Neurophysiology Flashcards
1
Q
Name the 4 main types of glia.
A
Oligodendrocytes
Astrocytes
Microglia
Ependymal cells
2
Q
What are the differences between glia and neurones?
A
- Newly generated in adult brain (most neurones do not do this, but neurones are regenerated in the hippocampus)
- Do not have an excitable membrane so no action potentials
- Do not form synapses. Doesn’t mean they cannot release neurotransmitters.
3
Q
What is the role of oligodendrocytes?
A
Oligodendrocytes provide insulation to myelinated axons and have a similar role to Schwann cells in the PNS. Oligodendrocytes in the CNS typically myelinate 3-50 axons.
4
Q
What is the role of microglia?
A
Microglia are the principal components of the immune system of the CNS and have a similar role to macrophages.
5
Q
What is the role of ependymal cells?
A
Ependymal cells make CSF in the choroid plexus and keep it circulating through ventricular system with cilia beating.
6
Q
What are the roles of astrocytes?
A
- Extend processes to “fence in” neurones and oligodendrocytes, dendrites, synapses and nodes of Ranvier.
- Help maintain integrity of the blood brain barrier.
- Role in CNS homeostasis, such as spatial buffering of K+.
- “Listen and talk to synapses”.
- Take up and processing of neurotransmitters that spill over from synapses.
- Role in regulating energy supply to neurons and even release gliotransmitters such as ATP and adenosine Radial glia migration of neurones and axonal pathfinding during development.
7
Q
How are neurones highly specialised?
A
- Dendrites are generally specialised for input.
- Information input at synapses on dendrites – convergence.
- Axons are generally specialised for output.
- Information output at presynaptic terminals (branches axons – divergence)
- Neurones integrate and distribute information.
8
Q
Describe the relationship between diameter and myelination.
A
Increasing fibre diameter increases the amount of myelination and increases speed of action potential propagation.
9
Q
Describe the properties of electrical synapses.
A
- Fast transmission
- Bi-directional
- Synchronisation of neural networks
- Synchronisation of astrocyte networks
10
Q
What are the properties of chemical synapses?
A
- Slower transmission
- Essentially uni-directional
- Amplification
- Flexibility
- Plasticity
11
Q
Explain how ionotropic receptors are multimeric.
A
Different subunit compositions give different responses of ionotropic channels to drugs.
12
Q
What is temporal summation?
A
If repetitive stimulation of the same input occur is sufficiently high frequency, their epsps will summate to produce a larger depolarisation, which may reach threshold.
13
Q
What is spatial summation?
A
Sub-threshold epsps and ipsps from synapses at different inputs propagate passively to the axon hillock where they summate. Inputs from distal regions of the dendritic tree will have weaker effects than inputs on the cell soma.
14
Q
Describe presynaptic inhibition.
A
- Release of neurotransmitter can be inhibited by autoreceptor mediated inhibitory feedback.
- Presynaptic/axo-axonic inhibition reduces transmitter release from a presynaptic terminal and can selectively inhibit certain inputs to a neuron without affecting the synaptic integration of other inputs.
- Pre-synaptic receptors can regulate synaptic transmitter release.
15
Q
What are neural circuits?
A
The anatomical specificity of connections between neurones determines how sensory information is processed to produce an appropriate motor response.
Neurones are connected into circuits to process information and produce appropriate responses.
16
Q
What is long term potentiation?
A
High frequency (100Hz for 1 second) presynaptic stimulation of certain glutamatergic synapses results in long-lasting enhancement of transmission, as seen in the greater magnitude and slope of the epsp. Change needed for memory and learning.
17
Q
Describe the action of NMDA receptors being both ligand and voltage gated.
A
- At normal resting potentials Mg2+ ions bind in the open channel, blocking ion flow.
- When the membrane is partially depolarized the Mg2+ is repelled.
- The channel is now permeable to Na+, K+ and Ca2+.
- Increased postsynaptic Ca2+ triggers a series of changes resulting in LTP.
- Ca2+-influx via the NMDA receptor is also thought to be important in excitotoxic neuronal death during stroke. If Ca2+ concentration is too high, causes lytic cell death.
