title: Alteration of neuropathic and visceral pain in female C57BL/6J mice lacking the PPAR-α gene.
abstract: BACKGROUND
  Peroxisome proliferator-activated receptors (PPARs) participate in the control of chronic neuropathic and inflammatory pain, and these receptors could play a role on acute pain.
  
  
  OBJECTIVE
  We used null (PPAR-α -/-) and wild-type female mice and the PPAR-α blocker GW6471 to evaluate (1) the role of PPAR-α on neuropathic pain, (2) the involvement of PPAR-α on visceral and acute thermal nociception, and (3) tissue levels of pro-inflammatory factors.
  
  
  METHODS
  Neuropathic pain was induced by sciatic nerve ligature. Acute thermal nociception was evaluated through hot-plate, tail-immersion, and writhing tests. The pro-inflammatory factors nitric oxide, TNF-α, and interleukins-1β and -3 were measured.
  
  
  RESULTS
  Regarding neuropathic pain, higher sensitivity to thermal and mechanical non-noxious and noxious stimuli was observed in mice lacking PPAR-α. Cold and mechanical allodynia and heat hyperalgesia were augmented in null mice. With respect to visceral nociception, writhes after acetic acid were enhanced in mutant mice. Although basal thermal sensitivity was enhanced in PPAR-α -/- mice, cutaneous thermal nociception did not differ between genotypes. Blockade of PPAR-α was devoid of effects on acute thermal and writhing tests. Finally, nerve ligature enhanced pro-inflammatory factors in plantar tissue, levels being higher in null mice. No changes in pro-inflammatory factors were observed in the hot-plate test.
  
  
  CONCLUSIONS
  Genetic ablation of PPAR-α is involved in neuropathic and visceral nociception. Lack of PPAR-α is not involved in acute thermal pain, but it is involved in basal thermal reaction. Changes are biological adaptations to receptor deletion because blockade of PPAR-α does not affect inflammatory pain or thermal reactions.
authors.affiliation: Grup de Recerca en Neurobiologia del Comportament, Universitat Pompeu Fabra, Parc de Recerca Biomèdica, C/Dr. Aiguader 88, 08003 Barcelona, Spain.
authors.forename: Jessica
authors.initials: J
authors.lastname: Ruiz-Medina
authors.forename: Juan A
authors.initials: JA
authors.lastname: Flores
authors.forename: Inmaculada
authors.initials: I
authors.lastname: Tasset
authors.forename: Isaac
authors.initials: I
authors.lastname: Tunez
authors.forename: Olga
authors.initials: O
authors.lastname: Valverde
authors.forename: Emilio
authors.initials: E
authors.lastname: Fernandez-Espejo
mesh_terms: D000818:Animals; D005260:Female; D006930:Hyperalgesia / Q000209:etiology; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D009437:Neuralgia / Q000209:etiology*; D010080:Oxazoles / Q000494:pharmacology; D047493:PPAR alpha / Q000172:deficiency / Q000502:physiology*; D012584:Sciatic Nerve; D014443:Tyrosine / Q000031:analogs & derivatives / Q000494:pharmacology; D059265:Visceral Pain / Q000209:etiology*
chemical_list: C449302:GW 6471; D010080:Oxazoles; D047493:PPAR alpha; D014443:Tyrosine