1) The document discusses the neuroanatomy and pathways involved in nociception and pain perception. It describes the receptors, fibers, and central processing involved in transmitting information about potentially damaging stimuli. 2) There are two main pain pathways - one transmitting fast, sharp pain via Aδ fibers and another transmitting slow, dull pain via C fibers. Both pathways involve neurons in the dorsal horn and thalamus. 3) Modulation of pain occurs via descending pathways from the brain and interactions between nociceptive and non-nociceptive fibers in the spinal cord. Dysregulation of these systems may contribute to chronic pain states.

1. Domina Petric, MD
Pain systems

2. Nociception is perception of pain (modality of somatic
sensation).
There is affective component of pain which is very important.
Secondary affect phenomenon exmplains how the impact of
chronic pain affects the emotional life.
Psychosocial context is very important in understanding pain:
it has significant impact in modulating the experience of pain.
Nociception

3. Free nerve endings of pheripheral axon is the receptor for
pain.
Cell body of first order neuron is in the dorsal root
ganglion.
Central process of first order axon synapses with the
second order neuron in the dorsal horn of the spinal cord.
Pain

4. o Free nerve endings are receptors for sensation of pain.
o Free nerve endings distribute broadly within the tissues: large
receptive fields.
o Pain fibres are Aδ fibres and C fibres (unmyelinated).
o Aδ fibres include axons that are sensitive to mechanical stimulation
that can lead to nociception.
o There is also a type of Aδ fibre that is sensitive to both mechanical
energy and thermal energy when there is a risk for tissue damage.
o Conduction velocity of C fibres is smaller than the Aδ fibres.
Receptors, fibres

5. C fibres are polymodal: respond
to multiple modalities of energy
or chemical conditions that can
potentially cause damage to
tissue (mechanical, thermal,
chemical stimuli).
Receptors, fibres

6. o Channels in nociceptors belong to the transient receptor
potential family of ion channels.
o TRP channels may be sensitive to heat or cold or protons in
accidic conditions.
o TRP channels have modulatory sites for organic compounds
(capsaicin).
o When TRP channels open, cations like sodium and calcium ions
can influx into the cell.
o If there is potential above the treshold, we call it action potential.
Sensory transduction in nociceptors

7. Substantia gelatinosa (lamina 2 of the dorsal horn):
second order neuron for processing pain.
C fibres terminate superficially in the marginal zone
(lamina 1) and in the substantia gelatinosa (lamina 2).
Aδ fibres terminate more deeply (laminae 5 and 6)
Dorsal horn of the spinal cord

8. o Also called second pain that evolves
more slowly and persist for longer
period of time.
o C fibres give rise to projections (after
the laminae 1 and 2) that go into the
brainstem and some of the fibres go
to the thalamus (synapse in medial
nuclei of the thalamus).
o Emotion and cognition about
nociception (ventral and medial parts
of the forebrain or limbic system)!
Throbbing pain
o Also called first pain that
subsides in a matter of seconds.
o Aδ fibres give rise to projections
that go directly to the thalamus
(ventral posterior complex) after
the laminae 5 and 6.
o Signals go to somatosensory
cortex in postcentral gyrus.
o Localisation of nociception!
Sharp shooting pain
Two categories of pain sensation

9. First pain:
spinothalamic tract Second pain pathway
Aδ
Second
order
neuron:
laminae
5 and 6
Cross
midline
Ventral
posterior lateral
thalamic
nucleus
Somatosensory
cortex (S1, S2)
C
Second
order
neuron:
laminae
1 and 2
Crossing
midline
Midline
thalamic
nuclei
Anterior cingulate
cortex, insular
cortex
Reticular
formation,
superior
colliculus,
periaqueductal
gray,
hypothalamus,
amygdala

10. Reticular formation and periaqueductal gray
matter
Reticular formation:
o multiple small nuclei
o level of arousal and attention
o modulation of cognition and responses to pain
Periaqueductal gray matter:
o top down or the feedback modulation of pain transmission in
the dorsal horn of the spinal cord

11. Insular cortex: processing emotional signals,
building an image of the body that is especially
informed about the internal state.
Anterior cingulate cortex: participates in prefrontal
cortical networks that are involved in evaluating the
significance of the consequence of our actions.
Insular and anterior cingulate cortex

