Dental School, International Branch of Shahid Beheshti University of Medical Sciences.
School of Pharmacy.
Behav Pharmacol. 2020 Aug;31(5):500-509. doi: 10.1097/FBP.0000000000000531.
Involvement of the ventral tegmental area (VTA) and the lateral hypothalamus (LH) in the modulation of formalin-induced nociception is well documented. In this study, we investigated the role of orexin 1 (OX1) and orexin 2 (OX2) receptors within the VTA in modulation of the LH-induced antinociception during both phases of orofacial formalin test. Male adult Wistar rats weighing 230-250 g were unilaterally implanted with two stainless steel guide cannulae in the VTA and LH. In two separate supergroups, animals received SB334867 (OX1 receptor antagonist) or TCS OX2 29 (OX2 receptor antagonist), at the doses of 3, 10, and 30 nM/rat into the VTA before intra-LH microinjection of carbachol (250 nM/rat) as a nonselective cholinergic receptor agonist for chemical stimulation of orexinergic neurons in this region. Rats were subcutaneously injected with 1% formalin (50 µl; s) into the orofacial region, 5 min after intra-LH microinjection of carbachol or saline. The blockade of both orexin receptors in the VTA reduced intra-LH carbachol-induced antinociception. However, this effect was greater during the late phases of the orofacial formalin test. The blockade of the OX1 but not OX2 receptors in the VTA affect the pain-related behaviors during the early phase, and also, the contribution of OX2 receptor to modulate the LH-induced antinociceptive responses was greater than OX1 receptor during the late phase of orofacial formalin test. The results indicated the neural pathway projected from the LH to the VTA contributes to the modulation of formalin-induced orofacial pain. Orexinergic drugs might be considered as therapeutic agents for inflammatory pain treatment.
腹侧被盖区（VTA）和外侧下丘脑（LH）参与了福尔马林诱导的疼痛的调制，这一点已得到充分证实。在这项研究中，我们研究了 VTA 内的食欲素 1（OX1）和食欲素 2（OX2）受体在口腔福尔马林测试的两个阶段中对 LH 诱导的抗伤害作用的调制作用。雄性成年 Wistar 大鼠体重为 230-250g，单侧植入 VTA 和 LH 中的两个不锈钢引导套管。在两个单独的超组中，动物在 VTA 内接受 SB334867（OX1 受体拮抗剂）或 TCS OX2 29（OX2 受体拮抗剂），剂量为 3、10 和 30nM/大鼠，然后在 LH 内微注射卡巴胆碱（250nM/大鼠）作为一种非选择性胆碱能受体激动剂，用于化学刺激该区域的食欲素能神经元。在 LH 内微注射卡巴胆碱或生理盐水后 5 分钟，将 1%福尔马林（50μl；s）皮下注射到口腔区域。VTA 中两种食欲素受体的阻断均减少了 LH 内卡巴胆碱诱导的抗伤害作用。然而，这种效应在口腔福尔马林测试的后期阶段更为明显。VTA 中 OX1 受体而不是 OX2 受体的阻断会影响早期阶段的疼痛相关行为，并且 OX2 受体对调节 LH 诱导的抗伤害反应的贡献在口腔福尔马林测试的后期阶段大于 OX1 受体。结果表明，从 LH 投射到 VTA 的神经通路有助于调节福尔马林诱导的口腔疼痛。食欲素能药物可能被认为是治疗炎症性疼痛的治疗剂。
