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Pain pathway

Y Tang
IASP definition
Pain is an unpleasant sensory and
emotional experience associated
with actual or potential tissue
damage, or described in terms of
such damage.
The pain experience has two
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
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

Anterolateral system
Contains at least 2 pathways:
1. Spinothalamic (a.k.a. direct/neospinothalamic)
pain/temp/crude touch.
2. Spinoreticular (a.k.a.
indirect/paleospinothalamic) suffering
pathway/arousal in response to nociception.
3. Spinomesencephalic pain modulation.
4. Spinotectal initiating eye movement to
painful stimuli.
5. Spinohypothalamic - autonomic and reflex
responses to nociception.
Anterolateral system
Peripheral receptor nerve ending of A and
C-fibres, 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
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
Nerve endings of A and C-fibres
Polymodal mechanical, thermal,
Responds to high threshold stimuli.
First order neuron
Fibre A (myelinated) C
Diameter 2-5 m <2 m
Speed of 5-15 m/s 0.5-2 m/s
Type of pain fast sharp, slow dull ache,
pinprick, burning
noxious heat sensation,
well-localised, diffuse,
short-term. persistent.
Distribution Skin, muscle, Most tissues
First order neuron
A primary afferents terminate in laminae I and
C primary afferents terminate in lamina II
(substantia gelatinosa) and III.
Some 1st order neuron synapse with interneuron
(95% dorsal horn neurones are interneurons-
associated with reflex motor activity).
Axon of interneurons synapse with 2nd order
neurons in laminae V-VIII
Second order neurons
Cell bodies in dorsal horn of spinal
1. Direct spinothalamic
2. Indirect spinomesencephalic,
spinotectal, spinohypothalamic.
2nd order neuron:Spinothalamic
A 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.
2nd order neuron: Spinoreticular
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
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
Terminate in deep layers of superior
For turning upper body, head and
eyes in the direction of painful
2nd order neuron:
spinohypothalamic tract
Ascend to hypothalamus.
Associated with autonomic and reflex
responses to nociception (e.g.
endocrine and cardiovascular).
3rd order neurons
spinothalamic tract
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
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
3rd order neurons
spinoreticular tracts
Signals transmitted from reticular
formation to intralaminar nuclei of
thalamus, hypothalamus, limbic
Hypothalamus-autonomic and reflex.
Pain to face and head
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,
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

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
Postcentral gyrus of parietal lobe
Brodmanns 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

Downloaded from www.spinacare.wordpress.com.

Secondary somatosensory
cortex S-II
At parietal operculum, ceiling of
lateral sulcus.
Brodmanns area 43.
Function in memory of sensory input
and sensory integration.
Other brain areas related to
From electroencephalography (EEG),
functional MRI (fMRI),
magnetoencephalography (MEG), positron
emission tomography (PET).
Anterior cingulate cortex (ACC), anterior
insular cortex, supplemental area of motor
ACC and anterior insular cortices
connected to limbic cortex.
Visceral pain
Visceral organs themselves have no pain receptors.
Pain receptors embedded in walls of arteries serving
these organs.
Diffuse, poorly localised, referred to another somatic
Nociceptive signals follow same pathway as signals
from somatic structures.
Receptors: free nerve endings or Pacinian corpuscles.
First order neurons: C, A or A fibres.
Respond to stretching, or ischaemia.
Second order neurons: spinothalamic and
spinoreticular tract.
Modulation of nociception
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 (A 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
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, beta-endorphin and
Descending pathway
Descending pathway
PAG main descending inhibitory
control on the gate mechanism in
the dorsal horn. Has abundance opioid
receptors and peptides. Connections
1. Nucleus raphe nucleus (serotonergic)
inhibitory interneurones.
2. Locus coeruleus (Noradrenergic)
dorsal horn.
Pain pathway examples
Pain pathway in labour
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
2nd stage labour (pain sharp)
direct pressure by the presenting
part on vagina and perineum
Stimulation of pudendal nerve (S2-4).
A fibres carry impulse via pudendal
nerve (S2-4) spinothalamic tract
somatosensory cortex.
Pain pathway in labour
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
Higher block level (T4) due to
peritoneal manipulation.
Pain pathway cornea
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

Taken from Greys Anatomy.