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Effect of melatonin on the nociceptive sensitivity of rats during antigenic stimulation with lipopolysaccharide

Keywords:

A. Yu. Kozlov – Ph.D. (Biol.), Senior Research Scientist, P.K. Anokhin Institute of Normal Physiology (Moscow). E-mail: brama59@mail.ru
A. Yu. Abramova – Ph.D. (Мed.), Senior Research Scientist, P.K. Anokhin Institute of Normal Physiology (Moscow). E-mail: nansy71@mail.ru
A. S. Pertsov – Student, I.M. Sechenov First Moscow State Medical University (Moscow). E-mail: s.pertsov@mail.ru


The impairment of neuroimmune interactions serves as a general mechanism for the pathogenesis of pain syndromes of unknown etiology. Much attention is paid to the search for endogenous biologically active compounds with immunomodulatory properties, which can prevent pathological changes in pain sensitivity of mammals. The epiphyseal neurohormone melatonin is one of these substances. This work was designed to study the effect of melatonin on the perceptual and emotional components of nociceptive sensitivity in rats receiving a natural immune-stimulating agent, lipopolysaccharide (LPS). Experiments were performed on 46 male Wistar rats. The animals were divided into the following groups: (I) i.p. injection of LPS in a dose of 30 µg/kg; (II) i.p. injection of melatonin in a dose of 10 mg/kg; (III) i.p. injection of melatonin 40 min prior to LPS treatment; and (IV) i.p. injection of saline (control). The nociceptive thresholds in rats were measured under basal conditions and 12 h after administration of study substances. The perceptual component of nociception in animals was evaluated from the tail-flick latency in response to light-and-thermal stimulation of the tail (sec). The emotional component of nociception in rats was determined from the vocalization threshold during electrocutaneous stimulation of the tail (0.25…1 mA). Antigenic stimulation with LPS was accompanied by a significant increase in the perceptual component, but decrease in the emotional component of nociception in rats. Variations of nociceptive sensitivity in rats receiving an intraperitoneal injection of melatonin were opposite to those induced by LPS. Administration of melatonin induced a statistically significant decrease in the perceptual component, but increase in the emotional component of nociception in rats. Our experiments revealed that an intraperitoneal injection of melatonin 40 min prior to LPS treatment had no effect on the directionality, but reduced the severity of nociceptive changes induced by antigenic stimulation. Variations in the nociceptive thresholds of animals were not statistically significant under these conditions. Our results indicate that melatonin reduces the degree of nociceptive variations in animals upon an LPS-induced change in the immune status. These data form a basis to develop indications for the clinical use of melatonin in patients with pain syndromes of different etiology.
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