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Numerous scientific studies demonstrating differences in pain sensitivity over various phases of the ovarian-menstrual cycle (OMC) in healthy women have been published in recent decades, but the basis for these differences is however still poorly understood. The aim of the current study was to assess the correlation between the heat pain threshold degree and the dynamics of TRPV1 (Transient receptor potential channeling subfamily V member1) receptor protein level, as well as aggression degree in healthy women in the follicular and luteal phases of OMC. An increased TRPV1 receptor protein level and a decreased thermal pain threshold were found in the luteal phase of the OMC. The study revealed a correlation of the progesterone level in the luteal phase with a degree of increase of TRPV1 level, as well as with the degree of decrease of heat pain threshold. The relationship between the degree of pain threshold, as well as TRPV1 level with follicle stimulating (FSH), luteinizing (LH) hormones and prolactin levels was not found. Also, there was no correlation between TRPV1 or heat pain threshold levels and aggression degree.

The application of modern techniques for different types of massage and manual therapy is associated with the exposure of the paravetrebral points. The knowledge of pain threshold values at these points is of great practical significance., Aim: The objective of the present study was to obtain the statistical characteristics of the individual pressure pain threshold (PPT) for the healthy women and patients presenting with minor disturbances of spinal motion segments (SMS) at the trigger points on the back. The secondary objective was to estimate the dependence of the PPT parameters on a variety of conditions., Material and Methods: Two groups of female volunteers (students of the South Ural State Humanitarian Pedagogical University aged 19-21 years) were formed, one composed of the girls in the quiescent state (group 1, n=45), the other comprised of the girls in the state of emotional agitation and prepared for physical activity (group 2, n=105). Each group was split into two sub-groups depending on the presence or absence of complaints about the state of the SMS. PPT was evaluated in terms of kg/cm2 with the use of the Wagner FPX algometer (USA) at 3 paired paravertebral points localized at different levels: the second and third lumbar vertebrae (LII-LIII); the ninth-to-tenth thoracic vertebrae (DIХ-DХ), the seventh cervical, and first thoracic vertebrae (CVII-DI); as well as in pairs on the trapezius muscles in their upper parts. The height, weight, and body mass index of the participants in the study were measured., Results: The PPTs values at the selected points on the back were log-normally distributed. The minimum values were measured on the trapezoidal muscles (about 2 kg/cm2) and the maximum ones in the lumbar spineregion (up to 7 kg/cm2). Complaints about the condition of SMS in group 1 were associated with the decrease of the PPT values at the paravertebral points on the neck and the lower back. No decrease of the PPT values in connection with the complaints was documented in the patients of group 2. The PPT values determined in the women of group 2 were statistically higher than in those of group 1 at all points studied and in all the subgroups; the differences ranged from 20% to 40%. The PPTs values at different points of the back correlated significantly between each other (Spearman correlation coefficient 0.6-0.9, p<0.001). In all the groups statistically significant asymmetry of the PPT values was documented (Kruskal-Wallis test, p<0.05); the right-side PPT values were lower than the left-side ones, with the difference amounting to 2-8%., Conclusion: The conditions of PPT measurements at the paravertebral points have a significant impact on the resultant values, being higher when the subject is ready for performing the physical exercises. The complaints about the state of the SMS are associated with the decrease in the PPT values that are lower on the right side of the body than on its left side.

The pain threshold effects of a neurotensin NT (8 - 13) dipeptide analog (dilept), morphine, and their combination have been studied using the tail flick test in rats. The animals of another experimental group were administered with morphine in increasing doses (10 - 20 mg/kg, i.p.) for 5 days in order to induce the state of dependence. The physical dependence on morphine was evaluated in the open-field test by monitoring 16 specific behavioral signs of withdrawal syndrome (WS) induced by the opioid receptor antagonist naloxone, after which the WS total index was calculated. It was established, that dilept (1.6 mg/kg, i.p.) produced a mild analgesic effect via increasing the pain threshold by 34% (p < 0.01), did not effect on the morphine analgesic effect, and decreased the expression of morphine WS by 29.1 and 37.5% (p < 0.01) after a single or subchronic administration, respectively. These behavioral effects of dilept were accompanied by normalization of dopamine and serotonin turnover in the hypothalamus, frontal cortex, and striatum of experimental animals.

