Suppressive influences from periaqueductal gray and nucleus raphe magnus on respiration and related reflex activities and on solitary tract neurons, and effect of naloxone

Sessle, Barry J.; Ball, G. J.; Lucier, Gregory E.

doi:10.1016/0006-8993(81)91283-x

Cited by 87 publications

(38 citation statements)

References 26 publications

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“…Galaninergic neurons possibly involved in this function could be localized in the NTS itself or in neural structures already proved to be engaged in the antinociceptive control, such as the medullary midline raphe nuclei or the periaqueductal grey (e.g., 38,62). To further support the parallel between nociception and cough, we can also mention that medullary raphe nuclei have a complex role in the generation of airway defensive reflexes including cough (e.g., 3, 24, 57) and that, in addition, suppressive influences from the periaqueductal grey and the nucleus raphe magnus on the cough reflex have been demonstrated (54). Interestingly, similarly to galanin-induced antinociception, these influences are in part mediated by opioids.…”

Section: Discussionmentioning

confidence: 88%

Inhibitory control of the cough reflex by galanin receptors in the caudal nucleus tractus solitarii of the rabbit

Mutolo

Cinelli

Bongianni

et al. 2014

American Journal of Physiology-Regulatory, Integrative and Comp

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The caudal nucleus tractus solitarii (NTS) is the main central station of cough-related afferents and a strategic site for the modulation of the cough reflex. The similarities between the characteristics of central processing of nociceptive and cough-related inputs led us to hypothesize that galanin, a neuropeptide implicated in the control of pain, could also be involved in the regulation of the cough reflex at the level of the NTS, where galanin receptors have been found. We investigated the effects of galanin and galnon, a nonpeptide agonist at galanin receptors, on cough responses to mechanical and chemical (citric acid) stimulation of the tracheobronchial tree. Drugs were microinjected (30 -50 nl) into the caudal NTS of pentobarbital sodium-anesthetized, spontaneously breathing rabbits. Galnon antitussive effects on cough responses to the mechanical stimulation of the airway mucosa via a custom-built device were also investigated. Bilateral microinjections of 1 mM galanin markedly decreased cough number, peak abdominal activity, and increased cough-related total cycle duration. Bilateral microinjections of 1 mM galnon induced mild depressant effects on cough, whereas bilateral microinjections of 10 mM galnon caused marked antitussive effects consistent with those produced by galanin. Galnon effects were confirmed by using the cough-inducing device. The results indicate that galanin receptors play a role in the inhibitory control of the cough reflex at the level of the caudal NTS and provide hints for the development of novel antitussive strategies. airway defensive reflexes; galanin; galanin receptors; galnon; nucleus tractus solitarii COUGH IS A VERY IMPORTANT airway protective reflex and is one of the most common reason why patients seek medical attention. Cough is purposeful and useful under many circumstances, but in case of persistent or chronic cough (e.g., 15) is without an apparent aim and benefit and can results in a wide range of physical and psychological complications including urinary incontinence, insomnia, depression, and anxiety. The efficacy of antitussive drugs is far from clear from the available evidence and, in addition, limited by important side effects. Therefore, further research to find better antitussive approaches is necessary (for reviews see Refs. 4 and 15). Studies undertaken to provide insights into the neural mechanisms subserving the cough reflex may also provide useful suggestions for novel antitussive therapeutic strategies. The cough reflex involves several brain stem structures that also underlie respiratory rhythm generation (e.g., 7,9,10,19,24,27,[47][48][49]55).In particular, the nucleus tractus solitarii (NTS), especially in its caudal aspects, is the main central terminus of cough-related afferents (14, 39 -41, 43, 53 also for further references) and, in addition, a possible strategic site of synaptic plasticity, where cough-related sensory inputs can be modulated (e.g., 10,14,34,39,40,43).In recent years, we and other researchers have focused our attention on the s...

