Blockade of TRPA1 with HC-030031 attenuates visceral nociception by a mechanism independent of inflammatory resident cells, nitric oxide and the opioid system.

BACKGROUND: Some studies have shown a somatic nociceptive response due to the activation of transient receptor potential A1 channels (TRPA1), which is modulated by the TRPA1 antagonist HC-030031. However, a few studies report the role of TRPA1 in visceral pain. Therefore, we investigated the participation of TRPA1 in visceral nociception and the involvement of nitric oxide, the opioid system and resident cells in the modulation of these channels. METHODS: Mice were treated with vehicle or HC-030031 (18.75-300 mg/kg) before ifosfamide (400 mg/kg), 0.75% mustard oil (50 µL/colon), acetic acid 0.6% (10 mL/kg), zymosan (1 mg/cavity) or misoprostol (1 µg/cavity) injection. Visceral nociception was assessed through the electronic von Frey test or the writhing response. Ifosfamide-administered mice were euthanized for bladder analysis. The involvement of nitric oxide and the opioid system were investigated in mice injected with ifosfamide and mustard oil, respectively. The participation of resident peritoneal cells in acetic acid-, zymosan- or misoprostol-induced nociception was also evaluated. RESULTS: HC-030031 failed to protect animals against ifosfamide-induced bladder injury (p > 0.05). However, a marked antinociceptive effect against ifosfamide, mustard oil, acetic acid, zymosan and misoprostol was observed (p < 0.05). Neither L-arginine (600 mg/kg) nor naloxone (2 mg/kg) could reverse the antinociceptive effect of HC-030031. The reduction of the peritoneal cell population inhibited the acetic acid and zymosan-related writhes without interfering with the misoprostol effect. CONCLUSIONS: Our findings suggest that the blockade of TRPA1 attenuates visceral nociception by a mechanism independent of the modulation of resident cells, nitric oxide and opioid pathways.

The placebo effect: how the subconscious fits in.

The placebo effect is very well known, being replicated in many scientific studies. At the same time, its exact mechanisms still remain unknown. Quite a few hypothetical explanations for the placebo effect have been suggested, including faith, belief, hope, classical conditioning, conscious/subconscious expectation, endorphins, and the meaning response. This article argues that all these explanations may boil down to autosuggestion, in the sense of "communication with the subconscious." An important implication of this is that the placebo effect can in principle be used effectively without the placebo itself, through a direct use of autosuggestion. The benefits of such a strategy are clear: fewer side effects from medications, huge cost savings, no deception of patients, relief of burden on the physician's time, and healing in domains where medication or other therapies are problematic.

Effectiveness of electroacupuncture analgesia compared with opioid administration in a dog model: a pilot study.

BACKGROUND: Although opioid analgesics are the usual drugs to treat post-surgical pain, acupuncture has also been demonstrated to relieve various pain syndromes. The present pilot study aims to investigate the efficacy of electroacupuncture compared with a conventional opioid compound, butorphanol, for postoperative pain treatment in dogs undergoing elective ovariohysterectomy. METHODS: Twelve dogs were randomly allocated into two groups. Dogs received either electroacupuncture stimulation (16 and 43 Hz) at Shen Shu, Chang Shu, He Gu, Tai Yuan, Zu San Li, Yang Ling Quan, and Bai Hui acupoints, while control dogs were treated with butorphanol. Cardiovascular and respiratory parameters were recorded for both groups during operation. Plasma ß-endorphin concentrations were evaluated before surgery (baseline) and up to 24 h later. For each dog, pain was measured according to a dedicated subjective pain scoring system. RESULTS: Plasma ß-endorphin levels in dogs receiving electroacupuncture increased significantly against baseline values after 1 and 3 h after surgery. Moreover, the end-tidal isoflurane concentration needed for second ovary traction was significantly lower in acupuncture-treated dogs than control animals. All animals having electroacupuncture experienced prolonged analgesia, over 24 h at least, while four out of six dogs treated with butorphanol needed post-surgical ketorolac and tramadol supplementation to their pain relief. CONCLUSIONS: The results obtained from the present investigation showed some evidence for electroacupuncture as an alternative technique to provide postoperative analgesia in dogs.

