Increased pain and inflammatory sensitivity in growth hormone-releasing hormone (GHRH) knockout mice

Sheila Leone, Annalisa Chiavaroli, Lucia Recinella, Giustino Orlando, Claudio Ferrante, Guya Diletta Marconi, Irene Gasparo, Alessandra Bitto, Roberto Salvatori, Luigi Brunetti

Research output: Contribution to journalArticlepeer-review

Abstract

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-PGF 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-PGF 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-PGF 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.

Original languageEnglish (US)
Article number106362
JournalProstaglandins and Other Lipid Mediators
Volume144
DOIs
StatePublished - Oct 2019

Keywords

  • Colon
  • Growth hormone-releasing hormone knockout
  • Inflammation
  • Pain

ASJC Scopus subject areas

  • Biochemistry
  • Physiology
  • Pharmacology
  • Cell Biology

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