Involvement of capsaicin-sensitive afferents and the Transient Receptor Potential Vanilloid 1 Receptor in xylene-induced nocifensive behaviour and inflammation in the mouse

Neurosci Lett. 2009 Feb 27;451(3):204-7. doi: 10.1016/j.neulet.2009.01.016. Epub 2009 Jan 13.


The inflammatory actions of xylene, an aromatic irritant and sensitizing agent, were described to be predominantly neurogenic in the rat, but the mechanism and the role of the Transient Receptor Potential Vanilloid 1 (TRPV1) capsaicin receptor localized on a subpopulation of sensory nerves has not been elucidated. This paper characterizes the involvement of capsaicin-sensitive afferents and the TRPV1 receptor in nociceptive and acute inflammatory effects of xylene in the mouse. Topical application of xylene on the paw induced a short, intensive nocifensive behaviour characterized by paw liftings and shakings, which was more intensive in Balb/c than in C57Bl/6 mice. Genetic deletion of the TRPV1 receptor as well as destroying capsaicin-sensitive nerve terminals with resiniferatoxin (RTX) pretreatment markedly reduced, but did not abolish nocifensive behaviours. In respect to the xylene-induced plasma protein extravasation detected by Evans blue leakage, significant difference was neither observed between the Balb/c and C57Bl/6 strains, nor the ear and the dorsal paw skin. These inflammatory responses were diminished in the RTX pretreated group, but not in the TRPV1 gene-deleted one. Injection of the antioxidant N-acetylcysteine 15min prior to xylene smearing significantly reduced plasma protein extravasation at both sites. These results demonstrate that xylene-induced acute nocifensive behaviour is mediated by capsaicin-sensitive afferents via TRPV1 receptor activation in mice. Neurogenic inflammatory components play an important role in xylene-induced plasma protein extravasation, but independently of the TRPV1 ion channel. Reactive oxygen or carbonyl species participate in this process presumably via stimulation of the TRPA1 channel.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Afferent Pathways / drug effects
  • Afferent Pathways / physiology
  • Animals
  • Behavior, Animal / drug effects
  • Behavior, Animal / physiology
  • Capsaicin / pharmacology
  • Disease Models, Animal
  • Male
  • Mice
  • Mice, Inbred BALB C
  • Mice, Inbred C57BL
  • Mice, Knockout
  • Nerve Tissue Proteins / metabolism
  • Neurogenic Inflammation / chemically induced
  • Neurogenic Inflammation / metabolism
  • Neurogenic Inflammation / physiopathology*
  • Nociceptors / drug effects
  • Nociceptors / physiology*
  • Pain / chemically induced
  • Pain / metabolism
  • Pain / physiopathology*
  • Pain Measurement / drug effects
  • Pain Threshold / drug effects
  • Pain Threshold / physiology
  • Presynaptic Terminals / drug effects
  • Presynaptic Terminals / pathology
  • Sensory Receptor Cells / drug effects
  • Sensory Receptor Cells / physiology*
  • Sensory System Agents / pharmacology
  • TRPV Cation Channels / drug effects
  • TRPV Cation Channels / metabolism*
  • Xylenes / pharmacology


  • Nerve Tissue Proteins
  • Sensory System Agents
  • TRPV Cation Channels
  • TRPV1 protein, mouse
  • Xylenes
  • Capsaicin