Acupuncture-related techniques for the treatment of opiate addiction: a case of translational medicine.

Drug addiction is a chronic brain disorder characterized by withdrawal symptoms that occur during drug abstinence and a high tendency of relapse. Compared with the currently available pharmacological interventions, acupuncture therapy has the potential to help drug addicts stay away from drugs without major adverse side effects. It has taken decades of research to optimize the parameters of electrical acupoint stimulation for detoxification and for relapse prevention, as well as to establish a safe and easy procedure by which drug addicts can use it on themselves. The discovery that acupuncture can trigger the release of opioid substances from the brain in the 1970s provided the inspiration. Following this, basic research on animals made it possible to understand the mechanisms of action and establish the procedure for treating drug addictions. This article reviews the past, present, and foreseeable future regarding the use of acupuncture-related technique for the treatment of opiate addiction from the perspective of translational medicine.

Neuroendocrine regulation of GnRH release and expression of GnRH and GnRH receptor genes in the hypothalamus-pituitary unit in different physiological states.

This review is focused on the relationship between neuroendocrine regulation of GnRH/LH secretion and the expression of GnRH and GnRH receptor (GnRHR) genes in the hypothalamic-pituitary unit during different physiological states of animals and under stress. Moreover, the involvement of hypothalamic GABA-ergic, Beta-endorphinergic, CRH-ergic, noradrenergic, dopaminergic and GnRH-ergic systems in the regulation of expression of the GnRH and GnRHR genes as well as secretion of GnRH/LH is analyzed. It appears that the neural mechanisms controlling GnRH gene expression in different physiological states may be distinct from those regulating GnRH/LH release. The hypothalamic GnRHR gene is probably located in different neural systems and may act in a specific way on GnRH gene expression and GnRH release.

Deal in the womb: fetal opiates, parent-offspring conflict, and the future of midwifery.

This paper argues that parent-offspring conflict is mediated by placental beta-endorphins in placental mammals, i.e., foetuses make their mothers endorphin-dependent then manipulate them to increase nutrient allocation to the placenta. This hypothesis predicts that: (1) anatomic position of endorphin production should mirror its presumed role in fetal-maternal conflict; (2) endorphin levels should co-vary positively with nutrient carrying capacity of maternal blood system; (3) postpartum psychological symptoms (postpartum blues, depression and psychosis) in humans are side-effects of this mechanism that can be interpreted as endorphin-deprivation symptoms; (4) shortly after parturition, placentophagia could play an adaptive role in decreasing the negative side-effects of fetal manipulation; (5) later, breast-feeding induced endorphin excretion of the maternal pituitary saves mother from further deprivation symptoms. Finally, whatever the molecular mechanism of fetal manipulation is, widespread and intense medical care (such as caesarean section and use of antidepressants) affects the present and future evolution of mother-foetus conflict in the human species (and also in domestic animals) to increase 'fetal aggressiveness' and thus technology-dependency of reproduction.

Antinociceptive properties of the ethanolic extract and of the triterpene 3beta,6beta,16beta-trihidroxilup-20(29)-ene obtained from the flowers of Combretum leprosum in mice.

