Molecular mechanisms involved in analgesic effects of 1-deamino-8-D-arginine-vasopressin under thermal exposure and electrocutaneous stimulation in rats

BACKGROUND: The analgesic properties of arginine vasopressin and its synthetic analogue, 1-deamino-8-D-arginine vasopressin, are known. However, it is difficult to use neuropeptides in clinical practice due to the possible development of side effects. The study of the molecular mechanisms and effects of 1-deamino-8-D-arginine-vasopressin in the management of various types of pain will allow us to identify new therapeutic targets and determine the conditions for the safe use of the peptide.

AIM: The study aimed to evaluate the effect of intranasal 1-deamino-8-D-arginine-vasopressin administration on pain sensitivity, the content of monoamines and BDNF in the parietal cortex and spinal cord in thermal and electrocutaneous stimulation in rats.

METHODS: 1-deamino-8-D-arginine-vasopressin was administered intranasally in a thermal pain model at 0.002 µg/day (0.01 µg/course) and 2 µg/day (10 µg/course); 0.02 µg/day (0.1 µg/course) and 2 µg/day (10 µg/course) for electrocutaneous stimulation. Serum corticosterone and brain-derived neurotrophic factor levels in the parietal cortex and spinal cord were determined using enzyme-linked immunosorbent assay. The levels of norepinephrine (NE), dopamine (DA), serotonin (5-HT), and their metabolites, 3,4-dihydroxyphenylacetic acid (DOPAC), homovanillic acid (HVA), and 5-hydroxyindoleacetic acid (5-HIAA), in the brain were determined using high-performance liquid chromatography.

RESULT: 1-deamino-8-D-arginine vasopressin reduced pain sensitivity regardless of the type of pain and doses administered. The involvement of monoamines and brain-derived neurotrophic factor in the analgesic effects depended on the type of exposure and dose of the drug. NE and brain-derived neurotrophic factor at the supraspinal and spinal levels, 5-HT at the spinal cord level have been implicated in analgesia in the thermal pain model.

During electrocutaneous stimulation, DA and 5-HT contributed to analgesia at the supraspinal level; 5-HT, DA and NE at the spinal level. 1-deamino-8-D-arginine-vasopressin did not affect the blood corticosterone in rats with different types of pain.

CONCLUSION: The peptide caused reduced pain sensitivity under various influences. However, this effect in different conditions was due to different neurochemical mechanisms; in thermal pain, it was associated with the modulatory effect of the peptide on monoamine and BDNF levels in the brain or only monoamines in electrocutaneous stimulation.