title: Increased function of the TRPV1 channel in small sensory neurons after local inflammation or in vitro exposure to the pro-inflammatory cytokine GRO/KC.
abstract: OBJECTIVE
  Inflammation at the level of the sensory dorsal root ganglia (DRGs) leads to robust mechanical pain behavior and the local inflammation has direct excitatory effects on sensory neurons including small, primarily nociceptive, neurons. These neurons express the transient receptor potential vanilloid-1 (TRPV1) channel, which integrates multiple signals of pain and inflammation. The aim of this study was to characterize the regulation of the TRPV1 channel by local DRG inflammation and by growth-related oncogene (GRO/KC, systemic name: CXCL1), a cytokine known to be upregulated in inflamed DRGs.
  
  
  METHODS
  Activation of the TRPV1 receptor with capsaicin was studied with patch clamp methods in acutely isolated small-diameter rat sensory neurons in primary culture. In vivo, behavioral effects of TRPV1 and GRO/KC were examined by paw injections.
  
  
  RESULTS
  Neurons isolated from lumbar DRGs 3 days after local inflammation showed enhanced TRPV1 function: tachyphylaxis (the decline in response to repeated applications of capsaicin) was significantly reduced. A similar effect on tachyphylaxis was observed in neurons pre-treated for 4 h in vitro with GRO/KC. This effect was blocked by H-89, a protein kinase A inhibitor. Consistent with the in vitro results, in vivo behavioral responses to paw injection of capsaicin were enhanced and prolonged by pre-injecting the paw with GRO/KC 4 h before the capsaicin injection. GRO/KC paw injections alone did not elicit pain behaviors.
  
  
  CONCLUSIONS
  Function of the TRPV1 channel is enhanced by DRG inflammation and these effects are preserved in vitro during short-term culture. The effects (decreased tachyphylaxis) are mimicked by incubation with GRO/KC, which has previously been found to be strongly upregulated in this and other pain models.
authors.affiliation: Pain Research Center, Department of Anesthesiology, University of Cincinnati College of Medicine, Cincinnati, Ohio 45267-0531, USA.
authors.forename: Fei
authors.initials: F
authors.lastname: Dong
authors.forename: Yi-Ru
authors.initials: YR
authors.lastname: Du
authors.forename: Wenrui
authors.initials: W
authors.lastname: Xie
authors.forename: Judith A
authors.initials: JA
authors.lastname: Strong
authors.forename: Xi-Jing
authors.initials: XJ
authors.lastname: He
authors.forename: Jun-Ming
authors.initials: JM
authors.lastname: Zhang
mesh_terms: D000818:Animals; D054360:Chemokine CXCL1 / Q000502:physiology*; D059350:Chronic Pain / Q000209:etiology / Q000378:metabolism / Q000473:pathology; D005260:Female; D005727:Ganglia, Spinal / Q000378:metabolism / Q000473:pathology*; D018836:Inflammation Mediators / Q000502:physiology*; D008297:Male; D018716:Molecular Mimicry / Q000502:physiology; D061251:Primary Cell Culture; D051381:Rats; D017207:Rats, Sprague-Dawley; D011984:Sensory Receptor Cells / Q000473:pathology* / Q000502:physiology; D050916:TRPV Cation Channels / Q000819:agonists / Q000502:physiology*; D013618:Tachyphylaxis / Q000502:physiology
chemical_list: D054360:Chemokine CXCL1; C513297:Cxcl1 protein, rat; D018836:Inflammation Mediators; D050916:TRPV Cation Channels; C493922:Trpv1 protein, rat