Lyons Danielle N, Zhang Liping, Danaher Robert J, Miller Craig S, Westlund Karin N
Departments of *Physiology, College of Medicine †Oral Health Practice, University of Kentucky, Lexington, KY.
Clin J Pain. 2017 Dec;33(12):1071-1080. doi: 10.1097/AJP.0000000000000509.
The aim of this study is to investigate the role of peroxisome proliferator-activated receptor-gamma isoform (PPARγ), in trigeminal neuropathic pain utilizing a novel mouse trigeminal inflammatory compression (TIC) injury model.
The study determined that the PPARγ nuclear receptor plays a significant role in trigeminal nociception transmission, evidenced by: 1) Intense PPARγ immunoreactivity is expressed 3 weeks after TIC nerve injury in the spinal trigeminal caudalis, the termination site of trigeminal nociceptive nerve fibers. 2) Systemic administration of a PPARγ agonist, pioglitazone (PIO), attenuates whisker pad mechanical allodynia at doses of 300 mg/kg i.p. and 600 mg/kg p.o. 3) Administration of a PPARγ antagonist, GW9662 (30 mg/kg i.p.), prior to providing the optimal dose of PIO (300 mg/kg i.p.) blocked the analgesic effect of PIO.
This is the first study localizing PPARγ immunoreactivity throughout the brainstem trigeminal sensory spinal nucleus (spV) and its increase three weeks after TIC nerve injury. This is also the first study to demonstrate that activation of PPARγ attenuates trigeminal hypersensitivity in the mouse TIC nerve injury model. The findings presented here suggest the possibility of utilizing the FDA approved diabetic treatment drug, PIO, as a new therapeutic that targets PPARγ for treatment of patients suffering from orofacial neuropathic pain.
本研究旨在利用一种新型小鼠三叉神经炎性压迫（TIC）损伤模型，探讨过氧化物酶体增殖物激活受体γ亚型（PPARγ）在三叉神经病理性疼痛中的作用。
该研究确定PPARγ核受体在三叉神经伤害性感受传递中起重要作用，证据如下：1）在三叉神经伤害性神经纤维的终末部位——三叉神经尾侧脊髓核中，TIC神经损伤3周后可检测到强烈的PPARγ免疫反应性。2）全身给予PPARγ激动剂吡格列酮（PIO），腹腔注射剂量为300 mg/kg和口服剂量为600 mg/kg时，可减轻触须垫机械性异常性疼痛。3）在给予最佳剂量的PIO（腹腔注射300 mg/kg）之前，给予PPARγ拮抗剂GW9662（腹腔注射30 mg/kg）可阻断PIO的镇痛作用。
这是第一项在整个脑干三叉神经感觉脊髓核（spV）定位PPARγ免疫反应性及其在TIC神经损伤3周后增加的研究。这也是第一项证明在小鼠TIC神经损伤模型中激活PPARγ可减轻三叉神经超敏反应的研究。此处呈现的研究结果表明，有可能将FDA批准的糖尿病治疗药物PIO用作一种针对PPARγ的新疗法，用于治疗患有口面部神经性疼痛的患者。
