Pain pathway
Y Tang
IASP definition
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“Pain is an unpleasant sensory and
emotional experience associated with
actual or potential tissue damage, or
described in terms of such damage.”
Pain
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The pain experience has two dimensions:
1. Sensory/discriminative - allowing us
to locate tissue damage
2. Affective/aversive - ‘unpleasant’ and
‘emotional’ in the IASP definition. Avoid
stimuli that can damage tissue.
Pain pathway
Ascending pain pathway
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Those responsible for pain are called
anterolateral system (also relays crude
touch and temperature).
Dorsal column-medial lemniscal pathway mainly fine
touch, vibration and position.
Somatosensory to cerebellum mainly for
proprioception.
Anterolateral system
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2.
3.
4.
5.
Contains at least 2 pathways:
Spinothalamic (a.k.a. direct/neospinothalamic) –
pain/temp/crude touch.
Spinoreticular (a.k.a.
indirect/paleospinothalamic) –’suffering
pathway’/arousal in response to nociception.
Spinomesencephalic –pain modulation.
Spinotectal –initiating eye movement to painful
stimuli.
Spinohypothalamic - autonomic and reflex
responses to nociception.
Anterolateral system
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Peripheral receptor – nerve ending of Aδ and Cfibres, detect stimulus. Signal carried by:
1st order neuron – from periphery to spinal
cord. Cell body in dorsal root ganglion, may
travel up or down in ipsilateral spinal cord for
several segments in the dorsolateral fasciculus
(Lissauer tract), and then turn deeply to end in
the dorsal horn. Then synapse with:
Anterolateral system
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2nd order neuron – cell body in dorsal horn.
Decussates in anterior white commisure to the
contralateral cord. Axons of spinothalamic tract
ascend all the way to terminate in the thalamus.
The other two tracts terminate at brainstem
levels. Then synapse with:
3rd order neuron – cell body in thalamus,
ascend ipsilaterally to project to somatosensory
cortex.
Ascending pathway. See handout.
Peripheral receptor (Nociceptor)
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Nerve endings of Aδ and C-fibres (80%)
Polymodal –mechanical, thermal,
chemical.
Responds to high threshold stimuli.
First order neuron
Fibre
Aδ (myelinated)
C (unmyelinated)
Diameter
2-5 μm
<2 μm
Speed of
conduction
Type of pain
5-15 m/s
0.5-2 m/s
‘fast’ sharp,
pinprick, noxious
heat
well-localised,
short-term.
Skin, muscle, joint
‘slow’ dull ache,
burning sensation,
diffuse, persistent.
Distribution
Most tissues
First order neuron
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Aδ primary afferents terminate in laminae I and
V.
C primary afferents terminate in lamina II
(substantia gelatinosa) and III.
Some 1st order neuron synapse with interneuron
(95% dorsal horn neurones are interneuronsassociated with reflex motor activity).
Axon of interneurons synapse with 2nd order
neurons in laminae V-VIII
Second order neurons
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1.
2.
Cell bodies in dorsal horn of spinal cord.
Direct –spinothalamic
Indirect –spinomesencephalic,
spinotectal, spinohypothalamic.
2nd order neuron:Spinothalamic
tract
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Aδ fibres.
15% nociceptive fibers from spinal cord terminate
directly in thalamus via spinothalamic tract.
Consists of 2 anatomically distinct tracts; lateral (sharp
pain and temp) and anterior spinothalamic tract (crude
touch). Recent studies show all tracts in anterolateral
system transmit nociceptive signals.
Projections to ventral posterior lateral nucleus of
thalamus (also ventral posterior inferior and intralaminar
nuclei).
Also has collaterals to reticular formation.
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2nd order neuron: Spinoreticular
tract
C fibres.
Some fibers decussate to contralateral side via anterior
commisure, many ascend ipsilaterally.
Transmit nociceptive, thermal, crude touch signals from
spinal cord to thalamus indirectly by forming multiple
synapses in the reticular formation prior to their thalamic
projections.
Some second order neurons bypass reticular formation
and relay sensory input from C fibres directly to
intralaminar nuclei of thalamus.
Reticular formation sends signals not only to thalamus
but to hypothalamus (autonomic and reflex response),
and the limbic system (mediate emotional component of
nociception).
2nd order neuron:
spinomesencephalic tract
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Fibres terminate in periaqueductal grey matter
and the midbrain raphe nuclei, both which give
rise to fibres that modulate nociceptive
transmission (‘descending pain-inhibiting
system’).
Some other fibres terminate in parabrachial
nucleus, which then sends fibres to amygdala
(component of limbic system associated with
processing of emotions).
2nd order neuron: spinotectal tract
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Terminate in deep layers of superior
colliculus.
For turning upper body, head and eyes in
the direction of painful stimulus.
2nd order neuron:
spinohypothalamic tract
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Ascend to hypothalamus.
Associated with autonomic and reflex
responses to nociception (e.g. endocrine
and cardiovascular).
3rd order neurons –spinothalamic
tract
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Cell bodies in thalamus.
ventral posterior lateral, ventral posterior inferior
and intralaminar thalamic nuclei.
Ventral posterior lateral nucleus gives fibres to
posterior limb of internal capsule and corona
radiata. Terminate in primary somatosensory
cortex S-I (postcentral gyrus). Also sends fibres
to secondary somatosensory cortex S-II.
3rd order neurons –spinothalamic
tract
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Ventral posterior inferior nucleus projects mostly
to S-II but some to S-I.
Intralaminar nuclei projects to striatum (ie
caudatae nucleus and putamen), S-I and S-II,
cingulate gyrus and prefrontal cortex.
