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

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 -/-) 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: Jessica Ruiz-Medina, Juan A Flores, Inmaculada Tasset, Isaac Tunez, Olga Valverde, Emilio Fernandez-Espejo
• Journal: Psychopharmacology (Psychopharmacology (Berl)) Vol. 222 Issue 3 Pg. 477-88 (Aug 2012) ISSN: 1432-2072 [Electronic] Germany
• PMID: 22354556 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• GW 6471
• Oxazoles
• PPAR alpha
• Tyrosine

Topics

• Animals
• Female
• Hyperalgesia (etiology)
• Mice
• Mice, Inbred C57BL
• Mice, Knockout
• Neuralgia (etiology)
• Oxazoles (pharmacology)
• PPAR alpha (deficiency, physiology)
• Sciatic Nerve
• Tyrosine (analogs & derivatives, pharmacology)
• Visceral Pain (etiology)