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腹外侧导水管周围灰质的外源性和内源性组胺通过阿片受体减轻坐骨神经慢性缩窄损伤诱导的神经性疼痛。

Ventrolateral periaqueductal gray exogenous and endogenous histamine attenuates sciatic nerve chronic constriction injury-induced neuropathic pain through opioid receptors.

作者信息

Salimi Sara, Tamaddonfard Esmaeal, Soltanalinejad-Taghiabad Farhad

机构信息

PhD Candidate, Department of Basic Sciences, Faculty of Veterinary Medicine, Urmia University, Urmia, Iran.

Department of Basic Sciences, Faculty of Veterinary Medicine, Urmia University, Urmia, Iran.

出版信息

Vet Res Forum. 2021 Dec;12(4):429-436. doi: 10.30466/vrf.2019.112474.2679. Epub 2021 Dec 15.

Abstract

The aim of the present study was to investigate the effects of intra-ventrolateral periaqueductal gray (vlPAG) microinjection of histamine and thioperamide (a histamine H receptor antagonist/inverse agonist) on neuropathic pain. To explore the possible mechanism, naloxone was microinjected alone or in combination with histamine and thioperamide. Neuropathic pain was induced by the left sciatic nerve chronic constriction injury. Both the right and left sides of vlPAG of the brain were surgically cannulated. Cold allodynia and mechanical hyperalgesia were recorded by acetone evaporation and von Frey filament tests. Areas under curve of allodynia and hyperalgesia were calculated. Histamine (0.50 and 2.00 µg per site), thioperamide (4.00 µg per site) and thioperamide (4.00 µg per site) before histamine (2.00 µg per site) suppressed cold allodynia and mechanical hyperalgesia after microinjection into the vlPAG. Microinjection of naloxone (0.25 and 1.00 µg per site) into the vlPAG had no effect on cold allodynia and mechanical hyperalgesia. The anti-allodynic and anti-hyperalgesic effects induced by microinjection of histamine (2.00 µg per site) and thioperamide (4.00 µg per site) into the vlPAG were inhibited by prior microinjection of naloxone (1.00 µg per site) into the same site. The above-mentioned agents did not alter locomotor activity. Based on our present results, it was concluded that exogenous (by histamine microinjection) and endogenous (by thioperamide microinjection) histamine of the vlPAG might contribute to the descending pain control mechanisms through a naloxone-sensitive mechanism.

摘要

本研究的目的是探讨向脑室内侧导水管周围灰质(vlPAG)微量注射组胺和硫代哌啶醇(一种组胺H受体拮抗剂/反向激动剂)对神经性疼痛的影响。为探究可能的机制,单独或联合组胺和硫代哌啶醇微量注射纳洛酮。通过左侧坐骨神经慢性压迫损伤诱导神经性疼痛。手术将大脑双侧的vlPAG插管。通过丙酮蒸发试验和von Frey细丝试验记录冷觉异常和机械性痛觉过敏。计算异常性疼痛和痛觉过敏的曲线下面积。向vlPAG微量注射组胺(每部位0.50和2.00μg)、硫代哌啶醇(每部位4.00μg)以及组胺(每部位2.00μg)前的硫代哌啶醇(每部位4.00μg)可抑制冷觉异常和机械性痛觉过敏。向vlPAG微量注射纳洛酮(每部位0.25和1.00μg)对冷觉异常和机械性痛觉过敏无影响。预先向同一部位微量注射纳洛酮(每部位1.00μg)可抑制向vlPAG微量注射组胺(每部位2.00μg)和硫代哌啶醇(每部位4.00μg)所诱导的抗异常性疼痛和抗痛觉过敏作用。上述药物不改变运动活性。根据我们目前的结果,得出结论:vlPAG的外源性组胺(通过微量注射组胺)和内源性组胺(通过微量注射硫代哌啶醇)可能通过一种纳洛酮敏感机制促进下行性疼痛控制机制。

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