18
Q
What is the link of NMDA to stroke?
A
NMDA receptors can detect coincident pre and posy synaptic activity. The overactivity of NMDA receptors can lead to neuronal death in stroke.
19
Q
What is the purpose of synaptic plasticity?
A
Synaptic plasticity enables experience to change behavioural responses.
20
Q
What is the pavlovian conditioning of the eyeblink reflex?
A
Puff of air to eye > neurone in somatosensory system > synapse to motor neurone > blink reflex
21
Q
What is selective attention?
A
Not all sensory information can be acted upon at the same time. Therefore, the spotlight of attention is moved around, allowing detailed processing of only limited amount of sensory information at any one time. Shifts in attention are driven by internal motivation or external stimuli.
22
Q
What is habituation?
A
One of the ways the brain can cope with sensory information. The responses to constant or predictable sensory stimuli decrease. Occurs to maintained and unimportant stimuli.
23
Q
What is arousal?
A
The state of wakefulness, vigilance and responsiveness to novel stimuli. The level of arousal, attention and behavioural responsiveness is controlled by central neuromodulatory systems.
Unexpected or novel stimuli grab the attentional mechanisms and increase the level of arousal.
24
Q
What are the noradrenergic projections of the ARAS system?
A
Originate in only about 10,000 neurones in the human in a structure called the locus coeruleus, located in the pons, and in related brain stem noradrenergic nuclei. They project to every major region of the CNS. The release of noradrenalin from these projections has an arousing effect on the brain, promoting wakefulness, vigilance and responsiveness to novel stimuli.
25
What are the descending noradrenergic projections of the ARAS?
Form the brain stem to spinal cord via the reticular spinal tract, regulate overall motor tone and pain transmission.
26
What are the serotonergic projections of the ARAS?
Serotonergic projections from the brainstem raphe nuclei are similarly extensive and their projections to the brain modulate sleep, wakefulness and control of mood and behaviour. Projections into the spinal cord affect muscle stone and motor systems and pain perception.
27
What are the dopaminergic projections of the ARAS?
Dopaminergic nuclei projections, such as the ventral tegmental area, is particularly involved in motivation.
28
Define consciousness.
A property of an animal being aware of itself and its place in the environment. clinicians rely on tests of ability to respond to external stimuli.
29
What is fractional loss of consciousness?
Animals with localised CNS damage may not be conscious of certain types of stimuli or places in the environment. such as in neglect, they ignore stimuli on 1 side of the body.
30
What is generalised impairment of consciousness?
Diffuse dysfunction in both cerebral hemispheres, perhaps due to brain swelling, metabolic dysfunction or localised damage to the brainstem arousal system (which is investigated by brainstem reflexes, such as pupillary).
31
What are cholinergic projections from the forebrain?
Cholinergic neurones project from the basal nuclei to multiple brain regions, including the cerebral cortex and thalamus. Use cortical arousal in both awake and dreaming states, as well as modulating attention to sensory stimuli.
32
What are the histaminergic projections from the forebrain?
Histaminergic neurones has innervation from the tuberomammillary nucleus of the hypothalamus, involved in the maintenance of wakefulness.
33
How many hours of sleep per day do different animals?
Python = 18 hours
Tiger = 15.8 hours
Cat = 12.1 hours
Chimpanzee = 9.7 hours
Sheep = 3.8 hours
African elephant = 3.3 hours
Giraffe = 1.9 hours
34
Why do animals sleep?
For rest and recuperation for the section of the day they are not optimally adapted to, reducing predation risk and maintaining energy reserves. However it evolved, sleep is now obligatory and indispensable.
35
How do aquatic animals and birds sleep?
Citations such as whales and dolphins have to periodically surface to breathe so must alternate the side of the brain to sleep, so there is always one active hemisphere.
Some birds that are airborne for long periods has a similar alternating unilateral sleep.
Indus river dolphins that live in low visibility water has to maintain swimming and so microsleeps for only 46 seconds at a time, which adds up to about 7 hours in a day.
