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Different nociceptive reactions and individual resistance were studied in rats in the initial state and in conditions of stimulation of immune processes by various methods. The aims were to study the effect of the preparation Imunofan, an immune stimulator, on various behavioral manifestations of pain reactions in animals with different individual resistances to stress and to compare the results with similar data in a natural model of immune activation. Detection of the central, immune-dependent component of the regulation of nociceptive reactions was addressed using intracerebroventricular administration of the study compound. Studies were performed on 43 male Wistar rats. Individual resistance to stress was assessed by recording the free behavior of the animals in an open field test. The following nociceptive reactions were assessed: 1) the tail withdrawal reaction using the standard tail flick method; and 2) running, twitching, jumping, and vocalization reactions to electrical stimulation of the limbs. These studies demonstrated that i.m. administration of Imunofan (10 μl of 0.005% solution) suppressed the active behavior of the animals in the open field and produced hyperalgesia, with decreases in the thresholds of nociceptive reactions. Hyperalgesia in stress-sensitive rats were significantly greater than in resistant animals. Similar results were obtained in conditions of natural activation of immunity produced by the operative intervention needed for injection of the agent into the cerebral ventricle. Intracerebroventricular administration of Imunofan was accompanied by more marked and complex changes in pain sensitivity.