Ghrelin inhibits inflammatory pain in rats: Involvement of the opioid system

Sibilia, V.; Lattuada, N.; Rapetti, D.; Pagani, F.; Vincenza, DeLuca; Bulgarelli, Ilaria; Locatelli, Vittorio; Guidobono, F.; Netti, C.

doi:10.1016/j.neuropharm.2006.04.009

Cited by 80 publications

(57 citation statements)

References 39 publications

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“…Ghrelin down-regulates proinflammatory cytokine release in rats, and this effect is mediated by the vagus nerve (19,28). By interacting with the opioid system, ghrelin inhibits inflammatory pain in rats (29).…”

Section: Discussionmentioning

confidence: 99%

Bacterial Endotoxin Induces Biphasic Changes in Plasma Ghrelin in Healthy Humans

Vila

Maier

Riedl

et al. 2007

The Journal of Clinical Endocrinology &Amp; Metabolism

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Context:Ghrelin is a gut hormone with a highly preserved biological activity, which seems not to be restricted to the regulation of food intake, body composition, and growth. Continuous research is unraveling new properties of ghrelin, among others cardiovascular and antiinflammatory activities. Ghrelin is recently implicated in the host response to bacterial endotoxin in rodents and suggested as a possible therapeutic tool in sepsis.Objective: This study aimed to investigate plasma ghrelin levels during human bacterial endotoxemia. Design and Setting:We conducted a randomized, placebocontrolled, crossover clinical trial at a university medical center.Study Participants: Participants included 10 healthy men. Intervention:After an overnight fast, study subjects were randomized to 2 ng/kg Escherichia coli endotoxin [lipopolysaccharide (LPS)] or placebo and monitored for 6 h. Main Outcome Measures:We measured ghrelin, GH, ACTH, cortisol, glucose, free fatty acids, TNF-␣, IL-6, and IL-1 receptor antagonist.Results: LPS administration induced a rapid ghrelin surge at 120 min (⌬ ghrelin 100.2 Ϯ 30.3 vs. 7.2 Ϯ 26.4 pg/ml on the placebo day, P ϭ 0.042). This ghrelin peak occurred 30 min after the TNF-␣ peak and corresponded with IL-6, GH, and ACTH peaks. Starting from 120 min and thereafter, ghrelin continuously decreased, reaching a nadir at 5 h after LPS administration (⌬ ghrelin, Ϫ43.8 Ϯ 28.4 compared with 70.3 Ϯ 38.2 pg/ml on the control days, P ϭ 0.038). Conclusions:Ghrelin is one of the first hormones rapidly increasing in the human physiological response to bacterial endotoxic shock. Plasma ghrelin might be part of the complex immuno-neuroendocrine mechanisms activated by systemic infection and inflammation in humans.

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Section: Discussionmentioning

confidence: 99%

Bacterial Endotoxin Induces Biphasic Changes in Plasma Ghrelin in Healthy Humans

Vila

Maier

Riedl

et al. 2007

The Journal of Clinical Endocrinology &Amp; Metabolism

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“…There is, e.g., a possibility that stimulation of the GHS-R increases opioid tone in the brain. Sibilia et al found that ICV ghrelin-induced hyperalgesia is sensitive to central naltrexone treatment (Sibilia et al, 2006). Although the results of pain-related experiments cannot be considered as conclusive evidence explaining feeding phenomena, they clearly indicate the necessity to study this possible interaction also in relation to food intake control.…”

Section: Ghrelin and The Reward Systemmentioning

confidence: 99%

Ghrelin in the CNS: From hunger to a rewarding and memorable meal?

