lecture 19 Flashcards
pain
1
Q
How do we define pain?
A
Nociception: activation of nociceptive primary afferents; cutaneous and internal, the physiological aspect of detecting pain-causing stimuli
Pain: conscious, affective unpleasant somaesthetic percept localised to the body
Hyperalgesia: increased sensitivity to noxious stimuli
2
Q
What is an experimental demonstration that nociception involves specialised neurons?
A
- insert a small electrode/recorder into skin to a pain receptor
- use heat (doesn’t stimulate other nerve fibres i.e. touch mechanoreceptors)
- map receptor field of a single nociceptor fibre
- they have a very high threshold for activation
- they don’t respond until things get quite high energies
- the non-nociceptive thermoreceptor is sensitive early on but plateaus after a certain point (~42ºC) while the nociceptor only begins firing at this temperature and increases firing with increased heat
3
Q
What are the different types of nociceptor afferents?
A
- nociceptors are the thinnest nerve fibres in the periphery
- they are either unmyelinated (C fibre) - myelin would actually slow down the conduction of the impulse in a fibre this small; very slow conduction (less than walking speed)
- A-delta fibres: thinly myelinated, ~5µ, faster, tend to signal different aspects of noxious stimuli, high-threshold mechanoreceptors
- fast, sharp pain sensation (A-delta)
- C fiber - diffuse or duller burning pain
- most C fibers don’t respond to just one stimulus
- noxious mechanical injury, chemical, high acid [H+], various other inflammatory mediators
4
Q
What is the association between axon size, conduction velocity and somatosensory modality?
A
A-alpha
- big (13-20µ), fast (80-120m/sec), highly myelinated
- proprioreceptors of skeletal muscle
A-beta
- myelinated
- 6-12µm
- 35-75 m/sec
- mechanoreceptors of skin
A-delta
- 1-5µm
- 5-30 m/sec
- pain, temperature
C
- 0.2-1.5 µm
- 0.5-2 m/sec
- temperature, pain, itch
- there’s more C fibres than anything else, every tissue in the body has innervation from C fibres
- massive, broad innervation so need small diameter
5
Q
What activates nocireceptors?
A
- heat
- H+ concentration
- chemicals such as capsaicin (found in chiles), lipid soluble molecule that diffuses through the membrane and acts on an internal part of the receptor
- a lot of these act at a single molecular place in these nerve membranes
- VR-1 receptors
- also mechanical gated channels
- these agents lead to depolarisation of the neuron (cation channels)
6
Q
What is the pathway of a nociceptive afferent?
A
- cell body in dorsal root ganglion
- nociceptors invariably do their transmitting locally
- within a segment or two of entering the spinal cord they find their postsynaptic cell
- the postsynaptic cell is usually sitting in the very superficial part of the dorsal horn
- this first synapse is usually the first opportunity for things like drugs to work (not counting periphery)
- second neuron does long range projection up the spinal cord to brainstem and thalamus
- second neuron decussates
- travel in anterior and lateral part of the white matter
- aka Anterior Lateral System (ALS) aka spinothalamic tract
- second neuron has targets in the thalamus (also other places in the brain stem)
7
Q
What happens in the superficial dorsal horn?
A
- nervous system organised in layered system
- C fibres invariably synapse in the superficial dorsal horn (directly or via interneurons to decussating neuron)
- A-delta fibre: synapses on superficial dorsal horn neurons (perhaps converging onto same neuron), also has some projection neurons in layer V (smaller proportion)
- we seem to get convergence of the specificity/differences of the peripheral nociceptors in the spinal cord, even converging on cells that get touch AND nociceptive information
- unclear how we get such a clear distinction between painful and non-painful stimuli etc
8
Q
What different symptoms might you get in a lesion of the spine based on its location?
A
‘Textbook lesion’ - what would happen if half of your spinal cord was cut
- on the opposite side to the lesion you have reduced sensation of temperature and pain
- on the same side as the lesion you have reduced sensation of two-point discrimination,vibration, and proprioception
‘harlequin sensory loss’
- you also have a zone of complete loss because there are a few segments where the nociceptors travel before they decussate
9
Q
Where does the anterolateral system send information?
A
Different parts of the brainstem/forebrain
- (major target) ventral posterior nucleus –> somatosensory cortex (S1, S2) – sensory-discriminative (location)
- midline thalamic nuclei –> anterior cingulate cortex and insular cortex (affective-motivational) (pain is extremely motivational)
generating conscious experience of pain/what it is what it feels like (also the midline thalamic nuclei)
- reticular formation
- superior colliculus
- periaquiductal grey
- hypothalamus
- amygdala (key structure in negative experience/emotions)
10
Q
What is the cingulate cortex?
A
- 1cm - 1.5cm of cortex that sits above the corpus callosum
- right on the midline
- anterior: where a lot of the nocireceptor pathways seem to end/location of cortical targets (3rd neuron in path from thalamus to anterior cingulate)
- a lot of emotional states that we experience seem to require anterior cingulate cortex e.g. hunger, thirst, pain
11
Q
What is the insula cortex?
A
- quite internal (if you cut out part of cortex just superior to sylvian fissure - underneath
- gets a lot of input from nociceptors, also visceral nociceptors (viscerotropic)
- also gets interoceptive input e.g. porcinian corpuscles in the peritoneal cavity
- mysterious
- might have something to do with how we localise that pain as our own
- ‘my’ body
12
Q
What are pathways mediated discriminative aspects of pain/temperature for body and face?
A
- primary afferent containing pain and temperature information from lower body enters lumbar spinal cord
- cervical spinal cord for upper body excluding face
- second neuron (projection neuron in superficial layer of dorsal horn) decussates - anterolateral system
- travels through brainstem to thalamus (spinothalamic tract)
- third order neuron in thalamus that meets cortical targets
- for face: trigemino nucleus - pain and temperature info, spinal trigeminal tract (afferent axons) come down to caudal medullar to find a place to decussate, trigemino-thalamic tract
13
Q
What activates the receptors on C fibres?
A
- think of things that are present when skin is damaged
- H+
- 5-HT
- Bradykinin
- ATP (extracellular)
- prostaglandin
- histamine (released by mast cell or neutrophil)
14
Q
What happens when a C fibre is stimulated?
A
- apart from the action potential that travel to the spinal cord
- we have nerve impulses that after travelling retrogradely, travel anterogradely at branching points where they actually release compounds
- sensory and effector
- release small peptides e.g. substance P (stimulates mast cells or neutrophils) or CGRP (calcitonin gene related peptide) which acts on blood vessels
- these are inflammatory
- vasodilation, histamine release
- very short reflex
15
Q
How can we think of pain as a homeostatic system?
A
- it’s a mechanism of maintaining the integrity of tissue
- mechanism of detecting damage and of reversing damage (C fibres)
- have a homeostatic conscious mechanism - behavioural mechanisms
