Attenuation of Visceral and Somatic Nociception by Ghrelin Mimetics.
This animal study investigated whether ghrelin receptor agonists (ghrelin mimetics) could reduce visceral and somatic pain in the absence of active inflammation. Using a rat model, researchers induced non-inflammatory visceral hypersensitivity by infusing dilute acetic acid into the colon, and somatic mechanical allodynia was also assessed. Two ghrelin receptor agonists were tested: HM01, a centrally and peripherally active compound administered orally, and ipamorelin, a peripherally restricted compound administered intravenously. Pain responses were measured by counting abdominal muscle contractions during colorectal distension (visceral pain) and paw withdrawals to von Frey filament stimulation (somatic pain). The study found that both HM01 and ipamorelin significantly reduced colonic hypersensitivity and somatic allodynia compared to vehicle controls. These effects were reversed by co-administration of the ghrelin receptor antagonist H0900, confirming that the anti-nociceptive effects were receptor-mediated. Notably, the peripherally restricted compound ipamorelin was effective, suggesting peripheral ghrelin receptor activation may be sufficient. The study is limited by its exclusive use of an animal model, meaning translational relevance to humans remains unestablished. The authors propose ghrelin mimetics as a potential novel approach for treating acute visceral and somatic pain.
Why this grade: All experiments were conducted exclusively in rats; no human subjects or clinical data were included, limiting direct applicability to human pain conditions.
Purpose The anti-nociceptive properties of ghrelin have been demonstrated in alleviating inflammatory and neuropathic pain. Whether a ghrelin receptor-mediated mechanism attenuates visceral and somatic pain in the absence of active inflammation remains to be explored. Here, we investigate the efficacy of peripherally restricted (ipamorelin) and a globally active (HM01) selective ghrelin receptor agonist in an experimental model of non-inflammatory visceral hypersensitivity and somatic mechanical allodynia. Materials and methods Visceral hypersensitivity was induced by dilute acetic acid (0.6%) infusion in the colon of rats in the absence of colonic epithelial inflammation. Ghrelin mimetics HM01 and ipamorelin were administered orally or intravenously, respectively. The ghrelin receptor antagonist H0900 was administered orally. Colonic sensitivity was assessed via a visceromotor behavioral response (VMR) quantified as the number of abdominal contractions in response to graded isobaric pressures (0-60 mmHg) of colorectal distension (CRD). Somatic mechanical allodynia was quantified by the number of ipsilateral paw withdrawals in response to a calibrated von Frey filament. Results Compared to vehicle controls, ghrelin mimetics HM01 and ipamorelin significantly attenuated colonic hypersensitivity and somatic allodynia. The anti-nociceptive effects of the ghrelin mimetics were blocked after administration of the ghrelin receptor antagonist H0900. Conclusion We have shown that ghrelin receptor-mediated mechanisms are involved in visceral and somatic hypersensitivity in the absence of active colonic inflammation. Furthermore, visceral and somatic hypersensitivity could be attenuated by a peripherally restricted ghrelin mimetic. These results highlight a potential novel approach for treating acute visceral and somatic pain by ghrelin mimetics.
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