36
How can sleep be recorded?
An electroencephalogram, EEG. Performed by veterinary neurologists, particularly in the diagnosis of epilepsy.
Depolarisation of a cell leads to a current slow, which can be recorded on distally placed electrodes, much like an ECG. Difference between EEG and ECG is the size of potentials recorded.
37
Describe the EEG of the awake brain.
High frequency, low amplitude and regular waveform. This is because there are many active brain cells doing tehri own thing at different times.
Wakefulness is characterised by larger and lower frequency waves known as alpha activity, which is an indication of relaxed, awake state.
38
How does the EEG change as the brain transitions to sleep?
- As the brain transitions to sleep, it enters sleep stage 1, characterised by larger and lower frequencies beta waves.
- Stage 2 sleep, characterised by large amplitude K complexes and high frequency sleep spindles.
- Stages 1 and 2 are characterised as light sleep. Transition to stages 3 and 4 marks the transition to deep sleep.
39
What is indicative of delta and slow waves in EEGs?
- Progressively larger amplitude delta waves in the EEG. This are generated by the large scale synchronised depolarisation and hyperpolarisation of cortical cells.
- Stages 1 to 4 are slow wave sleep, thought to be recuperative and restorative in function.
40
Describe REM sleep.
- Brain then returns to lighter sleep and then REM sleep, rapid eye movement sleep.
- This has fast, synchronised, low amplitude EEG activity that is more similar to the waking state.
- In many ways it does seem to be generated by a highly active brain that is processing information.
- But instead of processing sensory information, the brain is replaying experiences in the awake state.
- REM sleep associated with dreaming sleep and memory consolidation.
- Rapid eye movement and respiratory movements are the only body movements that occur.
- There is a general flaccid paralysis of all skeletal muscles, mediated by cholinergic activation of descending inhibitory influences on spinal motor circuits.
- This is to prevents the animal from acting out in their dreams.
41
Describe the neuromodularity activity in the awake state.
Noradrenergic = high
Serotonergic = high
Histaminergic = high
Cholinergic = high
42
Describe the neuromodulatory activity in non-REM sleep.
Noradrenergic = low
Serotonergic = low
Histaminergic = low
Cholinergic = low
43
Describe the neuromodulatory activity in REM sleep.
Noradrenergic = lowest
Serotonergic = lowest
Histaminergic = low
Cholinergic = high
44
What is cataplexy?
A state in which the animal is fully conscious and aware of its surroundings but has flaccid paralysis and is unable to stand or move. Can occur when the cholinergic activation of the descending inhibitory control of the spinal motor circuits is inappropriately activated during wakefulness. this can occur in states of excitement, such as dogs playing. As they become excited, their movements become weaker and less coordinated until collapse.
45
What are circadian rhythms?
All nucleated cells in the body have an intrinsic daily rhythmicity. For controlling body temperature, hormonal levels, including glucocorticoids and growth hormone, as well as the sleep-wake cycle.
46
How are circadian rhythms generated?
- Superchiasmatic nucleus in the hypothalamus acts like a pacemaker.
- Has clock control genes that produce a protein that inhibit their own expression.
- Levels increase and decrease in a daily cycle, which seem to affect membrane potential, and so neurones in the SCN have neurone fire rates twice as high in the day than at night.
- The molecular clock in the SCN is kept in synchrony with environmental changes, largest determinator being light levels.
47
What is the awake state driven by?
Activity of neurones in the lateral hypothalamus, which contain the peptide neurotransmitter, hypocretin.
48
Describe the action of hypocretin.
- Secrete hypocretin to excite neurones in the brainstem and forebrain arousal systems, which maintain the alert waking state by cholinergic, noradrenergic, histaminergic and serotonergic release.
- These arousal systems also inhibit a sleep promoting region in the ventral lateral preoptic area of the hypothalamus.
- This reciprocally inhibits the arousal system via GABAergic transmission in a mutually inhibitory flip-flop arrangement.
- So wakefulness inhibits sleep and sleep inhibits wakefulness, which helps to maintain the stability of each state.