The present study examined the antinociceptive effects of the ethanolic extract (EE) and of the triterpene 3beta,6beta,16beta-trihidroxilup-20(29)-ene obtained from the flowers of Combretum leprosum in chemical and thermal behavioural models of pain in mice. The EE (10-1000 mg/kg) given orally (p.o.), 1 h prior to testing, produced dose-dependent inhibition of acetic acid-induced visceral pain, with mean ID50 value of 131.9 mg/kg. In the formalin test, the EE (10-300 mg/kg, p.o.) also caused significant inhibition of both the early (neurogenic pain) and the late (inflammatory pain) phases of formalin-induced licking, however, it was more potent and efficacious in relation to the late phase of the formalin test, with mean ID50 values for the neurogenic and the inflammatory phases of approximately 300 and 88.8 mg/kg, respectively. The EE (10-1000 mg/kg, p.o.) also caused significant and dose-dependent inhibition of capsaicin- and glutamate-induced pain, with mean ID50 values of 160.5 and 38.3 mg/kg, respectively. Furthermore, the triterpene 3beta,6beta,16beta-trihidroxilup-20(29)-ene (1-30 mg/kg), given p.o., 1 h prior to testing, also produced dose-related inhibition of glutamate-induced pain, with a mean ID50 value of 5.6 mg/kg. When assessed in a thermal model of pain, the EE (10-300 mg/kg, p.o.) and fentanyl (100 microg/kg, s.c.) caused a significant and marked increase in the latency response on the hot-plate test (50 degrees C). The antinociception caused by EE (100 mg/kg, p.o.) in the glutamate test was significantly attenuated by intraperitoneal (i.p.) treatment of mice with naloxone (opioid receptor antagonist, 1 mg/kg), pindolol (a 5-HT 1A/1B receptor/beta adrenoceptor antagonist, 1 mg/kg), WAY100635 (a 5-HT 1A receptor antagonist, 0.7 mg/kg) or ketanserin (a 5-HT 2A receptor antagonist, 0.3 mg/kg). In contrast, EE (100 mg/kg, p.o.) antinociception was affected neither by L-arginine (precursor of nitric oxide, 600 mg/kg) nor by ondansetron (a 5-HT3 receptor antagonist, 0.5 mg/kg) i.p. treatment. It was not associated with non-specific effects such as muscle relaxation or sedation. Together, these results indicate that EE produces dose-related antinociception in several models of chemical and thermal pain through mechanisms that involve an interaction with opioid and serotonergic (i.e., through 5-HT 1A/1B and 5-HT 2A receptors) systems.

Activation of spinal anti-analgesic system following electroacupuncture stimulation in rats.

We evaluated the interaction between electroacupuncture (EA)-induced antinociception and an endogenous anti-analgesic system. EA was applied to the ST-36 acupoint for 45 min in male Sprague-Dawley rats, and pain thresholds were assessed by the hind-paw pressure test. EA produced a marked increase in pain thresholds and its antinociceptive action was completely reversed by naloxone (5 mg/kg). The analgesic effects of subcutaneous morphine (7 mg/kg) following EA stimulation were significantly attenuated. The attenuation of morphine analgesia was inversely proportional to the time intervals between EA termination and morphine injection, and the effect was not observed 120 min after EA stimulation. The analgesic effects of i.t. morphine (10 microg), but not i.c.v. morphine (25 microg), following EA were also attenuated. On the other hand, systemic morphine (7 mg/kg)-induced hyperthermia was not affected by EA. Moreover, i.c.v. morphine, but not i.t. morphine, produced hyperthermia. The i.c.v. morphine-induced hyperthermia was not affected by EA, similar to i.c.v. morphine analgesia. These results suggest that the attenuation of morphine analgesia following EA, that is, the activation of an endogenous anti-analgesic system, is closely related to the activation of an analgesic system by EA and that the spinal cord plays a critical role in the activation of the endogenous anti-analgesic systems.

Corticostriatal-hypothalamic circuitry and food motivation: integration of energy, action and reward.

Work over the past decade has supported the idea that discrete aspects of appetitive motivation are differentially mediated by separate but interacting neurochemical systems within the nucleus accumbens (Acb). We review herein a series of studies in rats comparing the effects of manipulating Acb amino acid, opioid, acetylcholine, and dopamine systems on tests of free-feeding and food-reinforced operant responding. Results from our laboratory and in the literature support three general conclusions: (1) GABA output neurons localized exclusively within the Acb shell directly influence hypothalamic effector mechanisms for feeding motor patterns, but do not participate in the execution of more complex food-seeking strategies; (2) enkephalinergic neurons distributed throughout the Acb and caudate-putamen mediate the hedonic impact of palatable (high sugar/fat) foods, and these neurons are under modulatory control by striatal cholinergic interneurons; and (3) dopamine transmission in the Acb governs general motoric and arousal processes related to response selection and invigoration, as well as motor learning-related plasticity. These dissociations may reflect the manner in which these neurochemical systems differentially access pallido-thalamo-cortical loops reaching the voluntary motor system (in the case of opioids and dopamine), versus more restricted efferent connections to hypothalamic motor/autonomic control columns (in the case of Acb shell GABA and glutamate systems). Moreover, we hypothesize that while these systems work in tandem to coordinate the anticipatory and consummatory phases of feeding with hypothalamic energy-sensing substrates, the striatal opioid network evolved a specialized capacity to promote overeating of energy-dense foods beyond acute homeostatic needs, to ensure an energy reserve for potential future famine.