Definition of pain in newborns with surgical pathology in the traditional way (change the child's behavior, skin color, heart rate, mean arterial pressure, body temperature, blood gas parameters) is subjective. The "Med-Storm" pain stress detector, manufactured by "Med-Storm Innovation AS" (Norway) allows the quantification of pain during and after surgery in infants. For a small sample, specificity was 76%, sensitivity--89%. Important indicator was the peak skin conductance. The change in the area under the curve was less often, but indicated the need of analgesia dose change.

Pain tolerance was assessed in 44 volunteers by the analysis of their reports during blood collection using a 12-point verbal rating scale. Thereafter, pain intensity in response to 5 successive pricks was measured with a mechanical algesimeter, and the participants of the study were asked to evaluate pain sensation based on a 0-100 score visual-analogous scale. The test was discontinued as soon as a patient reported painful feeling in excess of 50 scores. Twenty nine patients passed all the five tests while 11, 2, and 2 were able to tolerate 4, 3, and 2 challenges respectively. It was shown that the results of self-evaluation of painful sensation based on the verbal rating scale correlated with the number of tolerated test challenges. There was no significant correlation between the described signs. It is concluded that the methods for the assessment of pain tolerance described in this paper make it possible to predict the behaviour of a group as a whole but not of individual subjects.

Electrode for selective nociception specific stimulation was described by H. Kaube et al. in 2000. The aim of this work was to test this electrode in assessment of nociceptive reactions of the segmental and suprasegmental levels. The method of nociception specific blink reflex based on the use of this electrode was applied in a modified variant for examination of patients with a tension type headache. A decrease in the nociceptive reflex threshold was revealed in patients with episodic headaches (as compared to healthy volunteers). Both the reflex and pain thresholds were decreased in patients with a chronic headache. These results indicate the sensitization of nociceptive structures in patients with a headache. Cerebral evoked potentials elicited by skin stimulation of face and extremities with Kaube electrode were studied in healthy volunteers. The dominance of the late components (100-300 ms) considered to be of nociceptive origin was revealed in the pattern of evoked potentials. Thus, the electrode assures a high degree of selectivity of the pain-specific stimulation. Its adaptation for assessment of various nociceptive reactions can perfect the neurophysiological methods of nociception studies.

The paper provides quantitative assessment of acute pain during the standard blood sampling procedure. The estimates of the impact of sex and age on the level of pain sensation were determined using two different visual scales in the evaluation of pain.

The authors dwell upon the structure and functioning of the nociceptive system and modification of pain sensitivity by ambient factors like air temperature and atmospheric pressure.

The paper is dedicated to electroencephalographic monitoring in the therapy and rehabilitation of patients with acute radicular pain syndromes of the disc etiology. Spontaneous electromyograms (EMG) of the shin muscles in healthy and affected legs and stimulation electroneurograms were registered in 52 patients; the readings were subsequently processed on the basis of Fourier analysis for the 4-sec maximal muscle contraction. The studies made it possible to detect the degree of destructive changes in the neuromotor apparatus and to monitor its functional recovery in pharmacotherapy, central and peripheral blocks, artificial correction of movements and in acupuncture.

The effect of hormones of hypothalamic-pituitary-adrenocortical system on pain sensitivity were studied in experiments on awake Sprague-Dawley males rats. Pain sensitivity was tested by tail flick reaction induced by thermal stimuli. Systemic glucocorticoids and ACTH injection increased the tail flick latency. The ACTH-induced analgesic effect was unaffected by deficiency of glucocorticoids production in pretreatment with pharmacological dose of cortisol but was fully eliminated by pretreatment with opiate antagonist naltrexone. These findings suggest that ACTH-induced analgesic effect is mediated by opiate receptors but not by glucocorticoids released in response to ACTH injection.