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Section: Discussionmentioning

confidence: 88%

Inhibitory control of the cough reflex by galanin receptors in the caudal nucleus tractus solitarii of the rabbit

Mutolo

Cinelli

Bongianni

et al. 2014

American Journal of Physiology-Regulatory, Integrative and Comp

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“…Mu-opioid-receptor-mediated signaling within the PAG also elicits increases in heart rate and blood pressure (Keay et al 1997) and inhibits feeding evoked by hypothalamic stimulation (Jenck et al 1987). The suppression of respiratory-related discharge in cells of the nucleus tractus solitarius by raphe magnus stimulation is reversed by naloxone, suggestive of an opioid-receptor-mediated influence of VMM on respiration (Sessle et al 1981). It has even been reported that morphine microinjection into VMM or PAG elicits locomotor effects (immobility or wild running depending on the site of injection) more reliably than antinociception (Morgan and Whitney 2000; Morgan et al 1998).…”

Section: O P I O I D S I G N a L I N G I N V M M A N D P A G P A R T mentioning

confidence: 99%

Deconstructing Endogenous Pain Modulations

Mason

2005

Journal of Neurophysiology

129

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Mason, Peggy. Deconstructing endogenous pain modulation. J Neurophysiol 94: 1659Neurophysiol 94: -1663Neurophysiol 94: , 2005 doi:10.1152/jn.00249.2005. A pathway from the midbrain periaqueductal gray (PAG) through the ventromedial medulla (VMM) to the dorsal horn constitutes a putative endogenous nociceptive modulatory system. Yet activation of neurons in both PAG and VMM changes the responses of dorsal horn cells to nonnoxious stimuli and elicits motor and autonomic reactions that are not directly related to nociception. Activation of mu-opioid receptors in VMM and PAG also modifies processes in addition to nociceptive transmission. The descending projections of VMM neurons are not specific to nociception as VMM projects to the spinal superficial dorsal horn where thermoreceptors as well as nociceptors terminate. In addition, experiments with pseudorabies virus demonstrate multisynaptic pathways from VMM to sympathetic and parasympathetic target organs. VMM neurons respond to both noxious and unexpected innocuous stimuli of multiple modalities, and change their discharge during behaviors unrelated to pain such as micturition/continence and sleep/wake. In conclusion, all available evidence argues against the idea that PAG and VMM target nociception alone. Instead these brain stem sites may effect homeostatic adjustments made necessary by salient situations including but not limited to injury.

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“…In addition to its modulating influence on pain (Dunckley et al, 2005), the PAG, through opioidergic mechanisms, suppresses respiration (Sessle et al, 1981) via direct actions on the nucleus tractus solitarius in the ventral lateral medulla. The PAG is connected to the prefrontal cortex (Hadjipavlou et al, 2006), in which we have identified breath hold-related BOLD signal decreases.…”

Section: Opioid-sensitive Aspects Of the Breath Holdmentioning

confidence: 99%

Opioids Depress Cortical Centers Responsible for the Volitional Control of Respiration

Pattinson¹,

Governo²,

MacIntosh³

et al. 2009

Journal of Neuroscience

158

138

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Respiratory depression limits provision of safe opioid analgesia and is the main cause of death in drug addicts. Although opioids are known to inhibit brainstem respiratory activity, their effects on cortical areas that mediate respiration are less well understood. Here, functional magnetic resonance imaging was used to examine how brainstem and cortical activity related to a short breath hold is modulated by the opioid remifentanil. We hypothesized that remifentanil would differentially depress brain areas that mediate sensoryaffective components of respiration over those that mediate volitional motor control. Quantitative measures of cerebral blood flow were used to control for hypercapnia-induced changes in blood oxygen level-dependent (BOLD) signal. Awareness of respiration, reflected by an urge-to-breathe score, was profoundly reduced with remifentanil. Urge to breathe was associated with activity in the bilateral insula, frontal operculum, and secondary somatosensory cortex. Localized remifentanil-induced decreases in breath hold-related activity were observed in the left anterior insula and operculum. We also observed remifentanil-induced decreases in the BOLD response to breath holding in the left dorsolateral prefrontal cortex, anterior cingulate, the cerebellum, and periaqueductal gray, brain areas that mediate task performance. Activity in areas mediating motor control (putamen, motor cortex) and sensory-motor integration (supramarginal gyrus) were unaffected by remifentanil. Breath hold-related activity was observed in the medulla. These findings highlight the importance of higher cortical centers in providing contextual awareness of respiration that leads to appropriate modulation of respiratory control. Opioids have profound effects on the cortical centers that control breathing, which potentiates their actions in the brainstem.

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Suppressive influences from periaqueductal gray and nucleus raphe magnus on respiration and related reflex activities and on solitary tract neurons, and effect of naloxone

Cited by 87 publications

References 26 publications

Inhibitory control of the cough reflex by galanin receptors in the caudal nucleus tractus solitarii of the rabbit

Inhibitory control of the cough reflex by galanin receptors in the caudal nucleus tractus solitarii of the rabbit

Deconstructing Endogenous Pain Modulations

Opioids Depress Cortical Centers Responsible for the Volitional Control of Respiration

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