Behavioral alterations in rats prenatally exposed to valproic acid: animal model of autism.

Autism is a severe behavioral disorder characterized by pervasive impairments in social interactions, deficits in verbal and nonverbal communication, and stereotyped, repetitive patterns of behaviors and interests. Recently, a new rodent model of autism was created by exposure of rat fetuses to valproic acid (VPA) on the 12.5th day of gestation (VPA rats). The model has striking anatomical, pathological, and etiological similarities to human data; however, it has not been characterized behaviorally. In order to determine if VPA rats present behavioral aberrations observed in autism, their behavior was extensively evaluated in a battery of tests. The results of the present experiments demonstrate that VPA rats exhibit: (1) lower sensitivity to pain and higher sensitivity to nonpainful stimuli, (2) diminished acoustic prepulse inhibition, (3) locomotor and repetitive/stereotypic-like hyperactivity combined with lower exploratory activity, and (4) decreased number of social behaviors and increased latency to social behaviors. In addition, VPA rats showed delayed maturation, lower body weight, delayed motor development, and attenuated integration of a coordinated series of reflexes, delayed nest-seeking response mediated by olfactory system, and normal negative geotaxis. Interestingly, all behavioral aberrations described in this paper appear before puberty, which could distinguish the VPA rat model of autism from other animal models of neurodevelopmental disorders, especially rodent models of schizophrenia. Our results bring further support to validity of the proposed VPA animal model of autism, suggesting similarities between the observed pattern of behavioral alterations in VPA rats and features of disturbed behavior in autistic patients.

The role of endogenous opioids in the placebo effect in post-traumatic stress disorder.

The concept of the placebo effect has received a considerable attention over the past several decades. The placebo effect has been observed in different psychiatric disorders, including post-traumatic stress disorder (PTSD), a chronic and severe disorder precipitated by exposure to a psychologically distressing event. The placebo response rates in patients with PTSD range from 19% to 62%. A considerable number of research publications suggest that endogenous opioids are involved in the mechanisms of the placebo effect. Endogenous opioid peptides play an important role in stress response and in the pathophysiology of PTSD. Therefore, endogenous opioids may be involved in the neurobiology of the placebo effect in PTSD. Possibly, the endogenous opioid system mediates the effect of placebo on all 3 PTSD symptom clusters (re-experiencing symptoms, avoidance and numbing, and physiologic arousal). The placebo effect-related activation of the endogenous opioid system may result in an improvement in intrusive symptomatology and symptoms of increased arousal because the administration of exogenous opioids improve these symptoms. The placebo effect-related activation of the endogenous opioid system may have a mood-enhancing effect, and, consequently, diminish avoidance and numbing. Multiple neurotransmitter and neuroendocrine pathways may be involved in the mechanisms of the placebo effect in PTSD. Further studies of the neurobiology of the placebo effect on patients with PTSD and other psychiatric disorders may produce interesting and important results.

Pentacyclic triterpenoids, alpha,beta-amyrins, suppress the scratching behavior in a mouse model of pruritus.

