Alteration of neuropathic and vi sceral pain in female C57BL/6J mice lacking the PPAR-α gene

Jessica Ruiz-Medina, Juan A. Flores, Inmaculada Tasset, Isaac Tunez, Olga Valverde, Emilio Fernandez-Espejo

Research output: Contribution to journalArticle

15 Scopus citations

Abstract

Rationale 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. Objectives We used null (PPAR-α) andwild-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 proinflammatory 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.

Original languageEnglish (US)
Pages (from-to)477-488
Number of pages12
JournalPsychopharmacology
Volume222
Issue number3
DOIs
StatePublished - Aug 1 2012
Externally publishedYes

Keywords

  • Allodynia
  • Hyperalgesia
  • Neuropathic pain
  • PPAR-α
  • Pro-inflammatory factors
  • Thermal sensitivity
  • Visceral nociception

ASJC Scopus subject areas

  • Pharmacology

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