Modern data of study of transmembrane ions currents (through the sodium-potassium- and calcium-channels) in the mechanism of pathological pain syndromes were reviewed. Tetrodotoxyn-resistant sodium currents, abnormal combinations of different types of sodium-channels during the inflammation, neuropathies (syndromes hyperalgesii and allodonii) and diabetic neuropathy analyzed. The role of pain sensitivity transmitters was demonstrated. Nerve Grow Factor plays the important role in the sodium-channels genes expression. Different types of transmembrane calcium currents participated in hyperalgesium and hypoalgesium analyzed. The summary mechanism of pain suggested as voltage-calcium-channels activation and transsynaptic NMDA receptors excitation that should be conductive the neurons hyperexcitation and force of synaptic transmission.

Various behavioural nociceptive reactions and individual resistance against stress were studied under conditions of stimulation of the immune processes by various techniques. The research problems included a study of influence of the immune stimulation with preparation "Imunofan" upon pain responses depending on individual resistance of animals to a stress, and the obtained results were compared with similar data in natural model of immune activation. To reveal central immune regulation of nociceptive reactions, imunofan was injected into brain ventricles. The work was carried out in 43 "Wistar" adult male rats. Free "open field" behaviour of animals was recorded to define a stress-resistance. Following nociceptive reactions, tail-flick to thermal stimuli; start, escape, jumping and vocalization to electrical skin stimulation, were studied. It was shown that intramuscular injection of imunofan (0.01 ml, 0.005% solution) depressed an active behaviour of animals in open field and reduced pain thresholds. This hyperalgesia was much higher in non-resistant rats in comparison to the resistant ones. Similar results were obtained in natural activation of immunity caused by operative procedure necessary for injection of imunofan into ventricles. Intracerebroventricular injections were accompanied by stronger and more complex changes of pain sensitivity.

Will the aid of a modified apparatus the authors determined the sensory thresholds of tactile, and pain sensitivity, and the limit of pain tolerance. Subject to measurement were 500 persons. By the nature of the initial high sensitivity (minor thresholds), moderate (medium) and low (major thresholds) ones. The effect of taking by mouth metherasine (0.025) and amidopyrine with analgin (0.25 each) was analyzed in each group. It was ascertained that the mechanism of their action, produced the greatest effect in persons with an initially elevated sensitivity to pain stimulators. Metherasine changed to a greater extent the pain tolerance thresholds, whereas amidopyrin with analgin did the same with the pain thresholds. In individuals with an initially elevated pain sensitivity both the pain threshold and that or the pain tolerance were higher. These date are of importance for rational approach to an individual choice of substances to be prescribed with a different attitude to pain.

The effects of a single and repetitive administration of m-cholinoblocker scopolamine (Sc) to male rats on retention of step-through passive avoidance (PA) or active avoidance (AA) in a shuttle-box were compared. In case of PA Sc (1 mg/kg) was injected i.p. only 30 min before training, only 30 min before testing, or both before training and before testing. In case of AA Sc (0.5 mg/kg/day) was injected i.p. only 15 min before each training session or both before training and before testing (44 days after achievement of learning criterion). The PA and AA retention were impaired only in the experiments, where the drug was administered before training, but did not differ from control, when Sc was injected twice. The Sc-induced amnesia (like many other cases of memory deficits) is suggested to be a manifestation of state-dependent learning. Similarity between the brain state during memory consolidation and during the retention test is necessary for recollection.

The paper deals with specific characteristics of pain sensitivity, types of anxiety disorders in patients with rheumatoid arthritis and their correlation.

Experiments on conscious rats studied the effects of systemic or central application of a nitric oxide (NO) donor or NO-synthase inhibitor on the pain sensitivity threshold. Injection of SNAP in doses of 0.2, 2.0, and 20.0 micrograms into the subarachnoidal space of the ventral medulla through a preimplanted steel cannula was accompanied by a dose-dependent change in tail-flick latency. Intraperitoneal injection of 30 mg L-NAME also increased pain sensitivity threshold levels. The findings suggest that the decrease in pain sensitivity after systemic NO-synthase inhibitor administration is due to the modulation of NO-dependent processes at both the central and peripheral levels.