49
How is there a switch between wakefulness and sleep?
- Hypocretin check neurones in lateral hypothalamus are excited by the motivation to stay away from other forebrain areas and excitatory input from the superchiasmatic nucleus of the hypothalamus.
- This conveys the daily biological rhythm that synchronises the sleep-wake cycle with the external environment.
- Sleep is controlled by the circadian clock in the hypothalamus. This does not cause sleep, merely its timing.
- The longer the animal stays awake, the higher the levels of adenosine that accumulate in the brain, as a product of metabolic activity.
- Adenosine excites the VLPA and its activity increases to a level where it inhibits the arousal system and leads to sleep.
50
What is narcolepsy?
An irresistible urge to sleep, which progresses rapidly into REM sleep without prior slow wave sleep. Attack can be brief with full consciousness regained quickly. Not common in dogs but does occur. Normally due to recessive inherited defects in the hypocretin system of the lateral hypothalamus, such as a receptor dysfunction. Attacks may be triggered by arousing situations, such as in cataplexy. Flaccid paralysis associated with REM sleep state occurs.
51
Describe anaesthetic drugs that increase GABAergic inhibitory transmission.
Including pentobarbitone and profanol. Can act at the inhibitory synapses from the VLPA sleep promoting region to turn off arousal systems and effectively send the animal to sleep.
52
Describe anaesthetic drugs that antagonise NMDA receptors.
Ketamine. This decreases excitatory transmission. In certain species, they can be combined with alpha-2 adrenergic agonists. Noradrenergic nerve terminals have presynaptic alpha-2 receptors that normally mediate autoinhibition to limit noradrenaline release. Treatment with an alpha-2 agonist can therefore inhibit the release of noradrenaline and have sedative effects by decreasing arousal.
53
Describe gaseous anaesthetics.
Such as halothane and isofluorane. Thought that they act on 2 pore potassium channels to hyperpolarise neurones.
54
What are interoceptors and their roles?
Sensory systems that collect information about the internal body state.
- Homeostatic regulation – temperature, stretch receptors and fluid balance
- Control of autonomic body functions – gut motility
- Motor control – balance, locomotion, movements, vocalisation
55
What are exteroceptors and what are their roles?
Sensory systems that collect information about the external environment.
- Recognise external threats – predators and stressors
- Recognition of external resources – food and mates
- Synchronisation of body and environment – seasonal breeding
56
How are mechanoreceptors involved in mechanical stimuli of sensory pathways?
- Hearing and balance – hair cells, lateral line organ
- Touch – skin mechanoreceptors (ion channels that are sensitive to chemical stimuli, tension changing the conformation of the ion channel) vibrissal receptors
- Proprioception – joint receptors, muscles spindles, Golgi tendon organs
57
Which somatic senses are information from the skin and musculoskeletal system?
- Touch – cutaneous tactile sensation, vibrissae
- Nociception – pain, itch, irritation
- Temperature
- Proprioception – joint receptors, muscle spindles, Golgi tendon organs
58
What is somatosensory information?
Limbs and trunk via dorsal root ganglion. Cranial structures via cranial ganglia.
Somatosensory system collects information about touch, pain, itch, temperature and proprioception via different types of sensory receptor neurones.
59
Describe the chemical receptors in sensory systems.
- Chemicals – visceral chemoreceptors, taste, olfactory receptors, nociceptors, itch receptors
- Light – photoreceptors
- Temperature – thermoreceptors
- Electrical – ampullary receptors, tuberous receptors (important for aquatics like sharks and rays)
- Magnetic? – some birds may be able to sense for navigation
60
How is a sensory stimulus modified and filtered?
1. Stimulus
2. Modification: tissue outside sensory cell
3. Modified stimulus
4. Transduction and amplification in receptor membrane of sensory cell
5. Graded receptor potential
6. Coding in membrane of sensory nerve fibre
7. Nerve impulses to the CNS
61
What is adaptation of sensory cells?
Adaptation – reduction in the response of a receptor over time in the presence of a constant level of stimulation.
