De la Luz-Cuellar Yarim Elideth, Rodríguez-Palma Erick Josué, Franco-Enzástiga Úrzula, Déciga-Campos Myrna, Mercado Francisco, Granados-Soto Vinicio
Neurobiology of Pain Laboratory, Departamento de Farmacobiología, Cinvestav, South Campus, Mexico City, Mexico.
Sección de Estudios de Posgrado e Investigación, Escuela Superior de Medicina, Instituto Politécnico Nacional, Mexico City, Mexico.
Brain Res. 2023 Jan 15;1799:148167. doi: 10.1016/j.brainres.2022.148167. Epub 2022 Nov 17.
Fibromyalgia is a complex pain syndrome without a precise etiology. Reduced monoamines levels in serum and cerebrospinal fluid in fibromyalgia patients has been reported and could lead to a dysfunction of descending pain modulatory system producing the painful syndrome. This study evaluated the role of D-like dopamine receptors in the reserpine-induced fibromyalgia-like pain model in female Wistar rats. Reserpine-treated animals were intrathecally injected with different dopamine receptors agonists and antagonists, and small interfering RNAs (siRNAs) against D and D receptor subtypes. Withdrawal and muscle pressure thresholds were assessed with von Frey filaments and the Randall-Selitto test, respectively. Expression of D-like receptors in lumbar spinal cord and dorsal root ganglion was determined using real time polymerase chain reaction (qPCR). Reserpine induced tactile allodynia and muscle hyperalgesia. Intrathecal dopamine and D-like receptor agonist SKF-38393 induced nociceptive hypersensitivity in naïve rats, whilst this effect was prevented by the D-like receptor antagonist SCH-23390. Moreover, SCH-23390 induced a sex-dependent antiallodynic effect in reserpine-treated rats. Furthermore, transient silencing of D and D receptors significantly reduced reserpine-induced hypersensitivity in female rats. Reserpine slightly increased mRNA D receptor expression in dorsal spinal cord, but not in DRG. This work provides new insights about the involvement of the spinal dopaminergic D/D receptors in reserpine-induced hypersensitivity in rats.
纤维肌痛是一种病因不明的复杂疼痛综合征。据报道，纤维肌痛患者血清和脑脊液中的单胺水平降低，这可能导致下行疼痛调节系统功能障碍，从而产生疼痛综合征。本研究评估了D样多巴胺受体在利血平诱导的雌性Wistar大鼠纤维肌痛样疼痛模型中的作用。给利血平处理的动物鞘内注射不同的多巴胺受体激动剂和拮抗剂，以及针对D和D受体亚型的小干扰RNA（siRNA）。分别使用von Frey细丝和Randall-Selitto试验评估撤药和肌肉压力阈值。使用实时聚合酶链反应（qPCR）测定腰脊髓和背根神经节中D样受体的表达。利血平诱导触觉异常性疼痛和肌肉痛觉过敏。鞘内注射多巴胺和D样受体激动剂SKF-38393可诱导未处理大鼠的伤害性超敏反应，而这种作用可被D样受体拮抗剂SCH-23390阻断。此外，SCH-23390在利血平处理的大鼠中诱导了性别依赖性的抗痛觉过敏作用。此外，D和D受体的短暂沉默显著降低了利血平诱导的雌性大鼠超敏反应。利血平使背脊髓中mRNA D受体表达略有增加，但在背根神经节中未增加。这项工作为脊髓多巴胺能D/D受体参与利血平诱导的大鼠超敏反应提供了新的见解。
