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ITCH (Pruritis)¹

Itch: Anatomy & Physiology

• Peripheral Stimuli
  • General
    • Itch axons may be mechanically insensitive or sensitive
    • Mustard oil: Stimulates distinct axons conveying dysesthesias associated with itch
  • Histamine
    • Onset: Delay of 30 to 60 seconds
    • Maximum: 2 to 3 minutes
    • Duration: 10 minutes
    • Afferents: Mechanoinsensitive C-fibers
      • Extensive branching in skin
      • Endings probably located in deeper skin layers
    • Only small inhibition by capsaicin
    • Itch associated with Flare response
      • Correlation between itch intensity & flare area
  • Non-histaminergic mechanisms³
    • May be stimulated by spicules from the plant Mucuna pruriens (Cowhage)
      • Mediated by mucunain cysteine protease: Activates PAR2
      • Activates polymodal C-fibers (mechano/heat sensitive)
    • Time course: Decline over 10 minutes
    • Inhibition: Desensitization with capsaicin; No effect of anti-histamine
    • No associated flare response: Vasodilation only in specific area of stimulus
    • No correlation in magnitude of itch stimulated by histamine & cowhage
• Primary itch afferents
  • C-fibers
  • Physiology
    • Transcutaneous electrical threshhold: High
    • Conduction velocity: Low
    • Mechanical stimuli: Unresponsive
    • Histamine sensitive
  • May be associated with VR1/TRPV1 channels (Capsaicin/Heat receptor)
  • Itch: Gastrin-releasing peptide (GRP; Bombesin)⁴
    • Expressed in subset of small and medium-sized dorsal root ganglion neurons
    • Colocalized with: Peripherin, CGRP, Substance P, TRPV1
    • Spinal cord fibers: Lamina I & II outer layer
    • GRP receptor mutant (reduced function) mice
      • Reduced response to pruritogenic agents: 48/80; PAR2 agonist (SLIGRL-NH2); Chloroquine
      • No change in pain responses
      • Mechanism: Reduced itch probably related to histamine-independent itch pathway
• Secondary itch afferents
  • Location of cell bodies: Lamina I of spinal dorsal grey
  • Projection pathway
    • Spinothalamic tract
    • Conduction velocity of axons: Slow
  • Termination: Thalamic nuclei
    • Ventral posterior inferior (VPI)
    • Periphery of Ventral posterior lateral (vVPL)
  • Inhibited by painful stimuli

Itch: Clinical Syndromes

• Dermatologic: Dermatoses (Atopic dermatitis); Surface irritants (Fiberglass, wool, foreign bodies, insect bites)
• Renal disease: Chronic; Especially during or after dialysis
• Liver disease: Obstructive biliary disease, Cholestasis
• Infection: HIV; Trichinosis; Onchocerciasis, Echinococcosis; Hepatitis C; Chicken pox
• Focal nerve lesions
  • Post-Herpetic neuralgia (48%): Especially on face & head
  • Trigeminal trophic syndrome: Especially after Gasserian ganglion ablation
  • Cheiralgia paresthetica
  • Brachioradial pruritis: Dorsolateral arm; C5-C8 lesions
  • Notalgia paresthetica: T2-T6 lesions
• Opioid administration: Systemic; Spinal
• CNS: Multiple sclerosis
• Endocrine: Hyperparathyroidism; Diabetes mellitus
• Iron deficiency anemia
• Pruritis ani²
• Other drugs
  • Allergic reactions: Penicillin, Sulfa drugs
  • Vasoactive drugs: Nicotinic acid, caffeine, alcohol
  • CNS drugs: Morphine, cocaine, amphetamines, codeine
  • Chloroquine
• Malignancy: Hodgkin's disease, Polycythemia rubra vera, Leukemia, Mycosis fungoides,
    Sézary syndrome, Visceral neoplasia, Carcinoid, Multiple myeloma
• Pregnancy

Itch: Systemic treatment

• Treatment of underlying condition
• H1-blockers: Diphenhydramine; Hydroxyzine
• H2-blockers: Cimetidine; Ranitidine
• Tricyclic antidepressants: Doxepin; Amitriptyline
• Anticonvulsants: Gabapentin; Dilantin
• Danazole
• Prednisone