| First Author | Ruiz-Medina J | Year | 2012 |
| Journal | Psychopharmacology (Berl) | Volume | 222 |
| Issue | 3 | Pages | 477-88 |
| PubMed ID | 22354556 | Mgi Jnum | J:327443 |
| Mgi Id | MGI:6881988 | Doi | 10.1007/s00213-012-2662-8 |
| Citation | Ruiz-Medina J, et al. (2012) Alteration of neuropathic and visceral pain in female C57BL/6J mice lacking the PPAR-alpha gene. Psychopharmacology (Berl) 222(3):477-88 |
| abstractText | 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-alpha -/-) and wild-type female mice and the PPAR-alpha blocker GW6471 to evaluate (1) the role of PPAR-alpha on neuropathic pain, (2) the involvement of PPAR-alpha 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-alpha, and interleukins-1beta 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-alpha. 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-alpha -/- mice, cutaneous thermal nociception did not differ between genotypes. Blockade of PPAR-alpha 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-alpha is involved in neuropathic and visceral nociception. Lack of PPAR-alpha 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-alpha does not affect inflammatory pain or thermal reactions. |
