GHRP-6
Growth Hormone Releasing Peptide-6, Growth hormone-releasing hexapeptide, His-D-Trp-Ala-Trp-D-Phe-Lys-NH2
The gastrointestinal hormone ghrelin modulates inhibitory neurotransmission in deep laminae of mouse spinal cord dorsal horn.
Vergnano. Angela M AM; Ferrini. Francesco F; Salio. Chiara C; Lossi. Laura L; Baratta. Mario M; Merighi. Adalberto A
Key Findings
- GHSR is present and functional in mouse spinal dorsal horn neurons.
- Ghrelin (via GHSR) dramatically increases the frequency and size of inhibitory GABA/glycine currents in about 60% of recorded neurons.
- The effect depends on action potentials and is blocked by a GHSR antagonist, confirming receptor specificity.
- Ghrelin reduces activity markers (c‑fos) in pain‑related spinal neurons, indicating antinociceptive action.
Practical Outcomes
- For biohackers, this hints that GHRP-6 could be explored as a potential analgesic, especially for inflammatory or neuropathic pain, but the evidence is limited to mouse spinal tissue and indirect. Any self‑experiment should start with low doses, monitor pain perception, and consider central nervous system effects, keeping in mind the lack of human data.
Summary
The study shows that activating the ghrelin receptor (GHSR) in the spinal cord of mice boosts inhibitory signals (GABA and glycine), which can dampen pain signals. This suggests that drugs like GHRP-6, which also turn on GHSR, might have pain‑relieving effects beyond their usual use for growth hormone release.
Abstract
Ghrelin is mainly described for its effects on feeding behavior and metabolism. However, central nervous system distribution of its receptor [type 1a GH secretagogue receptor (GHSR)] and modulation of neurotransmission in the hypothalamus suggest broader effects than originally predicted. Systemically administrated ghrelin inhibits inflammatory pain after behavioral observations. Therefore, we investigated the expression and function of type 1a GHSR in mouse spinal cord by molecular biology, biochemistry, histology, and electrophysiology. The mRNA and protein were detected in tissue extracts by RT-PCR and Western blotting. In situ, receptor mRNA and immunoreactivity were localized to cell bodies within the medial aspect of the deep dorsal horn. Patch clamp recordings on laminae IV-VI demonstrated that bath-applied ghrelin (100 nm) induced a strong increase of spontaneous gamma-aminobutyric acid/glycine-mediated current frequency (463 +/- 93% of the control) and amplitude (150 +/- 16% of the control) in about 60% of recorded neurons. Specificity of type 1a GHSR activation was confirmed by the lack of effect of the deacylated form of ghrelin (des-acyl-ghrelin) and after preincubation with the specific receptor antagonist [d-Lys(3)]GHRP-6. In the presence of tetrodotoxin, the effect of the peptide was strongly reduced, mainly indicating an action potential-dependent mechanism. The functional link between ghrelin and pain was confirmed by inhibition in vitro of the c-fos response to capsaicin activation of nociceptive fibers, after quantification of Fos-immunoreactive nuclei in laminae IV-VI. Our results are the first demonstration of the presence of functional type 1a GHSRs in the spinal cord and indicate that ghrelin may exert antinociceptive effects by directly increasing inhibitory neurotransmission in a subset of deep dorsal horn neurons.
Study Information
pubmed
2008
2008-01-17T00:00:00.000Z
10.1210/en.2007-1164
41
35