Adaptation makes receptors more sensitive to changes in intensity than absolute level. This reduction in sensitivity can shift the working range of receptors to cope with a wide range of a stimulus intensity.
62
Describe Pacinian corpuscles as an example of adaptation.
Initial pressure in a Pacinian corpuscle, fluid is incompressible, and transmitted pressure to nerve ending. Polarisation and action potential of nerve ending, after this, fluid in lamellae has chance to flow away to relieve pressure on the nerve ending. This relieving of fluid means there is not constant stimulation of the nerve ending. Accessory structure is filtering the stimuli coming in to make receptor sensitive to changes in the stimulus coming in and not the constant stimulus.
63
What are Meissner's corpuscles and Merkel's discs?
Located superficially in the glabrous skin, neat the border of dermis and epidermis. They are sensitive to slight indentations of the skin surface.
64
What are Pacinian corpuscles and Ruffini endings?
Pacinian corpuscles and Ruffini endings are located more deeply in the dermis and will be stimulated by larger scale mechanical deformation of the skin.
65
Describe the types of receptors in glabrous and hairy skin.
There are differences in the receptor types found in hairy skin and glabrous skin (palms, fingertips, lips of primates, footpads and nasal rhinaria of other species).
Hair follicles are innervated by hair sensory afferents, which provide information about hair movement and have a similar functional role as the Meissner’s corpuscles in glabrous skin.
66
What is the receptive field of a neurones?
Area of sensory space in which a stimulus elicits a change in its activity. The receptive field of a tactile afferent will be within a dermatome, a region of skin innervated by a nerve from a specific spinal level.
67
What is the variety in receptive fields?
Superficial receptors have small receptive fields ad sense fine details and textures.
Deep receptors have larger receptive field sizes
Ruffini endings are sensitive to the direction of skin stretch
68
How is different touch information provided by different superficial and deep receptors?
Deep are single afferent fibres and go to a wide area of skin/larger receptive field. Superficial ave narrower receptive fields. Slowly adapting or Merkel’s superficial and Ruffini deep. Rapidly adapting is Meissner’s superficial and Pacinian deep.
69
What is spatial acuity?
Spatial acuity varies across body surface in relation to peripheral innervation.
For most animals, the face and lips have the highest density of receptors and the highest spatial acuity and are the most sensitive to touch.
70
What is the dorsal column pathway?
Dorsal column medial lemniscal system conveys information about touch and proprioception in kinasthesia.
Somatosensory cortex receives information about touch from the contralateral side of the body
71
Describe the process of the dorsal column pathway.
1. Tactile and proprioceptive somatosensory afferents project axon collaterals to local spinal circuits, where they can mediate spinal reflexes to control the motor system.
2. Sensory afferents also ascend the spinal cord ipsilaterally to the dorsal column nuclei in the medulla, the gracile and cuneate nuclei, then decussate to the contralateral side of the brainstem and ascend in the medial lemniscus to synapse on neurones in the ventral posterior lateral nuclear of the thalamus.
3. These 3rd order neurones then synapse in the primary somatosensory cortex on the contralateral side of the body.
72
What is a somatotopic map?
Neighbouring areas of somatosensory cortes respond to input from neighbouring area of skin, forming a somatotopic map of body surface.
Regions of the body where touch information is more important have higher number of sensory receptors and a greater area of cortex to process the information.
73
What is cortical magnification?
A greater amount of cortex is devoted to processing information from more important regions. This is partly due to greater peripheral receptor density but partly due to extra cortical magnification.
74
List the names of the species cortical magnifications.
- Sensory homunculus in humans
- Sensory felunculus in cats
- Sensory cannunculus in dogs
- Sensory equnculus in horses
- Sensory bovunculus in cows
75
What are vibrissae and their function?
An enormous number of hair cell afferents make them directionally sensitive to displacements of 0.001mm.
Form of exploratory behaviour linked to sniffing behaviour in order to gain information from an environmental stimulus.
76
What are the species variations in vibrissae?
- Particularly important to nocturnal and burrow living species, enabling navigating and exploration in complete darkness.
