Coelho S C, Bastos-Pereira A L, Fraga D, Chichorro J G, Zampronio A R
Department of Pharmacology, Federal University of Paraná, Curitiba, Brazil.
Eur J Pain. 2014 Aug;18(7):957-67. doi: 10.1002/j.1532-2149.2013.00441.x. Epub 2014 Jan 7.
This study evaluated the involvement of tumour necrosis factor α (TNF-α) in orofacial thermal and mechanical hyperalgesia induced by an inflammatory stimulus or by chronic constriction of the infraorbital nerve (CION) using etanercept (Eta), a TNF-receptor fusion protein that inhibits TNF-α action.
Animals were treated with Eta (0.5 and 5.0 mg/kg, s.c.) or dexamethasone (Dex, 0.5, 1.0 and 2.0 mg/kg, s.c.) and orofacial thermal (cold and heat) and mechanical hyperalgesia induced by an inflammatory stimulus (carrageenan, Cg 50 and 100 μg/lip) or by chronic CION, a model of neuropathic pain in the orofacial region was evaluated. Treatments with Dex or Eta were carried out before Cg or before or after CION.
Eta or Dex abolished inflammatory thermal and mechanical hyperalgesia. Also, each drug, when given at the day of the surgery and the subsequent day, was effective to abolish thermal and mechanical hyperalgesia induced by CION, assessed on day 4 and on day 13 after the surgery, respectively. However, Eta, but not Dex, given after the CION, abolished thermal and mechanical hyperalgesia and reduced TNF-α level in the trigeminal ganglion.
These results suggest that TNF-α has an important role in cold, heat and mechanical hyperalgesia induced by inflammation or neuropathy in the orofacial region and this may contribute for the establishment of new therapeutic strategies to treat orofacial pain.
本研究使用依那西普(Eta),一种抑制肿瘤坏死因子α(TNF-α)作用的TNF受体融合蛋白,评估TNF-α在由炎症刺激或眶下神经慢性缩窄(CION)诱导的口面部热痛觉过敏和机械性痛觉过敏中的作用。
动物接受Eta(0.5和5.0mg/kg,皮下注射)或地塞米松(Dex,0.5、1.0和2.0mg/kg,皮下注射)治疗,并评估由炎症刺激(角叉菜胶,Cg 50和100μg/唇)或CION(口面部区域神经性疼痛模型)诱导的口面部热(冷和热)痛觉过敏和机械性痛觉过敏。在给予Cg之前或在CION之前或之后进行Dex或Eta治疗。
Eta或Dex消除了炎症性热痛觉过敏和机械性痛觉过敏。此外,每种药物在手术当天和随后一天给药时,分别在手术后第4天和第13天评估,均能有效消除CION诱导的热痛觉过敏和机械性痛觉过敏。然而,在CION后给予Eta而非Dex,可消除热痛觉过敏和机械性痛觉过敏,并降低三叉神经节中的TNF-α水平。
这些结果表明,TNF-α在口面部区域由炎症或神经病变诱导的冷、热和机械性痛觉过敏中起重要作用,这可能有助于建立治疗口面部疼痛的新治疗策略。