Anxiety and motor activity of female white rats in the elevated plus-maze were studied at different stages of the reproduction cycle (estrus, diestrus, pregnancy and lactation). The level of anxiety was lower, and that of locomotor and exploratory activity was higher during estrus and lactation than during diestrus and pregnancy. Exposure to chronic pain of threshold intensity did not induce behavioral changes in pregnant rats. There was no difference between the control and experimental animals in the level of plasma corticosterone.

Rat experiments were made to study effects of magnetic fields varying in parameters on the course of endotoxemia and relevant changes. Dynamics of temperature and pain reactions, some biochemical indices depends much on frequency and impulse characteristics of low-frequency magnetic field.

The spectral analysis of over 50-hour series of observations (tail flick) has revealed two ultradian periodicities of rat pain sensitivity with 8- and 12-hour duration and the circadian one. The minimum sensitivity was observed in the first half of the light phase. Morphine (5 mg/kg i.p.) did not change the spectrum of rhythms, but inverted the phase of a circadian constituent--it was most effective in the middle of the dark phase. Naloxone (1 mg/kg) significantly changed the spectrum of ultradian rhythms, but did not alter the length and phase of circadian periodicity. After moradol (1 mg/kg) administration it could decrease and alter the spectrum of periodicities with the most prominent infradian rhythm. On the contrary, metamizole (50 mg/kg) injections did not interfere the rhythmic pattern of pain sensitivity. Thus, narcotic analgesics have specific effects on the chronological organization of pain sensitivity rather than non-narcotic ones do.

The dynamics of nociception was studied in young male volunteer students with different indices of extraversion and neurotism under conditions of their relative psychoemotional rests and psychoemotional tension induced by academic exams and blood-donation procedures. The averaged somatosensory potentials evoked by threshold electrodermal pain stimuli were recorded in the state of rest and during performance of computer-adapted proof-reading test. In ambivalent, sanguine, choleric, and phlegmatic persons the mean values of nociception thresholds differed between testing situations and rest. Processual motivation diminished pain perception. Characteristics of the evoked responses changed depending on the individual typological properties and motivation-determined states. The dynamics of pain subjective evaluation was different in subjects with different individual typological characteristics.

Circadian oscillations of the 8-hr rhythmic components in nociceptive sensitivity were found in mice. A 12-hr rhythm was close to a sinusoidal one. Circadian waves of the pain threshold were asymmetric and the highest in the middle of the light phase, about 16 hrs. The group rhythms of nociceptive sensitivity appeared to be a result of synchronised separate rhythms.

The circadian and ultradian rhythms of threshold pain sensitivity to different nociceptive stimuli-thermal (tail-flick) and mechanical (tail pressure)--were revealed by cosinor analysis in male rats without or after drug administration. The minimal pain sensitivity to mechanical pressure was observed during the first half of the dark phase, that to thermal stimulus during the first half of the light phase. Biorhythms of thermal pain sensitivity of mice and rats are characterized by the same parameters. Opioid receptor morphine, buprenorphine, butorphanol, morphoceptin, and U-50,488H showed individual day patterns of analgesia, which depended on the type of nociceptive stimuli. The most distinct shifts of the acrophase of circadian rhythm from the control were observed after morphine, butorphanol, and U-50,488H. A conclusion is made that drug interaction with kappa-opiate receptors contributes to the regulation of pain sensitivity biorhythms.

At least four food peptides were found to possess opiate-like and antibacterial properties, lys-arg-fen-ala-glu being the most active one. These peptides seem to be able to become accumulated in high concentrations in indigestion and induce an intestinal spasm and constipation.

The antibodies to serotonin modulate behavioural reactions of animals depending on the mode of administration (intracerebroventricular or intraperitoneal) and the testing time. Intraventricular injection induces inhibition of behavioural activity within 1--2 hours. Systemic injection produces a biphasic effect on the serotoninergic system, i. e., the activation in the early period and the steady inhibition later. Effects of the intraperitoneally injected serotonin antibodies on the CNS are probably mediated either by serotonin binding in blood or by involvement of neurotrophic factors of the immune system. Both ways of administration of the serotonin antibodies result in late hyperalgesia.

