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

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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.

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Acknowledgments

Supported by grants to EFE from Fundació La Marató TV3 (Barcelona), Plan Andaluz de Investigación (BIO127, Junta de Andalucía), and Ministerio de Sanidad (PNSD, 2009I039). OV was supported by Ministerio de Sanidad (PNSD, 2010) and Generalitat de Catalunya (SGR 2009/684). EFE and OV were supported by Ministerio de Sanidad (RETICS, RD06/001/002 and RD06/0001/1001; Instituto Carlos III, co-financing with FEDER, European Fund for Regional Development), and Ministerio de Ciencia e Innovación and FEDER Funds (BFU2008-01060 to EFE and SAF2010/15793 to OV). The authors thank Dr. Fernando Rodriguez de Fonseca (Fundación IMABIS, Malaga) for the generous gift of PPAR-α null mice.

Disclosure/Conflict of interest

The author(s) declare that, except for income received from my primary employer, no financial support or compensation has been received from any individual or corporate entity over the past three years for research or professional service and there are no personal financial holdings that could be perceived as constituting a potential conflict of interest.

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Authors and Affiliations

  1. Grup de Recerca en Neurobiologia del Comportament, Universitat Pompeu Fabra, Parc de Recerca Biomèdica, C/Dr. Aiguader 88, 08003, Barcelona, Spain

    Jessica Ruiz-Medina & Olga Valverde

  2. Departamento de Fisiología Médica y Biofísica, Universidad de Sevilla, Av. Sanchez Pizjuan 4, 41009, Sevilla, Spain

    Juan A. Flores & Emilio Fernandez-Espejo

  3. Departamento de Bioquímica y Biología Molecular, Universidad de Córdoba, Av. Menendez Pidal s/n, 14004, Cordoba, Spain

    Inmaculada Tasset & Isaac Tunez

Authors
  1. Jessica Ruiz-Medina
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  2. Juan A. Flores
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  3. Inmaculada Tasset
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  4. Isaac Tunez
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  5. Olga Valverde
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  6. Emilio Fernandez-Espejo
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Corresponding authors

Correspondence to Olga Valverde or Emilio Fernandez-Espejo.

Additional information

Olga Valverde and Emilio Fernandez-Espejo equally contributed to this work.

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Ruiz-Medina, J., Flores, J.A., Tasset, I. et al. Alteration of neuropathic and visceral pain in female C57BL/6J mice lacking the PPAR-α gene. Psychopharmacology 222, 477–488 (2012). https://doi.org/10.1007/s00213-012-2662-8

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  • DOI: https://doi.org/10.1007/s00213-012-2662-8

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