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DENT/OBHS 131
Neuroscience
PAIN!
!!
2009
Pain….
Is a submodality of somatosensation
Is the perception of unpleasant or aversive
stimulation (sensory and emotional
experience)
Warns of injury (physiological relevance)
Is highly individual and subjective
General topics
 Brief review of somatosensation
 Anatomical pathways
 Substance P
 Nociceptors
 Gating theory
 Descending control
 Opioids / morphine
 Placebo effects
Learning Objectives
 Describe the course of the spinothalamic (and trigeminal) tract(s) from
dermatome to cortex
 Describe the types of fibers carrying pain information, including their
relative conduction velocities, substances they release and where they
terminate in the spinal cord and periphery
 Discuss how the major types of nociceptors respond to damage / injury
 Know that other ascending pathways are involved in pain transmission
 Discuss the descending regulation of noxious information signaling
 Explain how ascending pain information is “gated” in the spinal cord
Dual ascending sensory pathways
 Dorsal columns / ML
 Anterolateral system
 Several distinct pathways
 convey different aspects of
pain - see later
 e.g. spinothalamic awareness and location of
pain
Pain and temperature
Small DRG processes enter the cord:,
Afferents
Lissauer’s
tract
Sub P
Superficial layers
of dorsal horn
Ventral White
Commissure (VWC)
III
synapse in the substantia gelatinosa,
then cross in the VWC and ascend.
Learning Objective #2
Describe the types of fibers carrying pain
information, including their relative
conduction velocities, substances they
release and where they terminate in the
spinal cord and periphery
C fibers use two transmitters:
substance P and glutamate
 Substance P
released with
strong stimuli
 Act to enhance
and prolong the
action of
glutamate acting
on AMPA
receptors
Afferent termination in dorsal horn
 Many nociceptive fibers
terminate in layer I
(marginal layer) and II
(substantia gelatinosa) of
dorsal horn of spinal cord
 Some pain and nonnoxious sensory (e.g.,
proprioception) into other
layers (including ventral
horn - important for
reflexes)
Conduction velocities
 Nociceptive afferents
in peripheral nerve
 Fast sharp pain and
slow dull burning pain
 myelination & axon
diameter
Nociceptors are free nerve endings
Learning Objective #3
Discuss how the major types of
nociceptors respond to damage / injury
Nociceptors
 Harmful stimuli activate nociceptors
 Nociceptors are peripheral free endings of
primary sensory DRG and trigeminal ganglia
neurons
 Membrane contains receptors
 Classes (all located in skin and deep tissues)
 Thermal - extreme temperatures – A fibers
 Mechanical - intense pressure – A fibers - sharp pain
 Polymodal - intense mechanical, chemical or thermal
stimuli – C fibers (unmyelinated) – dull burning
Chemical nociceptors
1. Damaged cells (endothelial / platelets) - release chemicals:
activate & sensitize (HYPERALGESIA)
free nerve endings
2. local & central effects
arachidonic acid
cyclo-oxygenase
(ASPIRIN)
3. vasodilation / extravasation
(neurogenic inflammation)
Thermal nociceptors…
 …..are a separate group
(interestingly including the
heat-sensitive capsaicin
receptor ) and are members of
the transient receptor
potential (TRP) gene family
(non-selective cation channel)
 Activated by extreme temp:
 < 5 C or > 45 C
 Pain & Temperature (STT)
 pictured are “normal”
thermoreceptors (also free
nerve endings)
Mechanical nociceptors……
…….are activated by very strong stimuli
Sensitization of nociceptors
Pain pathways sensitize!!!!!
 After tissue damage, the sensation to pain to subsequent
stimuli is increased at primary site of injury
 Occurs in primary and secondary (surrounding) areas
 Thresholds decrease or magnitude of pain from
suprathreshold stimuli increases - HYPERALGESIA
 Painful response to otherwise innocuous mechanical
stimulus - ALLODYNIA
 With severe persistent injury, C fibers fire repetitively or
“wind up” resulting in increased glutamate release in spinal
cord that activates NMDA receptors – synaptic plasticity
Learning Objective #1
Describe the course of the spinothalamic
(and trigeminal) tract(s) from dermatome
to cortex
Spinothalamic
 Cross
 Direct to multiple
thalamus
Pain pathways through thalamus
 VPL / VPM (neospinothalamic)




receive nociceptive specific and other sensory inputs
spinothalamic tract (STT & TTT)
project to primary somatosensory cortex
neurons have small receptive fields - injury location
 Intralaminar complex (paleospinalthalamic)
 receive nociceptive specific inputs
 Includes projections from the spinoreticulothalamic tract
 diffuse cortical projections
Learning Objective #4
Know that other ascending pathways are
involved in pain transmission
Ascending pain pathways
 Spinoreticular tract; to reticular formation of
pons / medulla (level of attention); and onto
thalamus
 Spinomesencephalic tract; to mesencephalic
reticulum, lateral periqaueductal grey in
midbrain; and on to hypothalamus and limbic
system (emotion and memory integration)
Spinoreticular
 Collaterals - medulla
 Synapses - pons
 Spinoreticulothalamic
tract
Spinomesencephalic
 Synapse - midbrain
 Descending control
Learning Objective #5
Discuss the descending regulation of
noxious information signaling
Descending
control
Direct stimulation of
PAG - specifically
reduces sensation of
pain
Other transmitters
Descending
pathways
can regulate
relay of
nociceptive
information
in the spinal
cord
NA
(opioids)
5-HT
opioids
Local circuit interneurons…..
 …in the spinal cord:
 integration of
ascending and
descending
information to
modulate
nociception
 Placebo effect
Learning Objective #6
Explain how ascending pain information
is “gated” in the spinal cord
Gating control hypothesis of pain
Cortical representation of pain
 VPL / VPM project to primary somatosensory cortex and
then to secondary somatosensory cortex:
 Awareness, location and “intensity” of pain
 Medial thalamus projects to anterior insular cortex:
 Autonomic / visceral component of pain
 Intralaminar nuclei of medial thalamus projects to
anterior cingulate cortex (limbic association cortex):
 Emotional component of pain (circuit of Papez)
Referred pain
Silent nociceptors:
normally not active
but firing threshold
reduced by various
insults
Convergence of somatic and visceral afferents on lamina V