Growth hormone (GH) and GH-releasing hormone (GHRH), in addition to metabolic and endocrine effects, play a role in the modulation of pain and inflammation. We aimed to elucidate the consequences of GHRH deficiency on acute nociceptive stimulation and on both acute and chronic inflammatory stimuli in a mouse model of GH deficiency. Mice with generalized ablation of the GHRH gene (GHRH knock out, GHRHKO, -/-) were compared to wild type (GHRH +/+) mice. Responsiveness to acute nociceptive stimulation and to acute inflammatory stimulation was evaluated by conventional hot plate apparatus and formalin test, respectively. We also evaluated responsiveness to colonic inflammation induced both in vivo, after dextran sodium sulfate (DSS) treatment, or ex vivo, by incubating colon segments with bacterial lipopolysaccaride (LPS). Macroscopical and histological examinations were performed, prostaglandin (PG) E2 and 8-iso-PGF2α levels and cyclooxigenase (COX)-2 and tumor necrosis factor (TNF)-α gene expression were measured. Compared to controls, -/- mice showed decreased response latency during the hot plate test, and increased licking/biting time in formalin test, particularly in the second phase of inflammation. DSS treated -/- mice showed a significant increase of colonic inflammation compared to controls. Moreover DSS treatment increased PGE2 and 8-iso-PGF2α levels, along with COX-2 and TNF-α gene expression more markedly in colon specimens of -/- mice compared to controls. LPS-induced PGE2 and 8-iso-PGF2α production from colonic segments incubated ex vivo was also increased in -/- mice. Generalized GHRH gene ablation increases sensitivity to thermal pain and both acute and persistent inflammatory stimuli in male mice.

中文翻译：

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生长激素释放激素（GHRH）基因敲除小鼠的疼痛和炎症敏感性增加。

生长激素（GH）和GH释放激素（GHRH）除具有代谢和内分泌作用外，还可以调节疼痛和炎症。我们旨在阐明GHRH缺乏症对GH缺乏症小鼠模型的急性伤害感受性刺激以及急性和慢性炎症刺激的影响。将具有GHRH基因广义消融的小鼠（GHRH基因敲除，GHRHKO，-/-）与野生型（GHRH + / +）小鼠进行比较。分别通过常规热板仪和福尔马林试验评估对急性伤害性刺激和急性炎性刺激的反应性。我们还通过与细菌脂多糖（LPS）一起孵育结肠片段，评估了在葡聚糖硫酸钠（DSS）处理后或离体后对体内引起的结肠炎症的反应性。进行宏观和组织学检查，测量前列腺素（PG）E2和8-异-PGF2α水平以及环氧合酶（COX）-2和肿瘤坏死因子（TNF）-α基因表达。与对照组相比，-/-小鼠在热板试验中显示出降低的反应潜伏期，在福尔马林试验中，尤其是在炎症的第二阶段，其舔/咬时间增加。与对照组相比，经DSS处理的-/-小鼠结肠炎明显增加。此外，与对照组相比，DSS处理在-/-小鼠结肠样本中增加了PGE2和8-iso-PGF2α水平，以及COX-2和TNF-α基因表达。在-/-小鼠中，LPS诱导的离体孵育结肠段的PGE2和8-iso-PGF2α产量也增加。