Intranodose ganglion injections of dronabinol attenuate serotonin-induced apnea in Sprague-Dawley rat

Calik, Michael W.; Radulovački, Miodrag; Carley, David W.

doi:10.1016/j.resp.2013.10.001

Cited by 31 publications

(42 citation statements)

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“…This may reflect inhibition of afferent vagal nerve activity, leading to disinhibition of upper airway motor neurons. A recent report showing increased phasic activation of genioglossi, and attenuated serotonin-induced apnea in rats subjected to local nodose ganglion injections of dronabinol supports this interpretation 89. There were no serious adverse events associated with daily oral dronabinol.…”

Section: Drug Treatmentmentioning

confidence: 68%

Innovative treatments for adults with obstructive sleep apnea

Weaver¹,

Calik²,

Farabi³

et al. 2014

NSS

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Obstructive sleep apnea (OSA) affects one in five adult males and is associated with significant comorbidity, cognitive impairment, excessive daytime sleepiness, and reduced quality of life. For over 25 years, the primary treatment has been continuous positive airway pressure, which introduces a column of air that serves as a pneumatic splint for the upper airway, preventing the airway collapse that is the physiologic definition of this syndrome. However, issues with patient tolerance and unacceptable levels of treatment adherence motivated the exploration of other potential treatments. With greater understanding of the physiologic mechanisms associated with OSA, novel interventions have emerged in the last 5 years. The purpose of this article is to describe new treatments for OSA and associated complex sleep apnea. New approaches to complex sleep apnea have included adaptive servoventilation. There is increased literature on the contribution of behavioral interventions to improve adherence with continuous positive airway pressure that have proven quite effective. New non-surgical treatments include oral pressure devices, improved mandibular advancement devices, nasal expiratory positive airway pressure, and newer approaches to positional therapy. Recent innovations in surgical interventions have included laser-assisted uvulopalatoplasty, radiofrequency ablation, palatal implants, and electrical stimulation of the upper airway muscles. No drugs have been approved to treat OSA, but potential drug therapies have centered on increasing ventilatory drive, altering the arousal threshold, modifying loop gain (a dimensionless value quantifying the stability of the ventilatory control system), or preventing airway collapse by affecting the surface tension. An emerging approach is the application of cannabinoids to increase upper airway tone.

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Section: Drug Treatmentmentioning

confidence: 68%

Innovative treatments for adults with obstructive sleep apnea

Weaver¹,

Calik²,

Farabi³

et al. 2014

NSS

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“…5-HT activates 5-HT 3 receptors on the nodose ganglia that contribute to the Bezold-Jarisch reflex of bradycardia, hypotension, and apnea. 11,17-19 Intranodose ganglia injections of dronabinol activate inhibitory CB receptors, or allosterically modulates 5-HT 3 receptors that inhibit the 5-HT-induced excitation of the vagus nerve. 16,17,20,22 Before (Figure 1, top panel ) and after (Figure 1, middle panel ) neck surgery infusion of 5-HT (Figure 1, indicted by red line ) elicits an apneic response seen as a lack of abdomen movement measured by the piezoelectric strain gauge.…”

Section: Representative Resultsmentioning

confidence: 99%

“…The nodose ganglia of the vagus nerve contain a diverse array of receptors for amino acids, monoamines, neuropeptides, and other neurochemicals. 1 Intranodose ganglia injections of neurochemicals for those receptors to modify the activity of the vagus nerve have been done before, 16,17 and represent an excellent experimental model to elucidate peripheral pharmacological effects on the vagus nerve that can modify diseases such as sleep apnea, gastroesophageal reflux disease, or chronic cough. 2-4 …”

Section: Discussionmentioning

confidence: 99%

“…5 Previous experimental manipulations of the nodose ganglia involved electrophysiological recordings, 6 injections of immunohistochemical or immunofluorescent compounds for nerve tracings, 7-10 superfusion or injections of neuroexcitotoxins, 11-13 injections of adeno-associated virus to knockdown receptors, 14,15 and injections of receptor-specific neurochemicals to change the activity of the vagus nerve. 16,17 …”

Section: Introductionmentioning

confidence: 99%

“…Stimulation of serotonin type 3 (5-HT 3 ) receptors on nodose ganglia by intravenous (IV) infusion of serotonin (5-HT) induces the Bezold-Jarisch reflex, a vagal response trifecta of bradycardia, hypotension, and apnea, which can be abolished by supranodose vagatomy. 11,17-19 Apnea is easily measured by placing a respiratory transducer around the abdomen of the rat. 17,18 Cannabinoids decrease 5-HT-induced current in nodose ganglia cells, 20 and intranodose ganglia injections of dronabinol attenuate 5-HT-induced apnea.…”

Section: Introductionmentioning

confidence: 99%

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A Method of Nodose Ganglia Injection in Sprague-Dawley Rat

Calik

Radulovački

Carley

2014

JoVE

Self Cite

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Afferent signaling via the vagus nerve transmits important general visceral information to the central nervous system from many diverse receptors located in the organs of the abdomen and thorax. The vagus nerve communicates information from stimuli such as heart rate, blood pressure, bronchopulmonary irritation, and gastrointestinal distension to the nucleus of solitary tract of the medulla. The cell bodies of the vagus nerve are located in the nodose and petrosal ganglia, of which the majority are located in the former. The nodose ganglia contain a wealth of receptors for amino acids, monoamines, neuropeptides, and other neurochemicals that can modify afferent vagus nerve activity. Modifying vagal afferents through systemic peripheral drug treatments targeted at the receptors on nodose ganglia has the potential of treating diseases such as sleep apnea, gastroesophageal reflux disease, or chronic cough. The protocol here describes a method of injection neurochemicals directly into the nodose ganglion. Injecting neurochemicals directly into the nodose ganglia allows study of effects solely on cell bodies that modulate afferent nerve activity, and prevents the complication of involving the central nervous system as seen in systemic neurochemical treatment. Using readily available and inexpensive equipment, intranodose ganglia injections are easily done in anesthetized Sprague-Dawley rats.

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