Anterolateral System of Ascending Pathways

Overview

1. Pain
2. Thermal sensations (both warm and cold)
3. Crude touch and pressure - capable only of crude localizing ability on the body surface
4. Tickle and itch sensations
5. Sexual sensations

Anatomy of the Anterolateral Pathway

• Signals from nociceptors, thermoreceptors, and crude mechanoreceptors travel via small, thinly myelinated (Aδ) and unmyelinated (C) fibers to the spinal cord through the dorsal roots.

• The anterolateral pathway fibers originate mainly from dorsal horn laminae I, IV, V, and VI - the zones where the relevant dorsal root sensory fibers terminate after entering the cord.

• The axons of second-order neurons cross immediately in the anterior commissure of the spinal cord to the opposite (contralateral) anterior and lateral white columns.
• This is a key contrast with the dorsal column system, which ascends ipsilaterally and crosses only at the medulla.

• After crossing, fibers ascend as two named tracts:
  • Lateral spinothalamic tract - primarily carries pain and temperature
  • Anterior spinothalamic tract - primarily carries crude touch and pressure

1. Reticular nuclei of the brainstem - especially relevant for pain signals
2. Two thalamic complexes:
   • Ventrobasal complex (VPL nucleus) - receives mainly tactile signals from the anterolateral path and relays them to the somatosensory cortex (same target as dorsal column signals)
   • Intralaminar nuclei - receives most pain signals (relayed from brainstem reticular nuclei)

Cortical Projections and Functional Components

• Primary somatosensory cortex (S1) and secondary somatosensory cortex (S2) - contralateral side
• Cingulate gyrus - contralateral
• Amygdala, frontal lobe, insular cortex

Characteristics of Transmission (Guyton & Hall, Ch. 48)

Somatotopic Organization

• Sacral fibers are positioned most laterally
• Cervical fibers are positioned most medially

Effects of Lesions

• Damage to the ventrolateral spinothalamic pathway → contralateral loss of pain and temperature sensation below the level of the lesion.
• Dorsal column damage → ipsilateral loss of touch, vibration, and proprioception below the lesion.

• Thalamic lesions → can cause thalamic pain syndrome (Déjerine-Roussy) during recovery - characterized by chronic burning pain contralateral to the side of the infarct.
• Primary somatosensory cortex damage → does not abolish somatic sensation but impairs ability to localize noxious stimuli in time, space, and intensity; irritation causes contralateral paresthesia.
• Cingulate cortex damage → impairs recognition of the aversive nature of a noxious stimulus.

Summary Comparison: Anterolateral vs. Dorsal Column Systems

• Guyton and Hall Textbook of Medical Physiology, 14th Ed., Ch. 48 (Sensory Transmission; Anterolateral System)
• Ganong's Review of Medical Physiology, 26th Ed., Ch. 8 (Somatosensory Pathways; Ventrolateral Spinothalamic Tract; Effects of CNS Lesions)

Pain Modulation Pathways: Descending Controls and Gate Control Theory

1. Gate Control Theory (Spinal Level)

The Basic Concept

• Activation of large-diameter, low-threshold mechanoreceptor afferents (Aα and Aβ fibers) - which carry innocuous touch and vibration - sends collaterals into the dorsal horn.
• The activity of these large-fiber afferents reduces the responsiveness of dorsal horn neurons to input from nociceptive afferents (Aδ and C fibers).
• The large fibers in effect "close the gate" on pain transmission before it can ascend.

Cellular Mechanism in the Dorsal Horn

• Opioid receptors on the terminals of nociceptive fibers (and in the dorsal root ganglia)
• Opioid binding → decreased Ca²⁺ influx → reduced duration of action potential → decreased transmitter (glutamate + neuropeptides) release from the nociceptive terminal

• Opioid receptors on dendrites of dorsal horn projection neurons
• Opioid binding → increased K⁺ conductance → hyperpolarization of the dorsal horn neuron → decreased response to excitatory synaptic input
• Also reduces amplitude of the EPSP produced by nociceptor stimulation

2. Descending Pain Modulation (Supraspinal Control)

The Three-Component Analgesia System

• Periaqueductal gray (PAG) matter surrounding the aqueduct of Sylvius in the mesencephalon and upper pons
• Periventricular nuclei of the hypothalamus, adjacent to the third ventricle
• Medial forebrain bundle (hypothalamus)
• These areas receive higher cortical influences and are the starting point of the descending cascade

• PAG and periventricular neurons send signals to:
  • Raphe magnus nucleus - a thin midline nucleus in the lower pons/upper medulla (serotonergic)
  • Nucleus reticularis paragigantocellularis - located laterally in the medulla (catecholaminergic)
• Electrical stimulation of the PAG or raphe magnus nucleus can suppress many strong pain signals entering via dorsal spinal roots

• Second-order signals descend via the dorsolateral columns of the spinal cord
• They reach a pain inhibitory complex in the dorsal horns
• Here, analgesia signals block pain before it is relayed to the brain

Neurotransmitters in the Descending System

The Brain's Opiate System - Endorphins and Enkephalins

• Pro-opiomelanocortin → β-endorphin (found in hypothalamus and pituitary)
• Proenkephalin → met-enkephalin and leu-enkephalin (found in brainstem and spinal cord, within the analgesia system)
• Prodynorphin → dynorphin (same areas as enkephalins, lower quantities)

3. Inhibition by Tactile Signals (Peripheral Gate)

• Why rubbing skin near a painful area brings relief
• Why liniments work for pain relief
• The mechanism behind acupuncture - both psychogenic excitation of the central analgesia system and activation of Aβ fibers contribute
• The basis of TENS (transcutaneous electrical nerve stimulation)

4. Stress-Induced Analgesia

• Release of norepinephrine (from brainstem catecholaminergic neurons) in the amygdala - which mediates the motivational-affective responses to pain
• Release of endogenous cannabinoids (2-arachidonylglycerol/2AG and anandamide), acting on CB1 receptors (euphoria, analgesia) and CB2 receptors (expressed on activated microglia in neuropathic pain states, reducing inflammatory response)

5. Clinical Correlates and Applications

Summary Diagram of the Full System

Cortex / Limbic system
        ↓
Periventricular nuclei (hypothalamus)
        ↓  [enkephalin]
Periaqueductal Gray (PAG) - midbrain
        ↓
Nucleus Raphe Magnus (pons/medulla)         Locus Coeruleus (pons)
[serotonergic]                               [noradrenergic]
        ↓ dorsolateral columns                      ↓
Dorsal Horn (spinal cord)
  ↑ [large Aβ fiber input - gate control]
  Enkephalin interneurons
  → Presynaptic inhibition of C/Aδ terminals (↓ Ca²⁺ → ↓ glutamate/neuropeptide release)
  → Postsynaptic inhibition of dorsal horn neurons (↑ K⁺ → hyperpolarization)
        ↓ BLOCKED
Pain signal does NOT ascend spinothalamic tract

• Guyton and Hall Textbook of Medical Physiology, 14th Ed., Ch. 49 (Pain Suppression/Analgesia System; Endorphins and Enkephalins; Inhibition by Tactile Signals)
• Ganong's Review of Medical Physiology, 26th Ed., Ch. 8 (Processing Information in the Dorsal Horn - Gate Control; Roles of PAG and Brainstem; Stress-Induced Analgesia)