In the search for natural compounds useful against pruritus, alpha,beta-amyrins, the pentacyclic triterpenes isolated from the resin of popular medicinal plant Protium heptaphyllum were examined on scratching behavior induced by dextran T40 and compound 48/80 in mice. The animals were pretreated orally with alpha,beta-amyrins (50, 100 and 200 mg/kg) or cyproheptadine (10 mg/kg), an antagonist of histamine and serotonin receptors and 2 h later, they were given subcutaneous injections of dextran T40 (75 mg/kg) or compound 48/80 (3 mg/kg) into the rostral back, and scratching was quantified for 20 min. The scratching behavior induced by dextran T40 and compound 48/80 was significantly inhibited in mice pretreated with alpha,beta-amyrins (100 and 200 mg/kg) or cyproheptadine (10 mg/kg), In addition, the compound 48/80-elicited degranulation of rat peritoneal mast cells (ex vivo) was also markedly reduced in animals pretreated with alpha,beta-amyrins (100 mg/kg) or ketotifen (1 mg/kg), a known mast cell stabilizer. In the open-field test, alpha,beta-amyrins (100 and 200 mg/kg)-pretreated mice showed no impairment of spontaneous locomotion, suggesting that these triterpenoids possess no sedative activity that could account for suppression of scratching behavior. These results clearly indicate the antipruritic effect of alpha,beta-amyrins and suggest that this effect may be related to a stabilizing action on mast cell membrane.

Selectins and integrins but not platelet-endothelial cell adhesion molecule-1 regulate opioid inhibition of inflammatory pain.

1. Control of inflammatory pain can result from activation of opioid receptors on peripheral sensory nerves by opioid peptides secreted from leukocytes in response to stress (e.g. experimental swim stress or surgery). The extravasation of immunocytes to injured tissues involves rolling, adhesion and transmigration through the vessel wall, orchestrated by various adhesion molecules. 2. Here we evaluate the relative contribution of selectins, integrins alpha(4) and beta(2), and platelet-endothelial cell adhesion molecule-1 (PECAM-1) to the opioid-mediated inhibition of inflammatory pain. 3. We use flow cytometry, double immunofluorescence and nociceptive (paw pressure) testing in rats with unilateral hind paw inflammation induced by complete Freund's adjuvant. 4. In inflamed tissue, 43-58% of hematopoietic cells (CD45(+)) expressed opioid peptides. L-selectin and beta(2) were coexpressed by 7 and 98% of opioid-containing leukocytes, respectively. Alpha(4) integrin was expressed in low levels by the majority of leukocytes. Opioid-containing cells, vascular P- and E-selectin and PECAM-1 were simultaneously upregulated. 5. Swim stress produced potent opioid-mediated antinociception in inflamed tissue, unaffected by blockade of PECAM-1. However, blockade of L- and P-selectins by fucoidin, or of alpha(4) and beta(2) by monoclonal antibodies completely abolished peripheral stress-induced antinociception. This coincided with a 40% decrease in the migration of opioid-containing leukocytes to inflamed tissue. 6. These findings establish selectins and integrins alpha(4) and beta(2), but not PECAM-1, as important molecules involved in stress-induced opioid-mediated antinociception in inflammation. They point to a cautious use of anti-inflammatory treatments applying anti-selectin, anti-alpha(4) and anti-beta(2) strategies because they may impair intrinsic pain inhibition.

[Neurophenomenological analysis of the therapeutic relationship in ritual healing]. / A terápiás kapcsolat neurofenomenológiai elemzése a rituális gyógyításban.

In this essay we examine some phenomena of community rituals, especially healing ceremonials, which are considered neurobiologically mediated, complex forms of attachment. Recent studies in medical anthropology have pointed out that the ritual therapeutic experience relies on the patients' own healing processes by means of various altered states of consciousness that healers are able to control. Ritual trance invariably occurs in social context, and the healer's personality and the expectations of the community are profoundly involved in the induction of altered states of consciousness. Trance state is regarded as a result of the mobilisation of endogenous opiates, as an activation of the organism's defensive mechanisms in face of the stress of ceremonial. On the other hand, there is a growing body of evidence that opiate mechanisms are involved in social behaviour as well, especially in symbiotic bonds. It is suggested that this is the neurobiological reason why attachment facilitates trance induction. The homeostatic role of social relationships as physiological regulators is also discussed.

Mechanisms of pain-induced local cerebral blood flow changes in the rat sensory cortex and thalamus.

