Effect of vasopressin on pain sensitivity, monoamine levels, and brain-derived neurotrophic factor in rats in the early period after vital stress

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Abstract

BACKGROUND: At present, studying the mechanisms that potentiate or prevent posttraumatic stress disorder is of particular relevance, as it may help identify new therapeutic approaches. Arginine vasopressin is known to be involved in the modulation of stress and pain responses. However, the effects of this peptide on pain sensitivity and related biochemical mechanisms in a posttraumatic stress disorder model have not been studied.

AIM: The work aimed to evaluate the effects of the synthetic vasopressin analog 1-deamino-8-D-arginine vasopressin (DDAVP) on pain sensitivity, serum corticosterone concentration, brain-derived neurotrophic factor (BDNF) levels, and monoamine content in the parietal cortex and spinal cord in rats during the acute period after vital stress.

METHODS: The study included 41 male Wistar rats. All animals were divided into four groups: five intact rats (control), 12 rats receiving DDAVP, 12 rats exposed to vital stress induced by a single experience of witnessing the death of a partner caused by a predator (tiger python), and 12 rats receiving DDAVP on days 1–5 after vital stress. DDAVP was administered intranasally at a single dose of 2 μg and a cumulative dose of 10 μg. BDNF levels in the parietal cortex and spinal cord, as well as serum corticosterone concentration, were determined using enzyme-linked immunosorbent assay. Levels of norepinephrine (NE), serotonin (5-HT), dopamine (DA), and their metabolites in the brain were measured by high-performance liquid chromatography.

RESULTS: DDAVP administration produced an analgesic effect, accompanied by increased BDNF and NE levels and decreased homovanillic acid (HVA) levels in the sensorimotor cortex. In the spinal cord, DDAVP increased BDNF levels and reduced NE, 5-HT, and 3,4-dihydroxyphenylacetic acid (DOPAC) content. On day 5 after vital stress, rats demonstrated reduced pain sensitivity along with elevated blood corticosterone levels; in the sensorimotor cortex, NE levels increased and HVA levels decreased; in the spinal cord, NE and DOPAC levels decreased. In stressed rats, DDAVP increased pain sensitivity, elevated blood corticosterone levels, increased BDNF, NE, and DA levels in the parietal cortex, and reduced NE, DA, and DOPAC levels in the spinal cord.

CONCLUSION: The analgesic effect of DDAVP was associated with elevated BDNF levels and altered NE and DA metabolism in the sensorimotor cortex and spinal cord, as well as with changes in 5-HT content in the spinal cord. On day 5 after vital stress, rats developed analgesia, which involved glucocorticoid mechanisms and NE and DA signaling at both cortical and spinal cord levels. DDAVP administration during the acute period after vital stress induced hyperalgesia in rats, correlating with increased BDNF levels in the sensorimotor cortex and the involvement of noradrenergic and dopaminergic systems at cortical and spinal cord levels.

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About the authors

Aleksandra A. Nikitina

Institute of Experimental Medicine

Author for correspondence.
Email: doknikitina@yandex.ru
ORCID iD: 0009-0009-7481-6620
SPIN-code: 5649-2050
Russian Federation, Saint Petersburg

Svetlana G. Belokoskova

Institute of Experimental Medicine

Email: Belokoskova.sg@iemspb.ru
ORCID iD: 0000-0002-0552-4810
SPIN-code: 4317-6620

MD, Dr. Sci. (Medicine)

Russian Federation, Saint Petersburg

Dmitrii S. Traktirov

Institute of Experimental Medicine

Email: ds.traktirov@gmail.com
ORCID iD: 0000-0003-0424-6545
SPIN-code: 3221-1316
Russian Federation, Saint Petersburg

Viktoriya А Maystrenko

Institute of Experimental Medicine

Email: sch_viktoriya@mail.ru
ORCID iD: 0000-0001-7004-7873
SPIN-code: 4842-2576
Russian Federation, Saint Petersburg

Gleb V. Beznin

Institute of Experimental Medicine

Email: beznin.gv@iemspb.ru
ORCID iD: 0000-0001-5730-4265
SPIN-code: 7796-1107

MD, Cand. Sci. (Medicine)

Russian Federation, Saint Petersburg

Marina N. Karpenko

Institute of Experimental Medicine

Email: mnkarpenko@mail.ru
ORCID iD: 0000-0002-1082-0059
SPIN-code: 6098-2715

Dr. Sci. (Biology), Assistant Professor

Russian Federation, Saint Petersburg

Sergey G. Tsikunov

Institute of Experimental Medicine

Email: secikunov@yandex.ru
ORCID iD: 0000-0002-7097-1940
SPIN-code: 7771-1940

MD, Dr. Sci. (Medicine), Professor

Russian Federation, Saint Petersburg

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