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PERIPHERAL AXONS: CHARACTERISTICS

Axonal caliber Cutaneous afferents Dorsal root ganglia Muscle spindle Muscle & tendon afferents Motor Nociceptors Thermoreceptors   Temperature-sensitive channels External links   Images   Nerve impulse

CUTANEOUS SENSORY AFFERENT AXONS
Mechanoreceptors: Low Threshold
Name	Stimulus Type	End Organ	Class	Sensation	Trophic Factor
					Survival	Functional
Type I	Displacement	Touch spot	Aαβ	?	?	?
Slow   adapting I	Displacement	Merkel cell	Aαβ	Sustained   pressure	NT3	BDNF
Type II SA II	Displacement	Ruffini	Aαβ	?	?	?
G2 hair	Displacement   velocity	Hair follicle Pallisade ending BNC1 Na+ channel	Aαβ	? Hair   movement	?	?
Rapidly   adapting	Displacement   velocity	Meissner   corpuscle	Aαβ	Tapping	?	?
Field	Displacement   velocity	?	Aαβ	?	?	?
D hair	Displacement   velocity Lowest   mechanothreshold	T-Ca++ channel   (Cav3.2)2	Aδ	?	NT4; NT3 via TrkB	± p75; ?NT4
Pacinian   corpuscle	Displacement   transient   (e.g. vibration)	Pacinian   corpuscle	Aαβ	Buzzing;   Flutter	?	?
G1 hair	Displacement   transient   (e.g. vibration)	Hair follicle	Aαβ	?	?	?
Thermoreceptors
Name	Stimulus Type	End Organ	Class	Sensation	Trophic Factor
					Survival	Functional
Cold	Cooling Menthol	Unmyelinated   neurite complex	Aδ; C	Cool   Innocuous	?	?
Warm	Warming	?	C	Warm   Innocuous	?	?
Also see: Temperature-sensitive channels
Nociceptors
Name	Stimulus Type	End Organ	Class	Sensation	Trophic Factor
					Survival	Functional
Myelinated   nociceptor	Pain	Unmyelinated   Neurite-Schwann   cell complex Basal epidermis Myelinated axons	Aαβ Aδ	Pain   Sharp   Stinging	NGF	p75; NGF
C nociceptor	Inflammation ®   Hyperalgesia	Unmyelinated   axons Project to spinal   Lamina I &   Lamina IIouter	C	Pain   Dull or   Sharp Burn	NGF trkA	p75; NGF; trkA; CGRP; Substance P &   NK1 receptor
	Nerve injury ®   Hyperalgesia	Unmyelinated   axons Project to spinal   Lamina IIinner Noxious heat: TRP-V1	C	Pain   Dull or   Sharp Burn	NGF trkA	GDNF; Ret GFRα; FRAP & TMP; P2X3 ATP   Receptor
	Itch Histamine	Unmyelinated   axons Project to spinal   Lamina I	C	Itch	?	?

MUSCLE SPINDLE INNERVATION (simplified)

Axon caliber

• Related to Neurofilaments
  • Amount: More neurofilaments in larger axons
  • Degree of phosphorylation
    • Decreased phosphorylation: Neurofilaments more densely packed
    • Increased phosphorylation: Side arms spread; Neurofilaments more widely spaced
  • Myelination: Effects on neurofilaments
    • Axons narrower in regions without myelin: Initial segment; Node of Ranvier
    • Unmyelinated axons have more densely packed neurofilaments

Dorsal Root Ganglion

• DRG: Neural crest
  • Time: During early embryogenesis
  • Other neural crest cells: Schwann; Cranial sensory ganglion; Sympathetic & Enteric autonomic
  • DRG cells
    • Initially bipolar
    • Central process grows into root
    • Peripheral process enters segmental nerve
    • Proximal regions of axons eventually coalesce: Forms pseudounipolar configuration
• Perineurial sheath cells: Mesenchymal fibroblasts