(Most nociception relaying fibres arriving at
intralaminar nuclei transmit nociceptive
information relayed there from reticular
formation (have multiple synapses before
arriving)).
3rd order neurons –spinoreticular
tracts
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Signals transmitted from reticular
formation to intralaminar nuclei of
thalamus, hypothalamus, limbic system.
Hypothalamus-autonomic and reflex.
Limbic-emotional/’suffering’.
Pain to face and head
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Trigeminal nerve 3 branches:
Ophthalmic (V1) –scalp and forehead, upper eyelid,
conjunctiva, cornea, nose, nasal mucosa, frontal sinus,
meninges.
Maxillary (V2) –lower eyelid, cheeks, nares, upper lip,
upper teeth/gums, nasal mucosa, palate and roof of
pharynx, maxillary/ethmoid/sphenoid sinuses, meninges.
Mandibular (V3) – lower lip, lower teeth and gums, chin,
and jaw (except angle), parts of external ear and
meninges, mouth (not taste).
* V1 and V2 pure sensory, V3 mixed sensory and motor.
Pain to face and head
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1st order neuron carried by trigeminal nerve (cell
body in Trigeminal/ Gasserian ganglion) enter
pons, descend to medulla forming the spinal
trigeminal tract and synapse in spinal trigeminal
nucleus (caudal part) 2nd order neurons cross
midline and ascend as trigeminothalamic tract 
VPM thalamus  3rd order neurons to sensory
cortex
Pain pathway
Primary somatosensory cortex S-I
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Postcentral gyrus of parietal lobe
Brodmann’s areas 3a,3b,1,2.
Processing of pain localisation, intensity,
quality, and sensory integration at
conscious level.
Also sends signals to secondary
somatosensory cortex.
Sensory homunculus
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Downloaded from www.spinacare.wordpress.com.
Secondary somatosensory cortex SII
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At parietal operculum, ceiling of lateral
sulcus.
Brodmann’s area 43.
Function in memory of sensory input and
sensory integration.
Other brain areas related to pain
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From electroencephalography (EEG), functional
MRI (fMRI), magnetoencephalography (MEG),
positron emission tomography (PET).
Anterior cingulate cortex (ACC), anterior insular
cortex, supplemental area of motor cortex.
ACC and anterior insular cortices connected to
limbic cortex.
Visceral pain
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Visceral organs themselves have no pain receptors. Pain
receptors embedded in walls of arteries serving these
organs.
Diffuse, poorly localised, ‘referred’ to another somatic
structure.
Nociceptive signals follow same pathway as signals from
somatic structures.
Receptors: free nerve endings or Pacinian corpuscles.
First order neurons: C, Aδ or Aβ fibres.
Respond to stretching, or ischaemia.
Second order neurons: spinothalamic and spinoreticular
tract.
Modulation of nociception
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Gate control theory of pain
Impulses flow from periphery to brain through a
‘gate’ at spinal level.
Site at substantia gelatinosa (lamina II) where
pain is modulated.
Small nerve fibers (C fibres) and large nerve
fibers (Aβ fibres) synapse with: projection cells,
which go up the spinothalamic tract to the brain,
and inhibitory interneurons within the dorsal
horn.
Gate control theory
Descending pathway
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Not as well understood as ascending one.
Originate at cortex, thalamus and brainstem
(Periaqueductal grey; raphe nuclei and locus
coeruleus).
Relay stations in brainstem.
Main neurotransmitters: noradrenaline, serotonin
and endogenous opioids (enkephalin, betaendorphin and dynorphin).
Descending pathway
Descending pathway
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2.
PAG –main descending inhibitory control
on the ‘gate’ mechanism in the dorsal
horn. Has abundance opioid receptors
and peptides. Connections with:
Nucleus raphe nucleus (serotonergic) 
inhibitory interneurones.
Locus coeruleus (Noradrenergic) 
dorsal horn.
Pain pathway examples
Pain pathway in labour
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Stage 1 labour (pain poorly localised)
Due to uterine (visceral) contractions and
stretching cervix.
Sensation carried by mainly C-fibres 
inferior, middle and superior hypogastric
plexus  travel with sympathetic chain
associated with dorsal rami of T10-L1
spinal nerves referred visceral pain.
Pain pathway in labour
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2nd stage labour (pain sharp)
direct pressure by the presenting part on
vagina and perineum
Stimulation of pudendal nerve (S2-4).
Aδ fibres carry impulse via pudendal nerve
(S2-4)  spinothalamic tract 
somatosensory cortex.
Pain pathway in labour
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Other pain sensitive structures in the pelvis are
also involved, i.e. the adnexi, the pelvic parietal
peritoneum, bladder, urethra, rectum and the
roots of the lumbar plexus.
Therefore L2 to S5 must also be blocked. There
is an overlap and pain relief is not a simple
matter of blocking T10 to L1 for the first stage
and S2, 3, 4 for the second stage of labour.
Caesarean section
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Higher block level (T4) due to peritoneal
manipulation.
Pain pathway cornea
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Cornea  long ciliary nerves (also has sympathetic
fibres) and short ciliary nerves (also has parasympathetic
fibres +/- sympathetic)nasociliary nerve ophthalmic
division trigeminal nerve (V1) (cell body in Trigeminal/
Gasserian ganglion) enter pons, descend to medulla
forming the spinal trigeminal tract and synapse in spinal
trigeminal nucleus (caudal part) 2nd order neurons
cross midline and ascend as trigeminothalamic tract 
VPM thalamus  3rd order neurons to sensory cortex
*note sensory to conjunctiva:lacrimal branch V1 ,
vision:optic nerve.
Pain pathway -Cornea
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Taken from Grey’s Anatomy.