Changes in the nociceptive response to thermal stimulation in rats following administration of N-terminal analogs of the adrenocorticotropic hormone

Dodonova SA1, Bobyntsev II1, Belykh AE1, Andreeva LA2, Myasoedov NF2
About authors

1 Kursk State Medical University, Kursk, Russia

2 Institute of Molecular Genetics, Moscow, Russia

Correspondence should be addressed: Svetlana А. Dodonova
K. Marx, 3, Kursk, 305004; ur.liam@atevsavonodod

About paper

Author contribution: Dodonova SA, Belykh AE — collected processed and analyzed the data; Bobyntsev II, Andreeva LA, Myasoedov NF — conceived and designed the study; Dodonova SA, Belykh AE, Bobyntsev II — wrote this manuscript.

Received: 2019-12-02 Accepted: 2019-12-16 Published online: 2019-12-21

Melanocortins (MCs) are an increasingly studied class of regulatory peptides exerting a wide range of biological effects. All naturally occurring MCs share a His-Phe-Arg-Trp fragment (HFRW) corresponding to the sequence of amino acid residues 6–9 of the adrenocorticotropic hormone (ACTH6-9), which is also a central active component of ACTH. Attaching the Pro-Gly-Pro (PGP) sequence to the C-end of the peptide extends the duration of the peptide’s effect. The aim of this study was to investigate the effects of ACTH6-9-PGP (HFRWPGP) on the spinal and supraspinal mechanisms involved in the nociceptive response in rats and to compare them to those of its structural analog ACTH4-7-PGP (MEHFPGP). ACTH6-9-PGP effects were studied following the intraperitoneal administration of the peptide at doses 0.5, 1.5, 5, 15, 50, 150, or 450 μg/kg 15 minutes before the hot plate and tail flick tests. ACTH4-7-PGP effects were studied under the same conditions at the following doses: 50, 150 and 450 μg/kg. We found that ACTH6-9-PGP administered intraperitoneally at 5 or 150 μg/kg induced a pronounced reduction in pain sensitivity 15 and 45 minutes after the injection (p = 0.04); this effect was implemented via supraspinal mechanisms. In the tail flick test, 150 μg/kg ACTH6-9-PGP increased pain sensitivity, with the participation of segmental spinal mechanisms (p = 0.04). ACTH4-7-PGP did not have any effect on the studied mechanisms of pain sensitivity. Thus, unlike ACTH4-7-PGP, ACTH6-9-PGP can both increase pain sensitivity and exert an analgesic effect.

Keywords: pain, regulatory peptide, ACTH, hot plate, tail flick