- Longer and more highly innervated in aquatic species.
- Herbivore vibrissae for blind spot.
- Seals use vibrissae to detect vibrations in water from their prey.
77
What is experience dependent plasticity?
- Maps are not fixed but change with sensory experience or peripheral damage.
- Such plasticity also allows a degree of functional recovery following intracerebrovascular accidents, such as stroke.
- Brain function is continually being remodelled by experience and can recover function following stroke.
78
Describe the different somatosensory fibres.
Afferents conveying touch information are predominantly A beta fibres that have fast conduction velocities of around 35-73m/s.
Small unmyelinated C type fibres innervate down hairs with very slow conduction velocities. This implies that they have a different functional role. They respond to light stroking and potentially mediate what is known as affective touch.
79
What is affective touch?
- Mediated by C-fibre tactile afferents
- Optimal stimulus is slow stroking of skin – 3cm/sec
- Input to brain areas involved in perception of body state and pleasure, such as insular cortex and anterior cingulate cortex.
- Human patients who have lost normal tactile perception mediated by somatosensory cortex are still able to report pleasurable sensation from stroking
80
Describe the distribution of thermal sensory afferents.
Thermal sensory afferents are distributed more sparsely than touch afferents, leading to a spotty distribution of sensitivity on the skin.
Function of cutaneous thermal sensation is to provide information about environmental temperature, which does not need to be sampled evenly over the entire skin surface.
81
What are thermal sensory afferents?
Free nerve endings without any accessory structures. Their sensitivity is conferred by the presence of ion channels of the transient reception potential family.
82
How do different temperature receptor channels have different thermal ranges?
Cool fibres increase their action potential firing rate over a range of cool temperatures.
Warm fibres respond to an overlapping and higher temperature range.
83
What is temperature adaptation?
When stimulated with a drop in temperature, cold responding fibres will increase their firing rate and warm responding fibres will decrease their firing rate. But these responses adapt rapidly and decrease to close to the original firing rate. This adaptation means that these receptors are signalling changes in temperature more reliably than absolute temperature.
84
What are grimace scales?
The assessment of pain has to be made in the context of deviation from normal appearance and behaviour typical for the species and even the individual animal. This has recently led to the production of grimace scales for laboratory animal species , such as mice and rats. These are used t score different aspects of facial appearance that are related to signs of pain to provide an overall pain score as a measure of the animal’s experience of pain.
85
Describe acute pain.
- Immediate and transient pain response to a damaging or potentially damaging stimulus. It is often associated with reflex withdrawal, vocalisation or biting.
- This is what you would call physiological pain, which performs a vital function for the animal.
- If an animal were to lack pain perception, it would not survive vert long, as it would not avoid damaging situations.
86
Describe chronic pain.
- A persistent aching pain which may be associated with species-specific behaviours, such as rolling, facial grimacing, hunching and listlessness and withdrawal from normal behavioural responses.
- Can arise from different sources.
- Inflammatory pain, in which chemicals released during inflammatory processes stimulate and sensitise pain afferents.
- This is also physiological pain in that it helps to protect the inflamed area from further damage.
87
What is neuropathic pain?
- Another form of neuropathic pain.
- This is caused by a dysfunction in the nervous system.
- This is a pathological pain, which is difficult to treat an excruciating pain that occurs in the absence of any tissue damage or inflammation.
88
What produced the sensation of pain?
Damaging or potentially damaging stimuli that produce the sensation of pain are sensed by nociceptors. This includes strong mechanical stimuli and trauma, damaging heat or cold and chemical stimuli that are released from damaged cells, including ATP, H+, K+ and bradykinin.
89
Describe nociceptive afferents.
- Like temperature sensation, pain is sensed by free, unencapsulated nerve endings in the skin, known as nociceptors, which penetrate the keratinocyte layer of the epidermis.
- It has been thought that nociceptors act independently of any associated cells but recent studies suggest that the keratinocytes in the epidermis are also able to signal to nociceptive afferents and may play a role in sensing nociceptive stimuli.
90
How do nociceptive stimuli generate action potentials?