The influence of thyrotropin-releasing hormone (TRH) on morphine-induced analgesic and reinforced responses was studied in two inbred strains of rats, Fischer-344 (F344) and Wistar Albino Glaxo/GSto (WAG). Conditioned place preference, voluntary consumption of morphine solution and analgesic action of morphine in tail immersion test were studied. There were interstrain differences in pain sensitivity, i.e., F344 rats had longer latency of tail immersion and deeper analgesic effect of morphine (5 mg/kg, ip) than WAG rats. TRH (1 mg/kg, ip) produced a stronger analgesic effect in WAG rats, while F344 rats demonstrated only slight increase in pain threshold. Administration of TRH in combination with morphine significantly stronger potentiated the effect of the latter in WAG than in F344 rats. F344 rats preferred morphine in the two-bottle choice test and consumed relatively larger amount of morphine solution in the drinking paradigm than WAG rats. Morphine in the dose of 5 mg/kg (ip) induced place preference in both rat strains. Intraventricular administration of TRH (1 mcg) produced a slight effect of place preference only in F344 rats. Preceded by morphine, such injection reduced the effect of place preference. It is suggested that WAG and F344 rats have different sensitivity of brain structures to TRH. This is probably determined by genetic differences in dissociation of analgesic and reinforcing effects of morphine.

Effect of morphine and naloxone on nociceptive sensitivity were studied in 3 rat strains, with high, low, and intermediate thresholds of nervous system excitability. The highest sensitivity to morphine correlated with its dose dependence was revealed in rats with low and high thresholds of excitability. The lowest sensitivity was found in rats with intermediate thresholds of excitability. The obtained data led to the conclusion about essential contribution of genetical control of excitability in the mechanisms of functioning of the opiate system.

Non-opioid stress-induced analgesia was studied in anesthetized rats, which were treated with electroshock (0.7 mA, 15 sec on, 15 sec off, 3 min duration) delivered through fixed hind limb electrodes. Tail-flick threshold of electroshock stimulation of the tail was used as a measure of analgesia. Stress-induced analgesia was decreased by adrenalectomy. Medullectomy did not block analgesic effect of stress. These results suggest that corticosteroids, but not enkephalins of adrenal medulla, provide the analgesia induced by short-term stress.

In experiments on different species of animals respiratory stimulating effects of naloxone, TRH and its analogue RGH 2202 during respiratory rhythmogenesis disturbances, evoked by hyperventilation of lungs, bleeding and intoxication with cyanides or opiates, were investigated. The role of opiate and NMDA receptors in respiratory centre function is discussed.

The circadian relationships between blood corticosteroids and latent period of pain reaction to hot stimulation were investigated in man and rats. There were no correlation of blood corticosteroids levels and pain latent period but the latent period increased during those time of day when the corticosteroids levels were higher in total: man--morning and day, rats--evening and night.

The thresholds of pain and non-pain responses to single electric pulses whose duration was 0.1, 1, 10, 100, and 1000 msec were comparatively analysed in healthy individuals and patients suffering from endogenous affective disorders with bi- and monopolar courses during the development of a depressive phase and after its arrest. An analysis of the mean and modal values of non-pain response thresholds revealed no significant differences in patients and healthy individuals during marked depressive disorders and only after antidepressive therapy there was a tendency to increase non-pain response thresholds. During the development of depression, the thresholds of pain responses to short test signals (0.1 and 1 msec) were significantly lower in patients than in healthy subjects. After cessation of the depressive sympathology there was an increase in pain response thresholds and their approach to those in the healthy examinees, but in the intermission there was a profound rise in pain response thresholds in patients with a bipolar course.

