Page 381 Slide 3: What is this slide showing?
This slide shows the effects of increasing intensities of a stimulus (bottom record) on
receptor potential (second line) and action potential generation (top two). The locations
of the recordings on the diagram of a nerve fiber are shown on the left. The main points
are: 1) Subthreshold stimuli may be able to generate a receptor potential but if this
depolarization is too small to activate the voltage sensitive sodium channels then no
actions potentials are generated and the information will not reach the CNS. 2) increasing
intensities result in increasing frequency of firing. 3) it is only the action potentials that
are propagated to the CNS.
Page 383 Slide 1: Is the A-alpha fiber not considered a cutaneous nerve
because you just list 3 cutaneous nerve groups?
A-alpha fibers are found in muscle nerves or mixed nerves but not cutaneous nerves
because they arise from muscle spindles. Some books combine the two groups and talk
about A –alpha/beta sensory fibers
Page 389 Slide 1: What is this slide showing?
This slide shows an example of a SAI and an FA1 receptor showing on the left the
receptive field of the afferent and on the right the location of where the subject feels a
sensation when that same afferent is electrically stimulated in the forearm (termed a
perceptive or projected field)
Page 396 Slide 3: What is this slide showing?
This slide shows two additional sensory pathways – the spinocervical tract which
connects the dorsal horn with the lateral cervical nucleus. The lateral cervical nucleus
sends axons to thalamus that ascend in the medial lemniscus. The other pathway relays
muscle afferent information from the lower half of the body to the thalamus via a relay in
Clarke’s column in the thoracic spinal cord and then again in nucleus z in the medulla
and from there via the medial lemniscus to VPL.
Page 400 Slide 3: What is this slide showing?
The two long horizontal bars are raw recordings of neural activity in the thalamus. They
are photographs of an oscilloscope trace. The y axis is voltage and x axis time and the
time scale is given by the bar with '1 sec' underneath. The inset in the top left shows
superimposed action potentials taken from the raw recording and expanded in time so
that the shape of the potential can be seen - you can ignore this. The figurine shows the
location of the receptive of the neuron in each recording. In each recording the vertical
bars are the extracellularly recorded action potentials arising from a single neuron in
VPL. The top trace shows ‘on’ and ‘off’ responses to a tactile stimulus delivered to the
receptive field. The bottom trace shows the slowly adapting responses of a neuron to
application of a tactile stimulus delivered to the tip of digit 5.
Page 403: What do we need to know from all 3 slides?
The projection axons of thalamocortical and coticothalamic neurons send axon collaterals
to excite neurons in the reticular nucleus of the thalamus, which is a thin shell of
inhibitory neurons surrounding most of the thalamus. These projection neurons release
glutamate and are excitatory. They would excite the neurons in the reticular nucleus of
the thalamus. However the reticular neurons release GABA and so when they are excited
they inhibit the cells they project to, in this case the projection neurons in thalamus - so
this is a negative feedback circuit. Knowledge of relative numbers is still sketchy but it is
clear that both are substantial.
Page 406 Slide 2: What is the difference between motion sensitive and direction
sensitive neurons?
Motion sensitive neurons only respond to a stimulus that is moving across the skin rather
than a stimulus that just indents the skin at one point. Direction sensitive neurons are
motion sensitive neurons that also have a selectivity for the direction of the motion across
the skin
Page 417: What is the difference between primary hyperalgesia and flare and
between secondary hyperalgesia and mechanical hyperalgesia?
Mechanical hyperalgesia simply refers to hyperalgesia to mechanical stimulus – i.e.
increased pain to pinching or pressing the skin (in contrast to thermal hyperalgesia).
Primary hyperalgesia refers to hyperalgesia in a region of skin that is damaged and/or
where there is a flare. Secondary hyperalgesia refers to hyperalgesia from a region of skin
that was not damaged and where there is no physical sign of change (e.g. flare).
Page 418 Slide 2: How do you know if its Central or Peripheral?
There is no easy definitive way, however, if one can demonstrate that the neuronal
responses of the sensory afferents are increased (i.e. that the terminals are sensitized) then
this at least provides evidence that some of the hyperalgesia is due to peripheral changes.
This is what this figure shows. If one can find that the responses of the sensory afferents
are unchanged (e.g. from a region of secondary hyperalgesia – not shown) then this
would strongly imply that the hyperalgesia is due central (most likely spinal cord dorsal
horn) changes.
Page 425 Slide 1: What is this slide showing?
These are firing rate histograms (y axis firing rate, x axis time) showing increasing
responses to graded mechanical stimuli in A, response to noxious thermal stimulation in
B and response to application of capsaicin in C. You can ignore part D and E which I
also did not show in class.
Page 428 Slide 3: What is this slide showing?
I deleted this slide from my presentation in class and you can ignore it.
Page 430 Slide 1: What is this slide showing?
This slide shows what is believed to happen in vascular headaches such as migraine. On
the left is a blood vessel (shown in cross section) and a nociceptive primary afferent
encircling it. This afferent has its cell body in the trigeminal ganglion and synapses on
cells in the medullary dorsal horn (the caudal end of the trigeminal nucleus also known as
nucleus caudalis), which project to thalamus. What is hypothesized to happen is that a
trigger stimulus (still not known but probably a chemical released by abnormal activity in
the cortex such as spreading depression) initially excites and perhaps also sensitizes the
nociceptor terminals associated with the major blood vessels and veins and venous
sinuses. This causes the sensory terminals to release SP and CGRP which causes
dilatation and plasma extravasation as well as release of histamine and serotonin from
mast cells and platelets. This causes increased pain associated with a neurogenic
inflammatory response (e.g. increased bradykinin) and from stretching the
mechanosensitive nociceptors in the wall of the vessel. Also shown are 5HT receptor
sites on the terminals of the nociceptors. These are of the 1D subtype and block release of
SP and CGRP. One of the main actions of the antimigraine drugs known as triptans is to
act on these receptors to block release of these peptides.
Page 435 Slide 1: What is this slide showing?
Top diagram shows in a very simplified manner the normal relay of nociceptive
information from periphery to spinal cord dorsal horn spinothalamic tract neurons. This
pathway is only active when there is a noxious stimulus applied to the terminal of the
axon.
The second diagram shows an example of what can happen when the sensory inputs to
the dorsal horn are severed as for example in brachial plexus avulsion. The dorsal horn
neurons lose their normal afferent inputs and can become hyperactive including
spontaneously active as shown in the diagram. Thus in this case pain would be perceived
even though there is no noxious stimulus in the periphery.
The third diagram shows some possible sources of hyperactivity/spontaneous activity
arising from the sensory afferent in a case of peripheral nerve damage. The cut end can
sprout as shown and these abnormal sprouting terminals can become spontaneously
active and/or sensitive to innocuous stimuli. The axon can also become sensitive to
stimuli along its course or even generate action potentials along its course.
Finally, some of your slides refer to Kandel THIRD edition. This edition is
no longer for sale. Do you happen to know where to find the comparable
figures in the 4th edition?
P379 slide 3: 22-5
P380, slide 3: no equivalent
P381, slide 3: no equivalent
P390, slide 3: no equivalent
P392, slide 1: no equivalent
P392, slide 2: 22-13
P395, slide 1: no equivalent
P399, slide 1: no equivalent
P399, slide 2: 21-11
P399, slide 3: 21-11
P405, slide 3: 23-7
P406, slide 1: 23-7
P406, slide 2: equivalent to 23-13, 23-14
P406, slide 3: equivalent to 23-3
P424, slide 1: 24-2
P428, slide 2: 24-3
P432, slide 3: 24-13
P433, slide 1: 24-13