title: Over-expression of endothelin-1 in astrocytes, but not endothelial cells, ameliorates inflammatory pain response after formalin injection.
abstract: OBJECTIVE
  Endothelin-1 (ET-1) has been suggested to be involved in different types of pain due to its neuromodulatory nature. However, its role in inflammatory pain processing, specifically the origin-specific effect, has not yet been clearly defined. Therefore, the aim of this study is to determine the role of cell-type specific ET-1 induction in the modulation of inflammatory pain processing.
  
  
  METHODS
  The current study assesses the effects of ET-1 over-expression specifically targeted to astrocytes (GET-1) or endothelial cells (TET-1) on the expression of pain-like behaviors induced by a model of inflammatory pain, consisting of a formalin injection into the hind paw.
  
  
  RESULTS
  The baseline sensitivity thresholds of GET-1 and TET-1 mice to the response elicited by tactile and radiant heat stimulation were similar to those observed in age-matched non-transgenic (NTg) controls. Relative to the NTg controls, GET-1 mice displayed a marked decrease in pain-like behavioral responses during the second phase of formalin-induced pain (i.e., 15-20 min after injection), whereas the responses elicited in TET-1 mice were unaltered. The levels of mRNA encoding adrenomedullin, calcitonin gene-related peptide and calcitonin-like receptor were elevated in the spinal cord of saline-injected GET-1 mice compared to those of NTg mice.
  
  
  CONCLUSIONS
  The current results support a suppressor role for astrocyte-derived ET-1 in inflammatory pain and suggest that the study of GET-1 mice might provide mechanistic insights for improving the treatment of inflammatory pain.
authors: Department of Anaesthesiology, The University of Hong Kong, HKSAR, China.
authors: Victor K L
authors: VK
authors: Hung
authors: Samantha M Y
authors: SM
authors: Chen
authors: Lydia W
authors: LW
authors: Tai
authors: Ann Y S
authors: AY
authors: Chen
authors: Sookja K
authors: SK
authors: Chung
authors: C W
authors: CW
authors: Cheung
mesh_terms: D053607:Adrenomedullin / Q000235:genetics; D000818:Animals; D001253:Astrocytes / Q000378:metabolism*; D001522:Behavior, Animal; D015740:Calcitonin Gene-Related Peptide / Q000235:genetics; D058286:Calcitonin Receptor-Like Protein / Q000235:genetics; D004195:Disease Models, Animal; D042783:Endothelial Cells / Q000378:metabolism; D019332:Endothelin-1 / Q000235:genetics / Q000378:metabolism*; D005557:Formaldehyde / Q000633:toxicity; D005786:Gene Expression Regulation; D007249:Inflammation / Q000503:physiopathology*; D051379:Mice; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D010146:Pain / Q000503:physiopathology*; D012333:RNA, Messenger / Q000378:metabolism; D013116:Spinal Cord / Q000378:metabolism
chemical_list: D058286:Calcitonin Receptor-Like Protein; C545579:Calcrl protein, mouse; D019332:Endothelin-1; D012333:RNA, Messenger; D053607:Adrenomedullin; D005557:Formaldehyde; D015740:Calcitonin Gene-Related Peptide