Role of cholinergic, opioidergic and GABAergic neurotransmission of the dorsal hippocampus in the modulation of nociception in guinea pigs

Aims: Several physiological, pharmacological and behavioral lines of evidence suggest that the hippocampal formation is involved in nociception. The hippocampus is also believed to play an important role in the affective and motivational components of pain perception. Thus, Our aim was to investigate the participation of cholinergic, opioidergic and GABAergic systems of the dorsal hippocampus (DH) in the modulation of nociception in guinea pigs. Main methods: The test used consisted of the application of a peripheral noxious stimulus (electric shock) that provokes the emission of a vocalization response by the animal. Key findings: Our results showed that, in guinea pigs, microinjection of carbachol, morphine and bicuculline into the DH Promoted anti nociception, while muscimol promoted pronociception. These results were verified by a decrease and all increase, respectively, in the vocalization index in the vocalization test. This antinociceptive effect of carbachol (2.7 nmol) was blocked by previous administration of atropine (0.7 nmol) or naloxone (1.3 nmol) into the same site. In addition, the decrease in the vocalization index induced by the microinjection of morphine (2.2 nmol) into the DH was prevented by pretreatment with naloxone (1.3 nmol) or muscimol (0.5 nmol). At doses of 1.0 nmol, muscimol microinjection caused pronociception, while bicuculline promoted antinociception. Significance: These results indicate the involvement of the cholinergic, opioidergic and GABAergic systems of the DH in the modulation of antinociception in guinea pigs. In addition, the present study suggests that cholinergic transmission may activate the release of endorphins/enkephalin from interneurons of the DH, Which Would inhibit GABAergic neurons, resulting in antinociception. (C) 2008 Elsevier Inc. All rights reserved.

Endogenous opioid peptides in parasympathetic, sympathetic and sensory nerves in the guinea-pig heart.

Research has suggested that exogenous opioid substances can have direct effects on cardiac muscle or influence neurotransmitter release via presynaptic modulation of neuronal inputs to the heart. In the present study, multiple-labelling immunohistochemistry was employed to determine the distribution of endogenous opioid peptides within the guinea-pig heart. Approximately 40% of cardiac ganglion cells contained immunoreactivity for dynorphin A (1-8), dynorphin A (1-17) and dynorphin B whilst 20% displayed leu-enkephalin immunoreactivity. Different populations of opioid-containing ganglion cells were identified according to the co-existence of opioid immunoreactivity with immunoreactivity for somatostatin and neuropeptide Y. Immunoreactivity for prodynorphin-derived peptides was observed in many sympathetic axons in the heart and was also observed, though to a lesser extent, in sensory axons. Leu-enkephalin immunoreactivity was observed in occasional sympathetic and sensory axons. No immunoreactivity was observed for met-enkephalin-arg-gly-leu or for beta-endorphin. These results demonstrate that prodynorphin-derived peptides are present in parasympathetic, sympathetic and sensory nerves within the heart, but suggest that only the prodynorphin gene is expressed in guinea-pig cardiac nerves. This study has shown that endogenous opioid peptides are well placed to regulate cardiac function via both autonomic and sensory pathways.

Nicotine-induced release of vasopressin in the conscious rat: role of opioid peptides and hemodynamic effects.

