Pain Flashcards
How are the different types of pain categorised?
Usually by the area of the body the pain signals originate from
Where does somatic pain originate?
Cutaneous, skeletal muscle/tissue or the peritoneal membrane
When would somatic pain arise?
Post-operative
Post-exercise
Mild trauma
Where does visceral pain originate from?
Thoracic or abdominal organs
When would visceral pain arise?
Post-operative
Cancer
Traumatic injury
Where does neuropathic pain originate from?
Specific damage to nerves
When would visceral pain arise?
Amputation
Type 2 diabetes, hyperglycaemia induced damaged
Where does sympathetically maintained pain originate from?
Sensitisation of the CNS causes neuropathic pain in distribution of a sympathetic nerves
When would sympathetically maintained pain arise?
Complex regional pain syndromes
Describe the differences between nociception and pain.
Nociception refers to the central nervous system (CNS) and peripheral nervous system (PNS) processing of noxious stimuli, such as tissue injury and temperature extremes, which activate nociceptors and their pathways.
Pain is the subjective experience one feels as a result of the activation of these pathways but is also influenced by psychological factors such as past experiences, beliefs about pain, fear or anxiety.
What are nociceptors?
They are the specialised endings of primary afferent nerve endings of Alpha-delta and C fibres within the periphery. They detect noxious stimuli, transforming the stimuli into electrical signals, which are then conducted to the central nervous system.
Where are nociceptors found?
In mammals, nociceptors are found in any area of the body that can sense noxious stimuli. External nociceptors are found in tissue such as the skin (cutaneous nociceptors), the corneas, and the mucosa. Internal nociceptors are found in a variety of organs, such as the muscles, the joints, the bladder, the visceral organs, and the digestive tract.
Where are the cell bodies of nociceptors found?
Either in the dorsal root ganglia or the trigeminal ganglia. The trigeminal ganglia are specialized nerves for the face, whereas the dorsal root ganglia are associated with the rest of the body.
What are the different types of noxious stimuli?
Mechanical
Thermal
Polymodal
What are AB fibres responsible for?
They are primary afferent nerve fibres that respond to/transmit non-noxious stimuli. Essentially carry information related to touch.
Describe the characteristics of AB fibres.
Aβ fibres are highly myelinated and of large diameter, therefore allowing rapid signal conduction. They have a low activation threshold and usually respond to light touch and transmit nonnoxious stimuli.
Describe the characteristics of Aδ fibres.
Aδ fibres are lightly myelinated and smaller diameter, and hence conduct more slowly than Aβ fibres. They respond to mechanical and thermal stimuli. They carry rapid, sharp pain and are responsible for the initial reflex response to acute pain.
Describe the characteristics of C-fibres.
C fibres are unmyelinated and are also the smallest type of primary afferent fibre. Hence they demonstrate the slowest conduction. C fibres are polymodal, responding to chemical, mechanical and thermal stimuli. C fibre activation leads to slow, burning pain.
Describe the different types of pain that Aδ fibres and C-fibres are responsible for transmitting.
Both Aδ fibres and C-fibres are responsible for responding to noxious stimuli. Aδ fibres are found commonly in skin are respond to mechanical and thermal stimuli. They are responsible for sharp, pricking pain that is first experienced with an injury. Whereas C-fibres which have a slower transmission are associated with the longer lasting, aching dull pain which persists for longer.
Describe how the first and second pain mediated by the different fibres gives rise to different behaviours?
The first pain experienced mediated by Aδ fibres is said to be very informative, as a reflex action it encourages us to move away from danger. Whereas the persisting, longer-lasting pain mediated by the C-fibre drives overall behaviour change.
What are the four processes of nociception?
Detection - noxious stimuli activate nociceptive fibres
Transmission - how the signal transmits to the brain
Perception - how the brain perceives signals
Modulation - how can pain signals be changed
How do nociceptors become activated?
Any tissue damage results in the initiation of an inflammatory response. Inflammatory mediators are released from damaged tissue and can stimulate nociceptors
directly. They can also act to reduce the activation threshold of nociceptors so
that the stimulation required to cause activation is less. This process is called
primary sensitisation.
What are some examples of inflammatory mediators that can directly activate nociceptors?
Bradykinin, serotonin, prostaglandins, cytokines and H+
When nociceptors become activated what can be released?
When activated nociceptor fibres can release substance P, neuropeptides, CGRP, NGF and Neuropeptide Y which can then act on surrounding cells including immune cells and blood vessels.
What are the effects of these mediators in terms of peripheral modulation?
These then cause the release of inflammatory mediators (in a positive feedback loop) and nerve growth factor which then increases the sensitivity of the neurons.
What is hyperalgesia?
Sustained release can therefore cause increased sensitivity to pain.
How do nociceptor fibres become activated?
When these inflammatory mediators act either on the ion channels or on the GPCRs and the nociceptor fibres become sensitised, once the depolarisation becomes above the threshold firing of action potential occurs which is then transmitted to the spinal cord.
State the ion channels present on the nociceptive afferent terminal and how they are stimulated?
ASIC ion channels which respond to high H+ concentrations
PX2 ion channels which respond to high levels of ATP
TRPV1 which respond to an acidic pH (below 5.5), noxious heat (become activated at 43 degrees), capsaicin, endogenous chemicals such as Endovanilloids
Voltage gated sodium channels
Voltage gated potassium channels
What is the downstream effects of ASIC, PX2 and TRPV1 activation?
All are cation selective ion channels, which when activated cause influx of cations such as calcium and sodium which drives depolarisation. This leads to the opening of the voltage gated sodium channels also present inducing the firing of action potential when it reaches above the threshold.
State the GPCRs present on the nociceptive afferent terminal and what are their ligands.
B2 receptor which respond to bradykinin, an inflammatory mediator
Prostanoid or EP receptor which responds to prostaglandins
An inhibitory GPCR which responds to opioids, cannabinoids and Noradrenaline
Describe the downstream signalling pathway of B2 activation.
B2 activation upon binding to bradykinin activates PKC which then induces phosphorylation of TRPV1 - which induces its sensitisation and causing it to open and enhances depolarisation, by then causing calcium and sodium influx.
Describe the downstream signalling pathway of Prostanoid/EP receptor activation.
Bradykinin induces release of prostaglandins which then act on the GPCR causing the stimulation of PKA and the phosphorylation of of many ion channels such as voltage gated sodium channels then causing depolarisation. EP receptor stimulation also prevent opening of the K+ channels which would cause hyperpolarisation and therefore allow it to more closely reach threshold for action potential firing.
How do inhibitory GPCRs work?
Their downstream signalling pathway induces the opening of K+ ions which causes potassium efflux and hence hyperpolarisation meaning that a greater depolarisation is required to then reach threshold for firing of an action potential.
Explain the downstream signalling pathway for TrkA.
Nerve growth factor acts on its receptor TrkA after being released from the nerve terminals themselves. Acting on TrkA has a long lasting effect on nociceptor sensitivity and affects the gene expression of ion channels. And also causes an increase activity of ion channels by phosphorylation.
Describe where the ascending pathway and descending pathway travel and their purpose.
Ascending pathway is a neural pathway responsible for the transmission of somatosensory information including pain from the periphery to the cerebral cortex. The descending inhibitory pathway runs from the brain through to the spinal cord to modulate the amount of information received from the periphery to the brain.
Where do the neurons synapse in the ascending pathway?
The peripheral nerve has a peripheral terminal within the target tissue, an extended axon that a cell body within the dorsal root ganglia. A second terminal known as the central terminal is found in the spinal cord.