- Activation of receptors or ion channels on nociceptors lead to depolarisation of the nerve ending and the generation of action potential via voltage activated sodium channels.
- As well as conventional types of voltage gated sodium ion channels, there are specific types of sodium ion channels called NaV1.7 found exclusively in nociceptors.
- Mutations that increase the function of NaV1.7 are associated with pain syndromes and loss of function of NaV1.7 is associated with congenital insensitivity to pain.
91
Describe how different nociceptors have different sensitivities.
Adapted to the type of damaging stimulus to which they are exposed and the potential for tissue damage to occur.
- For example, the cornea is extremely sensitive to stimuli such as hair and dust that would not evoke pain on contact with the skin.
- Cutting and piercing damage to the skin is much more painful than the same type of cutting stimulus in the viscera.
- But visceral nociceptors are more sensitive to stretch and distension, which is more likely to occur in and potentially damage the viscera.
92
What is sensitisation of nociceptors?
Pain differs from other sensations in that the pain response is normally increased to prolonged or repeated stimulation.
Sensitisation of nociceptor afferents increases their sensitivity and the pain response that is evoked (analgesia).
93
Use bradykinin as an example to explain sensitisation of nociceptors.
- Bradykinin, a pain inducing chemical stimulus, initially produces only a very low firing rate in a pain afferent.
- Treatment with sensitising factor prostaglandin E2 doesn’t not stimulate action potential firing itself.
- But subsequent treatment with the original dose of bradykinin now evokes a high rate of afferent firing.
94
Describe sensitisation by prostaglandins.
- The mechanism for sensitisation by a variety of molecules (PGE2, adenosine, serotonin) is via increases in intracellular cAMP.
- This has a direct effect on increasing sodium ion influx, which depolarises the resting membrane potential, along with phosphorylation of a voltage gated sodium ion channel.
- This increases its probability of and therefore decreases threshold for action potential generation.
95
How are epithelial cells a source of sensitising factors?
Such as keratinocytes in the epidermis. Damage to these cells releases pain evoking stimuli, such as ATP and H+, which are also sensitising factors along with prostaglandins.
96
How are blood vessels a source of sensitising factors?
By endothelial cells of blood vessels, a potent vasodilator but also sensitising factor for nociceptive nerve endings.
97
How are sympathetic postganglionic neurones a source of sensitising factors?
Release sensitising factoring including ATP and noradrenaline.
98
How is the immune system a source for sensitising factors?
A rich source of inflammatory mediators, that are also sensitising factors for nociception – histamine and cytokines, such as interleukins, which stimulate prostaglandin synthesis, a pathway targeted by NSAIDs to have analgesic effects.
99
Define hyperalgesia.
Increased pain response to a normally painful stimulus.
100
How do the nociceptive afferent fibres themselves cause sensitising stimuli?
- Action potentials are also transmitted backwards along axon collaterals to invade other nociceptive terminals of the same afferent in the surrounding area of skin.
- These release substance P and CGRP, which are peptides that act as inflammatory mediators.
- These peptides cause vasodilation of local blood vessels, which result in the flare response.
- This increase in pain sensitivity due to inflammation and sensitisation is known as primary hyperalgesia.
101
What is a consequence of the of nociceptive afferents providing sensitising stimuli?
A consequence of this axon reflex is that an abnormal overactivity of nociceptors can lead to neurogenic inflammation – pain and inflammation generated by the dysfunction in the pain afferent fibres in the absence of actual tissue damage.
102
How is skin cooling detected?
Cool receptors, A-delta fibres
103
How is skin warming detected?
Warm receptors, C fibres
104
How is hot temperature detected?
Heat nociceptors, A-delta fibres
105
How is cold temperature detected?
Cold nociceptor, C fibres
106
How is sharp prickling pain detected?
Mechanical nociceptors, A-delta fibres
107
How is burning pain/freezing pain?
Thermal/mechanical nociceptor, A-delta fibres
108
How is slow burning pain detected?
Polymodal nociceptor, C fibres
109
Describe fast pain.
