Salehi Sakineh, Kashfi Khosrow, Manaheji Homa, Haghparast Abbas
Department of Physiology, School of Medicine, Shahid Beheshti University of Medical Sciences, Tehran, Iran.
Department of Molecular, Cellular and Biomedical Sciences, Sophie Davis School of Biomedical Education, City University of New York School of Medicine, NY, USA.
Brain Res. 2020 Apr 1;1732:146674. doi: 10.1016/j.brainres.2020.146674. Epub 2020 Jan 22.
To date several circuities in supraspinal site of the central nervous system have been known to engage in pain modulation. Lateral hypothalamus (LH) is known as part of the circuit of pain modulation among supraspinal sites. Its role in several animal pain models has been well defined. In this study, we examined the role of spinal orexin receptors in antinociceptive response elicited by the LH stimulation in an animal model of neuropathic pain. Male Wistar rats were unilaterally implanted with a cannula into the LH and a catheter into the L4-L5 segments of the spinal cord followed by chronic constriction injury (CCI) surgery. Intra-LH microinjection of carbachol (500 nM; 0.5 μL) was done 5 min after intrathecal administration of the orexin receptor antagonists, SB-334867 or TCS OX2 29; control animals received DMSO. Mechanical allodynia and thermal hyperalgesia were evaluated using von Frey filaments and a thermal stimulus. The results showed that carbachol induces antiallodynic and anti-thermal hyperalgesic effects in a dose-dependent manner. The antiallodynic and anti-thermal hyperalgesic effects induced by intra-LH injection of carbachol were reversed by intrathecal administration of 10 μL-100 nM solutions of SB-334867 or TCS OX2 in neuropathic rats. However, solely intrathecal administration of both antagonists had no effect in neuropathic rats. There appears to be a neural pathway from the LH to the spinal cord, which potentially contributes to the modulation of neuropathic pain. The implications are that there may be novel therapeutic approaches for the treatment of people suffered from chronic neuropathic pain in clinic.
迄今为止，已知中枢神经系统脊髓上部位的几种神经回路参与疼痛调节。外侧下丘脑（LH）是脊髓上部位疼痛调节回路的一部分。其在多种动物疼痛模型中的作用已得到充分明确。在本研究中，我们在神经性疼痛动物模型中研究了脊髓中食欲素受体在LH刺激引发的抗伤害感受反应中的作用。雄性Wistar大鼠单侧植入一根套管至LH，并在脊髓L4 - L5节段插入一根导管，随后进行慢性压迫损伤（CCI）手术。在鞘内注射食欲素受体拮抗剂SB - 334867或TCS OX2 29后5分钟，向LH内微量注射卡巴胆碱（500 nM；0.5 μL）；对照动物注射二甲基亚砜（DMSO）。使用von Frey细丝和热刺激评估机械性异常性疼痛和热痛觉过敏。结果表明，卡巴胆碱以剂量依赖性方式诱导抗异常性疼痛和抗热痛觉过敏作用。在神经性大鼠中，鞘内注射10 μL - 100 nM的SB - 334867或TCS OX2可逆转LH内注射卡巴胆碱所诱导的抗异常性疼痛和抗热痛觉过敏作用。然而，仅鞘内注射这两种拮抗剂对神经性大鼠无效。似乎存在一条从LH到脊髓的神经通路，这可能有助于调节神经性疼痛。这意味着临床上可能存在治疗慢性神经性疼痛患者的新治疗方法。
