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Central Modulation of Pain
Published in Peter Kam, Ian Power, Michael J. Cousins, Philip J. Siddal, Principles of Physiology for the Anaesthetist, 2020
Peter Kam, Ian Power, Michael J. Cousins, Philip J. Siddal
A second tract that conveys nociceptive information is the spinoreticular tract (SRT), which terminates in the reticular formation of the medulla. The cells of origin of the spinoreticular tract are located in the deep layers of the dorsal horn and in laminae VII and VIII of the ventral horn. These cells send projections to several nuclei in the reticular formation such as the lateral reticular nucleus, nucleus gigantocellularis, nucleus paragigantocellularis lateralis in the medulla, the pontine nuclei oralis and caudalis and the parabrachial region. Many spinoreticular neurons are activated preferentially by noxious input, but there is no clear somatotopic organization of the SRTs. These projections terminate in close apposition to regions that are involved in blood pressure and motor control and the descending inhibition of pain. Therefore, it appears that this pathway is involved in the basic autonomic, motor and endogenous analgesic responses to nociceptive input. Central processing of this information may contribute to emotional responses associated with anxiety or threat.
Brainstem and Cardiovascular Regulation
Published in David Robertson, Italo Biaggioni, Disorders of the Autonomic Nervous System, 2019
Ching-Jiunn Tseng, Che-Se Tung
The LC sends projections rostrally from the pons to several areas, including those in which NA participates in blood pressure and fluid volume control (Bhaskaran and Freed, 1988). The LC receives both adrenergic input and excitatory amino acid input from the nucleus paragigantocellularis. The interactions with baroreceptors is suggested by the presence of fibers from the LC that terminate in the Al and A2 areas which in turn are linked to efferent baroreflex axes such as C1, C2, dorsal vagal nucleus and nucleus ambiguus. The LC may also be involved in the cardiovascular response that occurs after changes in blood volume such as moderate hemorrhage or changes in posture (Elam, Svensson and Thoren, 1985). Furthermore, a sustained natriuresis can be induced by cholinergic stimulation of the LC which is attenuated by lesions of the anterioventral third ventricle (De Luca et al., 1991). In short, this evidence indicates that the LC is involved in cardiovascular regulation.
Organization of Central Respiratory Neurons
Published in Alan D. Miller, Armand L. Bianchi, Beverly P. Bishop, Neural Control of the Respiratory Muscles, 2019
Armand L. Bianchi, Rosario Pásaro
Medullary structures other than the DRG and VRG have been proposed as playing a role in the generation and control of breathing. It has been suggested that the caudal portion of the nucleus paragigantocellularis lateralis (NPGL) was part of the respiratory CPG.26 This assertion was on the basis of neuroanatomical evidence (retrograde transport of HRP from VRG to NPGL),3 and focal cold block of the NPGL which caused reversible apnea.15 It is possible that the NPLG might be in the same area included in the 400-μm-thick slice of the pre-Bötzinger complex proposed by Smith et al.68 The NPGL also receives inputs from NTS, parabrachial nuclei in the rostral pons, hypothalamic nuclei, several reticular nuclei, and the contralateral NPGL.
Phase I and phase II clinical trials for the treatment of male sexual dysfunction—a systematic review of the literature
Published in Expert Opinion on Investigational Drugs, 2018
Paolo Capogrosso, Francesco Montorsi, Andrea Salonia
Trials investigating novel medical treatments for PE are reported in Table 3. Currently, dapoxetine is the only approved oral drug for the treatment of PE, although several SSRIs have been investigated and some of them are used as off-label compounds in PE patients [13]. The effect of SSRIs on ejaculation is based on the increased activity of serotonergic cells in the nucleus paragigantocellularis, which leads to the inhibition of the expulsion phase of ejaculation by modulating the bulbospongiosus muscle activity, and to the impairment of the emission phase by blocking the rise in seminal vesicle pressure [36]. Beside dapoxetine, the benefit of other SSRIs is controversial because of the pharmacokinetics and tolerability profile of these drugs [13]. Shin et al. have recently reported the results of a phase I trial investigating the safety of different doses of DA-8031, a new highly selective SSRIs [37]. Preclinical studies have shown that the low affinity of DA-8031 for other receptors may contribute to fewer side effects compared to other SSRIs [38]. The authors tested a single administration of seven different doses from 20 to 120 mg in 70 healthy men: results showed that the drug was well tolerated up to 80 mg, with the most frequent AE being nausea, reported by 11 cases, followed by orthostatic hypotension in nine cases. Given the previous evidence of QTc interval prolongation associated with SSRIs, the authors looked also at the ECG of treated patients: significant prolongation of the QTc interval was observed only with the 120 mg dose. In terms of pharmacokinetics, the drug showed a t1/2 of 17.9–28.7 h, which appears suitable for a once-daily regimen.