Grup de Recerca en Neurobiologia del Comportament, Universitat Pompeu Fabra, Parc de Recerca Biomèdica, C/Dr. Aiguader 88, 08003 Barcelona, Spain.
Psychopharmacology (Berl). 2012 Aug;222(3):477-88. doi: 10.1007/s00213-012-2662-8. Epub 2012 Feb 22.
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.
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.
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.
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.
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.
过氧化物酶体增殖物激活受体 (PPAR) 参与慢性神经性和炎性疼痛的控制，这些受体可能在急性疼痛中发挥作用。
我们使用基因敲除 (PPAR-α -/-) 和野生型雌性小鼠以及 PPAR-α 阻断剂 GW6471 来评估 (1) PPAR-α 在神经性疼痛中的作用，(2) PPAR-α 在内脏和急性热痛觉中的参与，以及 (3) 促炎因子的组织水平。
坐骨神经结扎诱导神经性疼痛。通过热板、尾巴浸泡和扭动试验评估急性热痛觉。测量促炎因子一氧化氮、TNF-α 和白细胞介素-1β 和 -3。
在缺乏 PPAR-α 的小鼠中，对热和机械非伤害性和伤害性刺激的敏感性更高。在突变小鼠中，冷和机械性感觉过敏以及热痛觉过敏增强。对于内脏疼痛，醋酸后扭动增加。尽管 PPAR-α -/- 小鼠的基础热敏感性增强，但基因型之间的皮肤热痛觉没有差异。PPAR-α 阻断对急性热和扭动试验没有影响。最后，神经结扎增强了足底组织中的促炎因子，在突变小鼠中水平更高。在热板试验中没有观察到促炎因子的变化。
PPAR-α 的基因缺失与神经性和内脏疼痛有关。缺乏 PPAR-α 不参与急性热痛，但参与基础热反应。这些变化是对受体缺失的生物学适应，因为 PPAR-α 的阻断不会影响炎症性疼痛或热反应。