Effects of stimulation of areas of the negative reinforcement in hypothalamus and adjacent sites on the nociceptive evoked potentials (EP), recorded in the thalamic parafascicular complex to electrical skin stimulation of the hind paw in 30-40 days old rabbits were investigated. The stimulation of areas of the negative reinforcement in the anaesthetized animals resulted in the inhibition of the EP. Points, yielding the active-defense behaviour in the behavioural experiments, inhibited the EPs in the electrophysiological tests at the smaller current level (50-80%), than points, yielding the passive-defense behaviour (80-110%). On the contrary, the recovery period of the EP's parameters after the ceasing of the stimulation was shorter, if points were connected with the active-defense but not the passive-defense behaviour. The data obtained are considered in comparison with previous findings obtained in the investigation on the rabbits of the same age under the stimulation of areas of the positive reinforcement.

Low-intensity electromagnetic field (12.6 cm, 2375 MHz, power density 1 mW/cm2) produced retrograde amnesia in the rat passive avoidance test. No effect was registered of microwave irradiation on the open field behavior and the pain sensitivity. Functional activity of the m-cholinergic receptors decreased, but their number increased in the brain cortex. It is suggested that cholinergic system plays an important role in the effects of electromagnetic field on memory processes.

It has been established that augmentation of air pressure from 0.1 to 1.1 MPa (with 0.1 MPa intervals) was accompanied in rats with the development of progressive analgesia which was measured according to the threshold of vocalization in the test of electrical stimulation of the tail. The highest analgesic response arose at 0.7-1.1 MPa. All the animals might be divided into two groups: group 1-72% of the animals with a 200% increase of the threshold, group 2--animals with such an increase by 15%. The augmentation of the pressure of heliox (79.1% of helium, 20.9% of oxygen) also caused analgesia, but not so strong. In patients pain thresholds to the mechanical nociceptive stimulation also increased by about 43-67% and 95-100% under the influence of increased air pressure of 0.4 and 0.7 MPa, respectively. In group 1 patients (67%) pain threshold increased by 50-100%, in group 2 by 15-25%. Pretreatment with naloxone (1 mg/kg), atropine (1 mg/kg), yohimbine (1 mg/kg), parachloramphetamine (5 mg/kg) and prasosin (1 mg/kg) decreased hyperbaric analgesia in rats by 41-56, 41-56, 17-19, 17-19%, respectively. The role of increased partial pressure of nitrogen in hyperbaric analgesia and possible neurochemical mechanisms of its realization are discussed.

The focused ultrasound has been used for the comparative study of skin sensitivity to pain in 51 healthy men and 64 patients with neurasthenia, natural model of the chronic psycho-emotional stress. The patients showed a distinct tendency to a decrease of the pain threshold, lowered adaptation to the repeated threshold stimulus, sensitization. With the presence of the above-mentioned factors the pain syndrome occurred relatively more often. Taking into account the fact that the focused ultrasound of rather high intensity affects, first of all, C-afferents which are not only cutaneous but visceral nociceptors as well, an assumption is made that changes in pain sensitivity in the neurasthenic patients are not limited by skin but develop also in the inner medium forming the pain syndrome.

In twenty-eight men (the mean age 49.3 +/- 3.2 years) with different clinical varieties of angina pectoris, analysis was made of the heart rate and the grade of ischemic depression of the ST segment, associated with anginous attacks seen during bicycle ergometry and other physical exercises in the course of daily cardiomonitoring. The data obtained indicate that in the same patient, the same grade of ischemic depression of ST was recorded despite varying heart rate. On the contrary, in spite of the same heart rate the grade of ischemic depression of the segment could vary. Dynamic coronary obstruction determined by the mechanisms of adrenergic vasoconstriction is the most probable cause of changeability of the threshold of angina pectoris in patients belonging to functional classes III-IV. The probability of fluctuations in the threshold of angina pectoris should be taken into consideration in deciding expert problems and in the assessment of the efficacy of antianginal therapy.

The effect of unilateral cortical spreading depression on the threshold and latency of pain vocalisation was studied in male and female Wistar rats. The effect involved a reduction of the latency both in male and female rats. However, the left inactivation latency was shorter than the right one in male rats. Thresholds were also reduced but only in male rats and for the left inactivation alone. The data obtained suggest an inter-hemisphere asymmetry in the cortical control of pain sensitivity in male Wistar rats.