Olszewski

Schiöth

Levine

2008

Brain Research Reviews

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Ghrelin, the endogenous agonist of the growth hormone secretagogue receptor, has been shown to induce robust feeding responses in numerous experimental models. Although ghrelin comes from both peripheral and central sources, its hyperphagic properties, to a large extent, arise from activity at the brain level. The current review focuses on describing central mechanisms through which this peptide affects consumption. We address the issue of whether ghrelin serves just as a signal of energy needs of the organism or -as suggested by the most recent findings -also affects food intake via other feeding-related mechanisms, including reward and memory. Complexity of ghrelin's role in the regulation of ingestive behavior is discussed by characterizing its influence on consumption, reward and memory as well as by defining its function within the brain circuitry and interplay with other neuropeptides. Keywordsghrelin; food intake; reward; energy; brain Ghrelin and its receptor: the beginningsBowers et al. discovered synthetic peptides that stimulated and amplified the release of growth hormone (GH) by acting at the hypothalamus and the pituitary (Bowers et al., 1980;Bowers et al., 1984). Their GH hypophysiotropic activity was distinct from the action of growth hormone releasing hormone (GHRH) and it was GHRH-independent. They were classified as growth hormone-releasing peptides (GHRPs) and growth hormone secetagogues (GHSs) (for review, see (Smith, 2005)).

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“…Interestingly, there is a delicate interaction between ghrelin and opioid systems. Ghrelin interacts with opioid receptors to regulate the mesolimbic dopaminergic system, which is associated with food reward [20] and the antihyperalgesic effect of ghrelin is reversed by the MOR antagonist, naloxone [17]. …”

Section: Introductionmentioning

confidence: 99%

Antinociceptive Effect of Ghrelin in a Rat Model of Irritable Bowel Syndrome Involves TRPV1/Opioid Systems

Mao

Chen

et al. 2017

Cell Physiol Biochem

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Background/Aims: Irritable bowel syndrome (IBS), defined as recurrent abdominal pain and changes in bowel habits, seriously affects quality of life and ability to work. Ghrelin is a brain-gut hormone, which has been reported to show antinociceptive effects in peripheral pain. We investigated the effect of ghrelin on visceral hypersensitivity and pain in a rat model of IBS. Methods: Maternal deprivation (MD) was used to provide a stress-induced model of IBS in Wistar rats. Colorectal distension (CRD) was used to detect visceral sensitivity, which was evaluated by abdominal withdrawal reflex (AWR) scores. Rats that were confirmed to have visceral hypersensitivity after MD were injected with ghrelin (10 µg/kg) subcutaneously twice a week from weeks 7 to 8. [D-Lys3]-GHRP-6 (100 nmol/L) and naloxone (100 nmol/L) were administered subcutaneously to block growth hormone secretagogue receptor 1α (GHS-R1α) and opioid receptors, respectively. Expression of transient receptor potential vanilloid type 1 (TRPV1) and µ and κ opioid receptors (MOR and KOR) in colon, dorsal root ganglion (DRG) and cerebral cortex tissues were detected by western blotting, quantitative real-time polymerase chain reaction (qRT-PCR), immunohistochemical analyses and immunofluorescence. Results: Ghrelin treatment increased expression of opioid receptors and inhibited expression of TRPV1 in colon, dorsal root ganglion (DRG) and cerebral cortex. The antinociceptive effect of ghrelin in the rat model of IBS was partly blocked by both the ghrelin antagonist [D-Lys3]-GHRP-6 and the opioid receptor antagonist naloxone. Conclusion: The results indicate that ghrelin exerted an antinociceptive effect, which was mediated via TRPV1/opioid systems, in IBS-induced visceral hypersensitivity. Ghrelin might potentially be used as a new treatment for IBS.

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Ghrelin inhibits inflammatory pain in rats: Involvement of the opioid system

Cited by 80 publications

References 39 publications

Bacterial Endotoxin Induces Biphasic Changes in Plasma Ghrelin in Healthy Humans

Bacterial Endotoxin Induces Biphasic Changes in Plasma Ghrelin in Healthy Humans

Ghrelin in the CNS: From hunger to a rewarding and memorable meal?

Antinociceptive Effect of Ghrelin in a Rat Model of Irritable Bowel Syndrome Involves TRPV1/Opioid Systems

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