissauer’s tract (zone) in grey matter
Travel 1-2 levels before entering dorsal horn
Synapse with 2nd order neurons in Rexed’s laminate I-V (anterolateral system)
Ascend spinal cord contra laterally via spinothalamic tract
Which lamina in Rexed’s lamina contains substantia gelatinosa?
Lamina II
What is the relevance of Rexed’s lamina II to temperature and nociception?
It contains substantia gelatinosa which modulates temperature and nociceptive afferents
Decribe the segmental organisation of the spinothalamic tract.
From anterior to lateral
Pressure - touch - pain - temperature
What are the pain pathways for visceral innervation?
Vagus nerve Splanchnic nerves (ganglion)
What type of stimuli do visceral nociceptors respond to?
Stretch
Various chemicals
What type of fibres receive visceral nociceptive stimuli?
C fibres
What are the three categories of pain?
Nociceptive
Inflammatory
Neuropathic
What are the characteristics of nociceptive type pain?
Brief pain
Normal response to acute tissue injury
Stimulus-dependent
Protects by signalling potential tissue damage
Where does the spinothalamic and trigmeniothalamic terminate?
Thalamus ventral posterior nuclei
From where does sensory information terminate in the VPL?
Information from the body
From where does sensory information terminate in the VPM?
Information from the face
Where does the spinothalamic tract project to other than the thalamic VPN?
Reticular formation and parabrachial nucleus
Cingulate and insula cortex
Amygdala and hypothalamus
What are projections of the spinothalamic tract to the Reticular formation and parabrachial nucleus associated with?
Arousal component of pain
What are projections of the spinothalamic tract to the cingulate and insula cortex associated with?
Signalling unpleasant and autonomic components of pain response (respectively)
What are projections of the spinothalamic tract to the amygdala and hympothalamus associated with?
Amygdala: Fear and anxiety response
Hypothalamus: Autonomic response to pain
What are the nerve fibre(s) associated with low intensity, non-noxious stimuli?
Aß fibres
What are the nerve fibre(s) associated with high intensity, noxious stimuli?
Ad(delta) and C fibres
What part of the spinal cord do Aß, delta and C fibres transverse?
Dorsal horn via peripheral nerve and dorsal root ganglion
What are the characteristics of inflammatory type pain?
Active inflammation is present
Spontaneous/stimulus dependent (low and high intensity)
Long term (persistent) but reversible
Protects by producing pain hypersensitivity during healing (peripheral
/central sensitisation)
What are the overall mechanisms/processes involved in inflammatory pain?
Peripheral sensation
Central sensitisation and wind up
Long term potentiation
Describe the process of peripheral sensitisation of nociceptors
Activation/augmentation of nociceptor fibres (by inflammatory mediators eg platelets, bradykinin, histamine)
Release of neuropeptides substance P and Calcitonin Gene-Related Peptide (CGRP)
Causes histamine release from mast cells, vasodilation and plasma extravasation
Histamine decreases threshold for nociceptive activation - hyperalgesia (increased sensitivity of pain)
What does the release of substance P and CGRP cause?
Plasma extravasation
Histamine release
Vasodilation
What process is associated with hyperalgesia?
Histamine release that decreases the threshold for nociceptive activation in peripheral sensitisation
What is central sensitisation?
Enhancement, potentiation or facilitation of synaptic activity in dorsal horn to generate AP’s in 2nd order neurons
What is central sensitisation typically associated with?
Chronic tissue damage/inflammation
What are two possible responses of central sensitisation of nociceptors?
Hyperalgesia: increased pain sensitivity
Allodynia: pain due to stimulus that does not normally provoke pain
Describe the process of wind up and central sensitisation.
Repeated high intensity noxious stimuli
C-fibre stimulation (increased synaptic activity in dorsal horn)
“Wind up”: release of glutamate, substance P and CGRP (neurotransmitters)
Increases duration of post synaptic depolarisation of 2nd order neuron by decreased threshold/increasing sensitivity (summation) and increased receptor fields
Removal of voltage-dependant Mg2+ block from NMDA receptors
Increase influx of Ca2+ triggers long term potentiation/increased release if glutamate
Describe the process of long term potentiation.
Influx of Ca2+ due to opening of NMDAR channels
Enhances glutamate release (protein kinases in post synaptic neuron)
Results in insertion of new AMPA receptors into post synaptic membrane
Increased sensitivity to glutamate
What are the characteristics of neuropathic pain?
Nervous system lesion or disease present
Spontaneous/stimulus dependent (low and high intensity)
Long term (persistent)but reversible
Protects by producing pain hypersensitivity during healing (peripheral
/central sensitisation)
How are pain signal modulated as they travel along sensory pathways?
The gate control theory
Describe the gate-control theory.
Neural gating mechanism
Increased touch/skin mechanoreceptor stimulation (rubbing injured area) - Aß fibres
Increase afferent signals from mechano receptors to dorsal horn
Blockage of noxious afferents (C fibres) at same spinal cord level due to increased touch afferents
Describe the mechanisms of pain modulation by descending pathways?
Somatic sensory cortex sends impulses to the hypothalamus
Hypothalamus stimulates periaqueductal grey matter in brain stem to initiate an analgesic impulse
Analgesic impulse to raphe nucleus in brain stem then down spinal cord in dorsolateral tracts
At spinal cord level, analgesic neurons release endogenous opioids (enkephalins) to inhibit release of substance P from presynaptic neuron and inhibits stimulation of 2nd order neuron (block nociceptive pathway)
Where is the periaqueductal grey matter located?
Brainstem - surrounding cerebral aqueduct in midbrain
What is the function of the periaqueductal grey matter?
Relay/coordination centre for analgesic system (descending pain modulation pathway)
What neurotransmitter is involved in the inhibition (modulation) of nociceptive transmission in the descending pathway.
Endogenous opioids - enkephalin