It is a well-known phenomenon that cerebral blood flow is coupled to neural activation induced by non-noxious somatosensory stimulation. However, basic questions related to pain-induced cerebral blood flow changes remain unanswered. In the present study, the sciatic nerve of anesthetized rats was subjected to electric stimulation with noxious and non-noxious parameters. Changes in local cerebral blood flow and neuronal activity were determined simultaneously in the sensory cortex and in the thalamus by laser-Doppler flowmetry and c-fos immunohistochemistry, respectively. The role of different vasoregulatory mechanisms and the pain-induced increase in mean arterial blood pressure (MABP) were examined with specific blocking agents and by means of rapid intra-arterial transfusion. Noxious stimulation resulted in significant enhancement of neuronal activity both in the thalamus and in the somatosensory cortex indicated by marked c-fos expression in these areas. Cortical and thalamic blood flow (cBF and tBF) increased by 47+/-4 and 44+/-3% during the stimulation while the MABP elevated by 35+/-2%. Similar changes in MABP induced by intra-arterial transfusion had no effect on tBF, while cBF increased only by 18+/-5%. Blockade of ATP sensitive potassium channels (K(+)(ATP)) and sympathetic beta-receptors significantly attenuated the pain-induced blood flow increases in both investigated areas, while inhibition of nitric oxide synthase was effective only in the thalamus. The blockade of the sympathetic alpha-receptors, opiate receptors, and the cyclooxygenase enzyme had no effect on the pain-induced cerebral blood flow elevations. These findings demonstrate that during noxious stimulation, cerebral blood flow is adjusted to the increased neural activity by the interaction of vasoconstrictor autoregulatory and specific vasodilator mechanisms, involving the activation of sympathetic beta-receptors, K(+)(ATP)-channels and the release of nitric oxide.

Characteristics of electroacupuncture-induced analgesia in mice: variation with strain, frequency, intensity and opioid involvement.

The present study was conducted to evaluate the characteristics of electroacupuncture (EA)-induced analgesia in mice. Three inbred strains of mice (DBA/2, C57BL/6J, BALB/c) and three outbred strains (ICR, LACA, NIH) were used in the experiment. Two pairs of metallic needles were inserted into acupoints ST 36 and SP 6 connected to an electric pulse generator. EA parameters were set as constant current output with alteration of a positive and negative square wave, 0.6 ms in pulse width for 2 Hz and 0.3 ms for 100 Hz. Tail-flick latencies evoked by radiant heat were measured before, during and after EA stimulation. We found that (1) DBA/2 mice showed a significantly more potent analgesic effect than the other five strains in response to both 100 and 2 Hz EA. In this case, the intensities were 1.0-2.0-2.0 mA, 10 min for each intensity totally 30 min. (2) EA analgesia increased as the intensity of stimulation increased from 0.5 to 2.0 mA, but it remained at this plateau when the intensity further increased from 2.0 to 3.0 mA. (3) 10.0 mg x kg(-1) naloxone was needed to block the analgesic effect induced by 2 Hz EA of 2.0 mA, but to block that by 100 Hz, 25.0 mg x kg(-1) was necessary. (4) A positive correlation was observed between analgesia induced by morphine at the dose of 5.0 mg x kg(-1) and by 100 Hz EA in two tested strains DBA/2 and C57BL/6J. In conclusion, EA induces reliable, strain-dependent analgesia in mice. The naloxone-reversibility of EA, a measure of whether it is opioid or non-opioid mediated, is dependent upon intensity and frequency.

Acupuncture beyond the endorphin concept?

Traditional acupuncture has been used for treating a variety of health conditions. In contrast, Western physicians limited acupuncture to the alleviation of pain. Concomitant with a recent view that not all kinds of pain are within the reach of acupuncture-induced relief, it has been suggested that some conditions other than pain can be effectively treated by this method. Increased release of the neuropeptide beta-endorphin was proposed to explain the antinociceptive function of acupuncture. Even if correct beta-endorphin cannot account for the effect of acupuncture in other conditions. Endorphins might be interacting with cytokines, some of which (e.g. interleukin-10) downregulate the inflammatory component of disorders in which acupuncture may be useful. We present a speculative notion of the view that acupuncture may amplify the interaction between neuropeptides and cytokines. A non-invasive approach, such as immune-committed cells harvested from blood of acupuncture-treated patients, could be used to examine this hypothesis. Inclusion of a placebo group might support the credibility of acupuncture.

Devices for noninvasive transcranial electrostimulation of the brain endorphinergic system: application for improvement of human psycho-physiological status.