12. o Enchanced sensitivity to mechanosensory stimulation.
o Tissue damage causes tissue inflammation and immune response.
o Immune mediators have impact on the nociceptors (free nerve
endings): bradykinins, ATP, prostaglandins, histamin, hydrogen
ions...
o Immune mediators can increase currents that flow through TRP
channels of the nociceptors: there is an increase of sensitivity of
free nerve endings.
o Allodynia: stimulus is perceived as painfull, although there is no
tissue damage.
Hyperalgesia

13. When there is repeated
activation of
nociceptors, it leads to
sustained depolarisation
of that neuron.
Wind up phenomenon

14. Descending pathways that modulate pain
Somatic sensory cortex
Amygdala Hypothalamus
Periaqueductal gray
Parabrachial
nucleus
Medullary
reticular
formation
Locus
coeruleus
Raphe
nuclei
Dorsal horn of spinal cord
Anterolateral
system

15. Descending pathways that modulate pain
Periaqueductal grey is a key node in a
network that allows for the feedback
modulation of pain.
Locus coeruleus releases norephinephrine
in the dorsal root of the spinal cord and
raphe nuclei release serotonin.

16. Activation of, for example,
mechanoreceptors can,
because of competition
with stimulated
nociceptors, inhibit
nociceptors.
Gate theory of pain (feed forward modulation
of nociception)

17. Nociceptive chronic pain results from ongoing
stimulation of nociceptors.
Involves both first and second pain.
Chronic pain syndrome is chronic pain with no
known nociceptive etiology.
Dysregulation of feedback descending
systems?
Chronic pain

18. o Abnormal activity in nociceptive pathway unrelated to the
presence of a nociceptive stimulus.
Mechanisms:
o nerve compression
o abnormal somatic sensation
o sustained senzitisation of neurons in nociceptive pathway
o abnormal activity in sympathetic outflow to viscera
o maladaptive plasticity in higher centers (phantom sensation)
Neuropathic pain

19. II.
Pain and temperature
pathways

20. Two pairs of
somatosensory pathways
Post-cranial body:
posterior part of the
head and body below
the head
Dorsal column
medial lemniscal
system:
mechanical
stimuli
Anterolateral
system: pain and
temperature
Face and anterior
portion of the head
Pathway through
the principal
sensory
trigeminal
complex nucleus:
mechanical
stimuli
Pathways
through the
spinal trigeminal
complex nucleus:
pain and
temperature

21. Anterolateral system

22. First pain:
spinothalamic tract Second pain pathway
Aδ
Second
order
neuron:
laminae
5 and 6
Cross
the
midline
Ventral
posterior lateral
thalamic
nucleus
Somatosensory
cortex (S1, S2)
C
Second
order
neuron:
laminae
1 and 2
Cross the
midline
Midline
thalamic
nuclei
Anterior cingulate
cortex, insular
cortex
Reticular
formation,
superior
colliculus,
periaqueductal
gray,
hypothalamus,
amygdala

23. Second order neurons cross
the midline in the ventral white
commissure of the spinal cord
and enter the anterolateral
white matter of the spinal cord.
Spinothalamic tract

24. o First order neuron is in the trigeminal ganglion and sends
axons that are descending in the spinal trigeminal tract
(afferent axons).
o Those axons synapse in the spinal nucleus of the
trigeminal complex.
o From the spinal nucleus neuron grows an axon that enters
the lateral tegmentum of the brainstem and ascends.
o Third order neuron is in the ventral posterior medial
thalamic nucleus.
Trigeminothalamic tract: pain and
temperature from face

25. Trigeminothalamic tract: pain and temperature from the face
First order
neuron:
trigeminal
ganglion
Spinal trigeminal tract:
descending afferent
first order axons
Second order neuron:
spinal nucleus of
trigeminal complex
Axons cross the midline
Axons
ascend the
lateral
tegmentum
Third order
neuron: ventral
posterior medial
thalamic nucleus
Somatosensory cortex

26. Loss of pain and temperature
on the one side of the body
and loss of mechanosensation
on the other side of the body
when there is one-sided lesion
of the spinal cord.
Dissociated sensory loss

27. o Visceral pain is derived from Aδ fibres and C fibres that are
innervating the viscera.
o Their axons then join the anterolateral pathway.
o There is an additional pathway that runs in dorsal columns.
o From dorsal columns axons after crossing midline go via the
medial lemniscus to the ventral posterior thalamic nuclear
complex and then to the insular cortex.
o Insular cortex serves as a somatosensory cortex for the
viscera.
Dorsal column visceral pain pathway

28. https://www.coursera.org/lea
rn/medical-neuroscience:
Leonard E. White, PhD, Duke
University
Literature