Download ALS Pathway

Neuroanatomy: Pain and Temperature (Walker)
CLASSIC PAIN AND TEMPERATURE PATHWAY (ANTEROLATERAL SYSTEM):
ALS is a crossed spinal pathway that transmits pain, temperature, itch and slow brush (sensual) touch
ALS also known as the lateral spinothalamic tract

First Order Neuron:
o Cell body: in sensory dorsal root ganglion
o Synapse: in dorsal horn of the spinal cord
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Second Order Neuron:
o Cell Body: in dorsal horn
o Path of Axon: project across the midline in the anterior white commissure (crossed axons end up one spinal
level above where they came in); ALS then ascends in the anterior part of the lateral funiciulus

Communicates with the reticular formation along the way (important regulator of autonomic
function with ties to emotional centers of the brain)
o Synapse: ventral posterolateral (VPL) thalamus (diencephalon)
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Third Order Neuron:
o Cell Body: VPL of thalamus
o Synapse: ipsilateral somatosensory cortex (areas 3,1,2) and the insular cortex
FIRST ORDER NEURON: DORSAL ROOT GANGLION
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Function:
o DRG neurons for ALS detect and transmit sensory information from skin and organs except brain tissue
o Act as a sensor of organ homeostasis (informs the spinal cord of the physiological state of tissues); ALS is
the primary alert system for tissue damage
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Example: detects damaging mechanical stress (mechanoreceptors) and temperatures
(thermoreceptors)
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Transmittal Systems for Detecting Tissue Damage (2):
o Aδ Fibers: myelinated for fast sharp pain (short duration)
o C Fibers: unmyelinated for slow burning pain (long duration)

Detecting Pain and Temperature:
o DRG neurons use free nerve endings in the periphery to detect pain and temperature
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Thermoreceptors: detect temperature (sensitive to small changes)
o Warm Receptors: 30-45°C (>45°C activates thermal nocireceptors)
o Cold Receptors: 10-35°C (<10°C turns off these receptors; feel numb)

Note: some cold receptors fire at temperatures >45°C; this provides the paradoxical feeling of
cold if hot probe is place on a small skin region innervated by a cold receptor
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Nocireceptors: detect pain (activated by stimuli that may cause tissue damage)
o Polymodal: non-selective for mechanical, thermal, and chemical stimuli (ie. cannot tell the difference
between the 3); most nocireceptors are of this type
o Unimodal:

Mechanical: selective response to strong pressure

Thermal: selective response to burning heat or extreme cold

Chemical: selective response to histamine or other chemicals

Path of DRG Axons:
o Enter the spinal cord via the lateral division of the dorsal root
o Once in the spinal cord, the fibers ascend and descend (one level up or down) in the posterolateral
fasciculus (Zone of Lissauer); this allows for integration of sensory information at several spinal cord levels

DRG Axon Synapses:
o Synapse in the superficial and deep laminas of the dorsal horn at each respective spinal level

Superficial (Laminas I-II):
 Contain modality specific neurons that respond to specific types of nociceptive or
thermal stimuli
 Contain mechanical slow brush (sensual touch) neurons
 Both fast and slow pain impulses are mediated here

Deep (Lamina III-V):
 Contain neurons that are NOT modality-specific; instead receive convergent input from
multiple nociceptive and thermoceptive fibers
 Also receive mechanoreceptor input carrying proprioceptive information and
descending supraspinal motor information

Neurotransmitters Released by DRG Axons in the Dorsal Horn:
o Glutamate: quick acting, excitatory; likely involved in fast sharp pain
o Substance P: excitatory peptide transmitter; likely involved in slow burning pain

Clinical Correlations:
o Burning sensation when cold hands placed in warm water: polymodal nocireceptors that produce a
burning feeling are normally suppressed by thermoreceptors active at ambient temperatures; when the
temperature gets cold enough, these thermoreceptors are shut off and the nocireceptors can fire pain
signals
o Damaged tissue very sensitive to pain: tissue damage causes hyperalgesia (reduced pain threshold,
increased paint intensity, or spontaneous pain); chemicals like prostaglandins that are released during
damage also stimulate nocireceptors further
o Referred Pain: there is a mixture of visceral and cutaneous nociceptive input onto neurons of the dorsal
horn (creates “neural confusion”); results in nociceptive signals arising from viscera being perceived as pain
from cutaneous regions
o Rubbing helps reduce cutaneous pain: nociceptor activity in the dorsal horn is reduced by the simultaneous
activity of low-threshold mechanoreceptors (Aβ receptors); mediated by inhibitory interneurons of the
dorsal horn that suppress firing of the ALS secondary neuron (gate theory of pain)
SECOND ORDER NEURON: SPINOTHALAMIC NEURON