Nicotine has been shown to stimulate the release of vasopressin and to cause significant hemodynamic changes. The mechanisms leading to enhanced vasopressin secretion and the vascular consequences of the high plasma vasopressin levels during nicotine infusion have not yet been determined. Therefore, the purposes of the present study were 1) to examine in normal conscious rats the role of opioid peptides in the nicotine-induced increase in plasma vasopressin levels and 2) to assess the role of vasopressin in the hemodynamic effects of nicotine (20 micrograms/min for 15 min) using a specific V1 antagonist of the vascular actions of vasopressin. Plasma vasopressin levels were significantly increased in the nicotine-treated animals (39.5 +/- 10 vs. 3.7 +/- 0.6 pg/ml in the controls, P less than .01). Pretreatment with naloxone, an antagonist of opioids at their receptors, did not reduce the vasopressin levels (47.7 +/- 9 pg/ml). Nicotine also increased mean blood pressure (122.5 +/- 2.5 to 145.2 +/- 3.3 mm Hg, P less than .01) and decreased heart rate (461 +/- 6 to 386 +/- 14.5 beats/min, P less than .05). Administration of the vasopressin V1 antagonist before the nicotine infusion did not affect the systemic hemodynamics or the regional blood flow distribution, as assessed by radiolabeled microspheres. Thus, these results suggest that the nicotine-induced secretion of vasopressin is not mediated by opioid receptors and that the high plasma vasopressin levels do not exert any significant hemodynamic effect on cardiac output or blood flow distribution.

Cholinergic-opioidergic interaction in the central amygdala induces antinociception in the guinea pig

Several studies have demonstrated the involvement of the central nucleus of the amygdala (CEA) in the modulation of defensive behavior and in antinociceptive regulation. In a previous study, we demonstrated the existence of a cholinergic-opioidergic interaction in the CEA, modulating the defensive response of tonic immobility in guinea pigs. In the present study, we investigated a similar interaction in the CEA, but now involved in the regulation of the nociceptive response. Microinjection of carbachol (2.7 nmol) and morphine (2.2 nmol) into the CEA promoted antinociception up to 45 min after microinjection in guinea pigs as determined by a decrease in the vocalization index in the vocalization test. This test consists of the application of a peripheral noxious stimulus (electric shock into the subcutaneous region of the thigh) that provokes the emission of a vocalization response by the animal. Furthermore, the present results demonstrated that the antinociceptive effect of carbachol (2.7 nmol; N = 10) was blocked by previous administration of atropine (0.7 nmol; N = 7) or naloxone (1.3 nmol; N = 7) into the same site. In addition, the decrease in the vocalization index induced by the microinjection of morphine (2.2 nmol; N = 9) into the CEA was prevented by pretreatment with naloxone (1.3 nmol; N = 11). All sites of injection were confirmed by histology. These results indicate the involvement of the cholinergic and opioidergic systems of the CEA in the modulation of antinociception in guinea pigs. In addition, the present study suggests that cholinergic transmission may activate the release of endorphins/enkephalins from interneurons of the CEA, resulting in antinociception.

The effect of synchronized group activities on pain threshold as a predictor of cooperation

Recent research suggests that participating in vigorous synchronized physical activity may result in elevated levels of endorphins, which may in turn affect social bonding (Cohen et. al., 2009). The present research aimed to examine whether or not the change in pain tolerance would be able to predict participants’ willingness to cooperate after statistically controlling for the groups’ condition. Participants were asked to run on a treadmill for 30 minutes under one of two conditions (control vs. synchronized). Prior to and after the run participants underwent a pain tolerance test. Once completed, a second activity was introduced to the participants; a cooperative game. A public goods game was used to measure an individual’s willingness to cooperate. The results showed the synchronized condition was able to predict that participants cooperated more during the public goods game (p = .009), however the change in pain threshold was unable to significantly predict cooperation (p = .32).

The effect of different phases of synchrony on the synchrony effect

Synchronization of behaviour between individuals has been found to result in a variety of prosocial outcomes. The role of endorphins in vigorous synchronous activities (Cohen, Ejsmond-Frey, Knight, & Dunbar, 2010) may underlie these effects as endorphins have been implicated in social bonding (Dunbar & Shultz, 2010). Although research on synchronous behaviour has noted that there are two dominant phases of synchrony: in-phase and anti-phase (Marsh, Richardson, Baron, & Schmidt, 2006), research on the effect of synchrony on endorphins has only incorporated in-phase synchrony. The current study examined whether both phases of synchrony would generate the synchrony effect. Twenty-two participants rowed under three counterbalanced conditions - alone, in-phase synchrony and anti-phase synchrony. Endorphin release, as measured via pain threshold, was assessed before and after each session. Change in pain threshold during the in-phase synchrony session was significantly higher than either of the other two conditions. These results suggest that the synchrony effect may be specific to just in-phase synchrony, and that social presence is not a viable explanation for the effect of synchrony on pain threshold