• Location: In intervertebral formation; Region where dorsal & ventral roots merge
• DRG ganglion cells
  • Size
    • 10 μM to 100 μM
    • 2 classes: Large clear cells; Small dark cells
  • Location: Clustered around sensory fiber fascicles
  • Proximal axon configuration: Often coiled in glomerulus-like configuration
  • Single ganglion cells may give rise to several peripheral axons
  • Associated with 4 to 6 satellite cells surrounding DRG cell body
  • DRG cells & satellite cells surrounded by basal lamina
• Perineurium & epineurium continuous with dura
  • Region where roots enter spinal canal
  • Traction injuries produce avulsion of roots from cord
• Blood supply
  • From segmental arteries
  • Capillaries in ganglion are fenestrated: Lower barrier to diffusion than blood nerve barrier

• Primary afferents synapse in dorsal gray of spinal cord: Secrete excitatory neurotransmitteers
• Possible neurotransmitters: Numerous
  Glutamate; Aspartate; Substance P; Somatostatin; VIP; Cholecystokinin;
  Angiotensin II; Bombesin; CGRP; Nerve growth factor; Other neurotrophins

• Cutaneous Mechanoreceptors
  • Axons: Large Aβ
  • Termination: Laminae III, IV, V, VI (dorsal)
• Cutaneous Nociceptors
  • Axons: Aδ; C
  • Termination: Laminae I & II
• Temperature: Cold
  • Axons: Aδ; C
  • Neurons
    • Dorsal Root Ganglion: Small; Average cell body diameter 15 μm
    • Lamina I: Pyramidal cells
  • Stimuli
    • Cooling (5°C to 10°C)
    • Menthol
      • Enhances cool sensation of mild low temperatures
      • Receptor: TRPM8
        • Voltage-dependent gating cold-sensitive channel
        • Transient receptor potential (TRP) family
    • Capsaicin: Stimulates cold-sensitive polymodal nociceptors
    • Noxious heat
  • Molecular mechanisms¹
    • Cooling closes a background K⁺ channel
      • Causes depolarization & axonal firing
      • Firing secondarily increases [Ca⁺⁺]_i
      • Identity of specific inhibited K⁺ channel not defined
    • Axonal firing is limited by the slower reduction of a cationic inward current (I_h)
    • Cold-insensitive neurons: Firing is prevented by a slow, transient, 4-AP-sensitive K⁺ current (IK_D)
      • Acts as an excitability brake
      • Pharmacological blockade of IK_D: Induces thermosensitivity in cold-insensitive neurons
    • Cold allodynia: ? Related to down-regulation of (IK_D)
  • Physiology
    • Highly excitable
    • Time-dependent inward rectification during hyperpolarizing current pulses
    • Rebound firing at the end of hyperpolarizing pulses
• Temperature: Heat
  • Axons: C
  • Stimuli: Warming; Capsaicin
  • Capsaicin/Heat receptor: VR1/TRPV1
• Muscle receptors
  • Axons: Aα; Aβ
  • Termination
    • Spindles, primary endings (Aα): Laminae VI; VII
    • Spindles, secondary endings (Aβ): Laminae Iv; V; VI; VII; IX
    • Golgi tendon organs (Aα): Laminae V; VI; VII
• Visceral receptors: Terminate in laminae I & V of spinal cord
• Central terminations
  • Myelinated afferents (Aβ/δ) conveying innocuous mechanoreceptive information: Laminae IIi–V
  • Myelinated afferents (Aβ/δ) conveying noxious mechanoreceptive information: Laminae I & V
  • Unmyelinated afferents, often noxious stimuli: Lamina I & IIo

Temperature Sensing Channels³

Ion channel	Activating temperature	Activators
VRL-1 (TRPV2)	53 °C	Noxious heat
VR1 (TRPV1)	45 °C	Noxious heat Capsaicin pH < 5.9 Vanilloids Endocannabinoids
TRPV3/TRPV4 (VRL-2)	30 to 40 °C	Warm
Painless	> 41 °C	Noxious heat
CMR1/TRPM8	< 25 °C	Cold Menthol
TRPA1 (ANKTM1)	< 17 °C	Noxious cold Icilin
See Transient receptor potential (TRP) channels Pain