Cell Body: dorsal horn of the spinal cord

Axons: project across midline through anterior white commissure to form the ALS (ends up one level above where it
entered); ALS ascends in the anterior region of the lateral funiculus
o Somatotopic Organization in the Spinal Cord: cervical, thoracic, lumbar, sacral (from medial to lateral)

Position of ALS in the Brain Stem:
o Medulla: ALS begins to be displaced dorsally and laterally by the inferior olivary nucleus
o Pons: ALS lateral to the medial lemniscus
o Midbrain: ALS shifted dorsolaterally with respect to the ML
o Just Caudal to Diencephalon: ALS and ML fibers mix together as they penetrate the posterior thalamus

ALS Synapse:
o VPL Thalamus: receives somatotopically organized ALS information to provide conscious awareness of
stimuli according to type and location, as well as signals regarding organ and tissue homeostasis
o Reticular Formation: receives ALS (and other pain) information to arouse motor and emotional centers of
the brain, as well as integrate information into autonomic nuclei including the hypothalamus

Damage to ALS Pathway:
o Damage in the lateral funiculus: contralateral loss of pain and temperature perception beginning 1 spinal
level below the location of the lesion (and downward)
o Damage to anterior white commissure (syringomyelia): cavitation of the spinal canal damages the anterior
white commissure producing bilateral loss of pain and temperature perception beginning 1 spinal level
below the cavitation (and downward)
o Damage to ALS in the brainstem: loss of pain and temperature sensation of the contralateral body; some
pain signals will rise to level of consciousness (reticular formation) but localization is lost

Lesion of the dorsolateral medulla (Wallenberg Syndrome): damages the ALS and the spinal
trigeminal system (mediates face pain); this causes a loss of pain and temperature in the
contralateral body, as well as loss of pain and temperature sensation of the ipsilateral face

Damage to VPL Thalamus: results in loss/impairment of all types of sensation on the contralateral side of the body
(ML also terminates in the VPL thalamus); patients also experience spontaneous tearing pain (thalamic pain
syndrome) which cannot be inhibited by routine pain-relievers or morphine (thought to be mediated by the reticular
formation; does respond somewhat to anti-depressant medications)

Surgical Approach to Reducing Chronic Pain:
o Operation can be done to destroy the ALS within the spinal cord (cordotomy)
o Performed several levels above the dermatomal level of agonizing pain and produces immediate
contralateral analgesia
o For many patients, pain returns after several months (because of pain fibers outside of the ALS that ascend
to the brainstem; reticular formation)
THIRD ORDER NEURON: THALAMOCORTICAL NEURON

Cell Body: in the VPL thalamus

Axon: project ALS information to
o Somatosensory cortex (area 3,1,2): ipsilateral projection for conscious awareness; somatotopic
organization discriminates type and location of the stimulus
o
Insular cortex: ipsilateral projection of tissue and organ homeostasis; sometimes called the interoceptive
cortex

Lesions of Somatosensory Cortex:
o Lesions of postcentral gyrus disruopt fine discriminatory functions mediated by ML projections; however,
pain and temperature sensations remain relatively intact
THE EXPERIENCE OF PAIN AND TEMPERATURE- BEYOND THE ALS

Experience of Pain:
Pain can differ from individual to individual, as well as differ in the same individual at different times
o Pain and temperature information is delivered to the reticular formation of the brainstem by way of ALS
collaterals and spinoreticular axons

ALS collaterals give off in the tegmentum of the medulla, pons and midbrain
o Reticular formation relays pain and temperature signals to:

Brainstem autonomic centers and hypothalamus (autonomic and endocrine integration)

Anterior cingulate gyrus and limbic system (emotional integration)

Intralaminar thalamus and basal ganglia (motor integration and arousal)
o Therefore, it is hard to reduce pain by just treating the ALS

Reticular Formation Nuclei Provide Feedback Directly to Dorsal Horn of Spinal Cord:
Allows for regulation of primary DRG input from the periphery
o Descending reticular fibers release serotonin (Raphe nuclei) and NE (Locus ceruleus) into the dorsal horn to
excite enkephalin (opioid) inhibitory interneurons of the substantia gelatinosa (lamina II)
o Part of the endogenous opioid (endorphin) system that naturally suppresses pain input from the periphery
o Example: an athlete that gets injured during a game may not feel pain because of signals from the reticular
fibers that modulate pain signals