Antioxidants Attenuate Acute and Chronic Itch: Peripheral and Central Mechanisms of Oxidative Stress in Pruritus

Neurosci Bull. 2017 Aug;33(4):423-435. doi: 10.1007/s12264-016-0076-z. Epub 2016 Oct 25.


Itch (pruritus) is one of the most disabling syndromes in patients suffering from skin, liver, or kidney diseases. Our previous study highlighted a key role of oxidative stress in acute itch. Here, we evaluated the effects of antioxidants in mouse models of acute and chronic itch and explored the potential mechanisms. The effects of systemic administration of the antioxidants N-acetyl-L-cysteine (NAC) and N-tert-butyl-α-phenylnitrone (PBN) were determined by behavioral tests in mouse models of acute itch induced by compound 48/80 or chloroquine, and chronic itch by treatment with a mixture of acetone-diethyl-ether-water. We found that systemic administration of NAC or PBN significantly alleviated compound 48/80- and chloroquine-induced acute itch in a dose-dependent manner, attenuated dry skin-induced chronic itch, and suppressed oxidative stress in the affected skin. Antioxidants significantly decreased the accumulation of intracellular reactive oxygen species directly induced by compound 48/80 and chloroquine in the cultured dorsal root ganglia-derived cell line ND7-23. Finally, the antioxidants remarkably inhibited the compound 48/80-induced phosphorylation of extracellular signal-regulated kinase in the spinal cord. These results indicated that oxidative stress plays a critical role in acute and chronic itch in the periphery and spinal cord and antioxidant treatment may be a promising strategy for anti-itch therapy.

Keywords: Antioxidants; Extracellular signal-regulated kinase; Itch; Oxidative stress; TRPA1.

MeSH terms

  • Acetylcysteine / therapeutic use
  • Animals
  • Antioxidants / therapeutic use*
  • Cell Line, Transformed
  • Central Nervous System / drug effects*
  • Central Nervous System / metabolism
  • Cyclic N-Oxides / therapeutic use
  • Disease Models, Animal
  • Dose-Response Relationship, Drug
  • Extracellular Signal-Regulated MAP Kinases / metabolism
  • Male
  • Malondialdehyde / metabolism
  • Mice
  • Oxidative Stress / drug effects*
  • Peripheral Nerves / drug effects*
  • Peripheral Nerves / metabolism
  • Pruritus / chemically induced
  • Pruritus / drug therapy*
  • Pruritus / pathology*
  • Reactive Oxygen Species / metabolism
  • Skin / metabolism
  • Superoxide Dismutase / metabolism
  • Time Factors
  • p-Methoxy-N-methylphenethylamine / toxicity


  • Antioxidants
  • Cyclic N-Oxides
  • Reactive Oxygen Species
  • phenyl-N-tert-butylnitrone
  • p-Methoxy-N-methylphenethylamine
  • Malondialdehyde
  • Superoxide Dismutase
  • Extracellular Signal-Regulated MAP Kinases
  • Acetylcysteine