Cardiorespiratory, endocrine and metabolic changes in ponies undergoing intravenous or inhalation anaesthesia

Six Welsh gelding ponies (weight 246 ± 6 kg) were premedicated with 0.03 mg/kg of acepromazine intravenously (i.v.) followed by 0.02 mg/kg of detomidine i.v. Anaesthesia was induced with 2 mg/kg of ketamine i.v. Ponies were intubated and lay in left lateral recumbency. On one occasion anaesthesia was maintained for 2 h using 1.2% halothane in oxygen. The same group of ponies were anaesthetized 1 month later using the same induction regime and anaesthesia was maintained with a combination of detomidine, ketamine and guaiphenesin, while the ponies breathed oxygen-enriched air. Electrocardiogram, heart rate, mean arterial blood pressure, cardiac output, respiratory rate, blood gases, temperature, haematocrit, glucose, lactate and cortisol were measured and cardiac index and systemic vascular resistance were calculated in both groups. Beta-endorphin, met-enkephalin, dynorphin, arginine vasopressin (AVP), adrenocorticotrophic hormone (ACTH) and catecholamines were measured in the halothane anaesthesia group only and 11-deoxycortisol during total intravenous anaesthesia (TIVA) only. Cardiorespiratory depression was more marked during halothane anaesthesia. Hyperglycaemia developed in both groups. Lactate and AVP increased during halothane anaesthesia. Cortisol increased during halothane and decreased during TIVA. There were no changes in the other hormones during anaesthesia. Recovery was smooth in both groups. TIVA produced better cardiorespiratory performance and suppressed the endocrine stress response observed during halothane anaesthesia.

Utilização da acupuntura no tratamento de cães com discopatia intervertebral

The intervertebral disc diseases have a high casuistic in clinical routines veterinary among dogs. These conditions can cause pain, paresis or paralysis of limbs depending on the degree of injury. Clinical signs are not limited to the intervertebral disc, other anatomical parts are included. In conventional medicine, treatment may be surgical or clinical, by the use of corticosteroids with muscle relaxants. Acupuncture was an alternative to treating these diseases due to its anti-inflammatory and analgesic effects. Although there are few studies for the treatment of discopathies, acupuncture triggers the release of substances such as dynorphins, beta-endorphins and serotonin, among others; that act inhibiting somatic and visceral pain. Electroacupuncture is used to potentiate the effects of acupuncture. It can be performed with different frequencies according to the clinical evolution. However there are different opinions related to the greater efficacy in relation to acupuncture. The restraint and monitoring of the treated animal are important factors for its recovery. The association between acupuncture and conventional treatment (surgical or clinical) achieved better results than acupuncture alone. This proves that acupuncture can be considered an option in order to minimize the complications of surgery or assist in patient recovery

Acupuncture as therapeutic resource in patient with bruxism

Bruxism is the harmful habit of clenching or grinding the teeth during the day and / or night, with unconscious pattern, with particular intensity and frequency, outside the functional movements of chewing and swallowing. It is accepted that bruxism is a response controlled by the neurotransmitters dopamine system associated with emotional component. The proposed of treatment of bruxism with acupuncture aims to stimulate sensory fibers of the peripheral nervous system leading to electrical transmission by neurons sufficient to produce changes in the central nervous system. As a consequence there is the release of substances (cortisol, endorphins, dopamine, noradrenaline and serotonin) that promote wellness and restoration of harmony, be it psychological, biological and / or behavioral.

Relatório de estágio em dermoneuromodulação no tratamento da dor

Mestrado em Fisioterapia