TY - JOUR
T1 - Alteration of neuropathic and vi sceral pain in female C57BL/6J mice lacking the PPAR-α gene
AU - Ruiz-Medina, Jessica
AU - Flores, Juan A.
AU - Tasset, Inmaculada
AU - Tunez, Isaac
AU - Valverde, Olga
AU - Fernandez-Espejo, Emilio
N1 - Funding Information:
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 Gen-eralitat 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 (Funda-ción IMABIS, Malaga) for the generous gift of PPAR-α null mice.
PY - 2012/8
Y1 - 2012/8
N2 - 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.
AB - 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.
KW - Allodynia
KW - Hyperalgesia
KW - Neuropathic pain
KW - PPAR-α
KW - Pro-inflammatory factors
KW - Thermal sensitivity
KW - Visceral nociception
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U2 - 10.1007/s00213-012-2662-8
DO - 10.1007/s00213-012-2662-8
M3 - Article
C2 - 22354556
AN - SCOPUS:84864439227
SN - 0033-3158
VL - 222
SP - 477
EP - 488
JO - Psychopharmacology
JF - Psychopharmacology
IS - 3
ER -