Attenuation of Visceral and Somatic Nociception by Ghrelin Mimetics.
N Mohammadi. Ehsan E; Louwies. Tijs T; Pietra. Claudio C; Northrup. S Robert SR; Greenwood-Van Meerveld. Beverley B
Key Findings
- Ipamorelin and the brain‑penetrant ghrelin agonist HM01 both reduced visceral (colon) hypersensitivity and somatic mechanical allodynia in rats.
- The pain‑relief was reversed by a ghrelin‑receptor antagonist, confirming the effect is ghrelin‑receptor mediated.
- A peripherally restricted ghrelin mimetic (ipamorelin) was effective, indicating central nervous system penetration isn’t required for the analgesic effect.
Practical Outcomes
- For biohackers, ipamorelin may offer added pain‑relief benefits beyond its growth‑hormone effects, especially for short‑term visceral or somatic discomfort. However, the evidence is limited to animal models, so human dosing, safety, and efficacy remain unproven. Use as an analgesic should be considered experimental and approached with caution.
Summary
In a rat study, the ghrelin‑like drug ipamorelin (which stays mostly outside the brain) and another ghrelin agonist both lowered pain from a stretched colon and from a light poke on the paw. The pain‑blocking effect disappeared when a ghrelin‑receptor blocker was given, proving the effect works through that receptor. This suggests ipamorelin could help with certain types of acute pain, but the findings are still early and only in animals.
Abstract
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. 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. 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. 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.
Study Information
pubmed
2020
2020-08-05T00:00:00.000Z
10.2147/jep.s249747