It is well known that deficit of endorphins plays an important role in disturbances of human psycho-physiological status. Previously, we revealed that brain endorphinergic structures have quasiresonance characteristics. On the basis of these data, a method of activation of the brain endorphinergic structures by means of noninvasive and rather selective transcranial electrostimulation (TES) as a kind of functional electrical stimulation (FES) was elaborated. New models of TES devices (TRANSAIR) were developed for indoor and outdoor usage. To increase the efficacy of TES, the frequency modulation according to normal distribution in the limits of the quasiresonance characteristics was put into operation. The blind and placebo-controlled (passive and active placebo) study was produced to estimate the TES effects on stress events and accompanied psycho-physiological and autonomic disturbances of different intensities on volunteers and patients in the following groups: everyday stress and fatigue; stress in regular military service and in field conditions; stress in the relatives of those lost in mass disaster; posttraumatic stress (thermal burns); and affective disorders in a postabstinence period. Some subjective verbal and nonverbal tests and objective tests (including heart rate variability) were used for estimation of the initial level of psycho-physiological status, which changes after TES sessions. It was demonstrated that fatigue, stress, and other accompanied psycho-physiological disturbances were significantly improved or abolished after 2-5 TES sessions. The TES effects were more pronounced in cases of heavier disturbances. In conclusion, activation of the brain endorphinergic structures by TES is an effective homeostatic method of FES that sufficiently improves quality of life.

[Noninvasive transcranial electrostimulation of endorphin structures of the brain as a reparation activator: experimental and clinical parallels]. / Neinvazivnaia transkranial'naia élektrostimuliatsiia éndorfinnykh struktur mozga kak aktivator reparatsii: éksperimental'no-klinicheskie paralleli.

The authors evaluated the capacities of transcranial electrostimulation and the specific features of its impact on reparative regeneration of damaged tissues of different types, such as the dermal and gastroduodenal epithelium, hepatic cells, connective tissue, peripheral nerve fibers, on animal experimental pathological models and compared with the results of treatment of respective pathology in patients.

Effects of aging on the opioid modulation of feeding in humans.

OBJECTIVES: To determine whether aging is associated with a reduction in the opioid modulation of feeding, which may be important in the pathogenesis of the "anorexia of aging." DESIGN: Three studies on separate days, in randomized order and double-blind fashion. SETTING: Clinical Human Research Laboratory, Department of Medicine, RAH, Adelaide, Australia. PARTICIPANTS: Twelve older (5 male/7 female) (age 65-84) and 12 young (5 male/7 female) (age 20-26) healthy subjects. INTERVENTION: Subjects received in double-blinded random order, intravenous bolus (10 minutes) and then continuous (140 minutes) infusions of saline (control), naloxone low dose (LD) (bolus 27 microg/kg; continuous 50 microg/kg/hr), or naloxone high dose (HD) (bolus 54.5 microg/kg; continuous 100 microg/kg/hr). MEASUREMENTS: After 120 minutes, subjects were offered a buffet meal, and their energy intake was quantified. Hunger, fullness, nausea, and drowsiness were assessed using visual analogue scales. RESULTS: The naloxone LD and HD infusions had no significant effect on ratings of hunger, fullness, or nausea, but increased drowsiness (P < .01) compared with the control infusion in both age groups. Older subjects ate less (P < .001) at the buffet meal than young subjects during all three infusions. Naloxone infusions reduced energy intake compared with control (P < .001), LD by 13.2 +/- 5.0% and HD by 10.7 +/- 5.0%, with no difference between the doses (P = .71). Overall, naloxone suppressed energy intake in both young and older subjects (P < .01). This suppression was slightly, but not significantly, greater in young than in older subjects (mean of LD and HD 16.4 +/- 4.9% vs 7.5 +/- 4.9%, P = .42), because of a trend to reduced suppression in older women. CONCLUSIONS: We conclude that healthy older adults retain their sensitivity to the suppressive effects of naloxone on food intake. Possible gender differences in this sensitivity warrant further investigation. A decline in opioid activity is unlikely to contribute substantially to the physiological anorexia of aging observed in older people.