A delta fibres are small myelinated fibres that mediate the fast components of pain. This initial fast pain is perceived as a well localised, sharp, pricking pain. This elicits withdrawal reflexes and attention to painful stimuli.
110
Describe slow pain.
The slow components of pain is conveyed by small unmyelinated C fibres. This slow components is perceived as a prolonged, poorly localised, aching and emotive pain. this changes behaviour of the animal to protect damaged tissue and provides the motivation to avoid the same damaging situation in the future.
111
How can slow and fast pain types be dissociated experimentally?
- Application of pressure to a nerve will block transmission in larger diameter A delta fibres before the small unmyelinated C fibres. Blocks sharp pricking pain leaving the unpleasant emotive component of pain intact.
- Local anaesthetics block transmission in the small unmyelinated C fibres before they block larger A delta fibres. This leaves the sharp pricking fast pain intact but blocks the unpleasant emotive slow pain.
112
What is flexion withdrawal reflex?
Main role of A delta pain pathway. Means the circuit involves transmission across more than 1 synapse from the pain afferent input to indirectly excite alpha motor neurones controlling flexor muscles and indirectly inhibit alpha motor neurones controlling extensor muscles. This result of the reflex withdraws the limb away from painful stimulus to reduce damage.
Used in neurological exams and to test the depth of anaesthesia.
113
How do afferents convey touch information directly to the dorsal column nuclei?
- Pain and temperature afferents synapse on 2nd order pain transmission neurones in the spinal cord.
- They decussate and project up the contralateral side in the ventrolateral spinal tracts/anterolateral system.
- Fast pain information via the thalamus to the primary somatosensory cortex.
- Slow pain information via the thalamus to the insular cortex.
114
What is periaqueductal grey area?
Stimulation of this area in the midbrain is able to induce a profound analgesia, without affecting responses to touch, pressure or temperature. Stimulus also able to inhibit withdrawal reflexes to painful stimuli.
115
Describe stimulation of the PAG.
- Occurs because there are descending pathways from the PAG via serotoninergic neurones in the nucleus raphe-magnus in the medulla and from descending noradrenergic neurones form the locus coeruleus in the pons, which excite interneurons in the dorsal horn of the spinal cord.
- Interneurons release endogenous opioids, such as enkephalin, blocking activity in the transmission cells, blocking the transmission of pain information at the spinal level.
116
What is the advantage and disadvantage of activating the PAG?
This system can be activated in fight or flight type situations where the animal’s survival depends on suppressing the normal responses to pain.
But activation of this system can also lessen pain responses in stressed patients in the clinic, making them more difficult to diagnose.
117
What is present in all vertebrae and some invertebrates? How does this vary between species?
Homologues of the insular cortex and anterior cingulate cortex are present in the brains of all vertebrates and some invertebrates like cephalopods. So we should assume that all these animals have the capability to feel the unpleasant emotional aspect of pain.
Degree to which the prefrontal cortex is involved in recognising long-term emotional implications of pain varies with species, as opposed to the current emotional experience of pain.
118
What are the behavioural contexts of pain?
- Sensory stimulation of larger diameter touch afferents can inhibit pain transmission neurons in the spinal cord. So, rubbing, shaking or licking the affected area can lessen pain perception.
- Individual psychological factors will influence pain perception: anxiety, attention and stress can all enhance pain perception, as will previous painful experiences.
- Behavioural context can also influence pain perception via the descending control pathways. So, pain perception can be reduced when in survival conditions or when feeding, fighting or mating.
- Prey species evolved to mask outward signs of pain to advertise injury to predators.
119
How does itch direct scratching behaviour to the site of irritation?
- Mediated by a distinct neural pathway, also conveyed by slowly conducting C fibres and via the spinothalamic tract but with a different pattern of thalamic and cortical projection to pain and perception.
- Can result from acute exposure for instance an insect bite, allergen, chronically in inflammation conditions, drug reactions, or systemic disorders. So renal failure and liver failure can be associated with widespread itching.
- Some itch fibres are highly sensitive to histamine, which induces itch, but are not sensitive to noxious mechanical or thermal stimuli.
