Our aim was to investigate the influence of thymic polypeptides on pain sensitivity and to analyze a possible role of the opioid system in the implementation of the analgesia caused by immobilization stress. Methods: The study was performed on male Wistar rats at the Moscow state University named after M. V. Lomonosov. We studied effects of thymus peptides: thymuline (0.15 mg/kg), fraction 5 thymosin (0.25 microgram/kg) and cattle thymus extracted product (CTEP) (0.5 mg/kg) on pain sensitivity in rats using test «tail flick» without stress, with acute (3 h) and sub acute (12 h) immobilization stress. The comparison groups were animals treated with saline and spleen polypeptides. Results: It is shown that preparations of thymus increase the threshold of pain sensitivity in the intact animals. Immobilization stress duration 3 and 12 h in thymus peptides treated rats caused a less pronounced increase in pain threshold than in the control groups (immobilization stress 3 h: CTEP-р=0.025, thymuline-р=0.022, fraction 5 thymosin-р=0.033; immobilization stress 12 h: CTEP-р=0.034, thymuline-р=0.027, fraction 5 thymosin-р=0.036.). The opioid receptor blocker naloxone (1 mg/kg) did not completely block the stress-induced analgesia, indicating the presence of both opioid and non-opioid components in this state. In thymus peptides treated rats, opioid component was less pronounced than in the control groups (CTEP-р=0.031, thymuline-р=0.026, fraction 5 thymosin-р=0.029). Conclusion: Pre-activation of the opioid system by the thymus polypeptides leads to an increase in the share of non-opioid component of the stress-induced analgesia and prevents the depletion of the opioid system in immobilization stress.

The review presents data on mutual influence of nervous system and thymus, realized through the neuroendocrine-immune interactions. The presence of adrenergic and peptidergic nerves in thymus creates conditions for implementation of the effect of neuropeptides secreted by them. These neuropeptides induce activation of thymus cells receptors and influence on the main processes in thymus, including T-lymphocyte maturation, cytokine and hormones production. In turn, thymus peptides and/or cytokines, controlled by them, enter the brain and exert influence on neuronal function, which creates the basis for changes of behavior and homeostasis maintenance in response to infection. Ageing and some infectious, autoimmune, neurodegenerative and cancer diseases are accompanied by distortion of interactions between thymus and central nervous system. Mechanisms of signaling pathways, which determine these interactions, are not revealed yet, and their understanding will promote the development of effective therapeutic strategies.