Intralaryngeal application of ATP evokes apneic response mainly via acting on P2X3 (P2X2/3) receptors of the superior laryngeal nerve in postnatal rats

Author(s):  
Jianguo Zhuang ◽  
Xiuping Gao ◽  
Wan Wei ◽  
Amir Pelleg ◽  
Fadi Xu

Aerosolized adenosine 5'-triphosphate (ATP) induces cough and bronchoconstriction by activating vagal sensory fibers' P2X3 and P2X2/3 receptors (P2X3R and P2X2/3R). The goal of this study is to determine the effect of these receptors on the superior laryngeal nerve (SLN)-mediated cardiorespiratory responses to ATP challenge. We compared the cardiorespiratory responses to intralaryngeal perfusion of either ATP or α,β-methylene ATP in rat pups before and after 1) intralaryngeal perfusion of A-317491 (a P2X3R and P2X2/3R antagonist); 2) bilateral section of the SLN; and 3) peri-SLN treatment with capsaicin (to block conduction in superior laryngeal C-fibers, SLCFs) or A-317491. The immunoreactivity (IR) of P2X3R and P2X2R was determined in laryngeal sensory neurons of the nodose/jugular ganglia. Lastly, a whole-cell patch clamp recording was used to determine ATP- or α,β-mATP-induced currents without and with A-317491 treatment. It was found that intralaryngeal perfusion of both ATP and α,β-mATP induced immediate apnea, hypertension, and bradycardia. The apnea was eliminated and the hypertension and bradycardia were blunted by intralaryngeal perfusion of A-317491 and peri-SLN treatment with either A-317491 or capsaicin, while all of the cardiorespiratory responses were abolished by bilateral section of the SLN. P2X3R- and P2X2R-IR were observed in nodose and jugular ganglionic neurons labeled by fluoro-gold (FG). ATP- and α,β-mATP-induced currents recorded in laryngeal C-neurons were reduced by 75% and 95% respectively by application of A-317491. It is concluded that in anesthetized rat pups, the cardiorespiratory responses to intralaryngeal perfusion of either ATP or α,β-mATP are largely mediated by activation of SLCFs' P2X3R-P2X2/3R.

2019 ◽  
pp. 014556131988615 ◽  
Author(s):  
Antonio Minni ◽  
Davide Rosati ◽  
Carlo Cavaliere ◽  
Massimo Ralli ◽  
Giulio Sementilli ◽  
...  

Background: Total thyroidectomy (TT) and completion thyroidectomy (CT) are two common surgical operations that are frequently followed by vocal symptoms despite preservation of the recurrent laryngeal nerve (RLN) and of the external branch of superior laryngeal nerve (EBSLN). The aim of this study was to analyze vocal alterations through endoscopic findings, videolaryngostroboscopy (VLS), acoustic vocal parameters and impact on patients’ quality of life after surgery in the absence of laryngeal nerve injury. Methods: We enrolled 198 patients who underwent thyroidectomy by the same surgeon. One hundred twenty-six patients underwent TT (group TT) while 72 underwent CT (group CT). All patients underwent preoperative VLS and Voice Handicap Index (VHI) assessment and postoperative VHI, VLS and Acoustic Voice Analysis with Multidimensional Voice Program Analysis 12 to 18 months after surgery. Results: We observed a statistically significant higher rate of EBSLN injury in CT compared to TT. Even in the absence of RLN and EBSLN injury, patients who underwent TT and CT presented slightly worse acoustic vocal parameters and VHI scores compared to healthy controls. Interestingly, some acoustic vocal parameters and VHI scores were significantly worse in group CT compared to group TT. Conclusions: The higher rate of EBSLN injury in CT rather than in TT suggests a higher surgical risk in CT. The vocal parameters of loudness and self-perception of voice were significantly worse after CT, suggesting a larger trauma in patients’ vocal outcome in CT if compared to TT, although these alterations were not reported as psychologically limiting daily life of patients. Nevertheless, the existence of multiple factors contributing to vocal alterations after thyroidectomy highlight the importance of a routine comprehensive functional voice analysis before and after surgery.


1989 ◽  
Vol 108 (5-6) ◽  
pp. 469-477 ◽  
Author(s):  
Siw Domeij ◽  
Bengt Carlsöö ◽  
Åke Dahlqvist ◽  
Sten Hellströ ◽  
Harry Kourtopoulos

2001 ◽  
Vol 90 (4) ◽  
pp. 1570-1576 ◽  
Author(s):  
Jalal M. Abu-Shaweesh ◽  
Ismail A. Dreshaj ◽  
Musa A. Haxhiu ◽  
Richard J. Martin

Stimulation of the superior laryngeal nerve (SLN) results in apnea in animals of different species, the mechanism of which is not known. We studied the effect of the GABAA receptor blocker bicuculline, given intravenously and intracisternally, on apnea induced by SLN stimulation. Eighteen 5- to 10-day-old piglets were studied: bicuculline was administered intravenously to nine animals and intracisternally to nine animals. The animals were anesthetized and then decerebrated, vagotomized, ventilated, and paralyzed. The phrenic nerve responses to four levels of electrical SLN stimulation were measured before and after bicuculline. SLN stimulation caused a significant decrease in phrenic nerve amplitude, phrenic nerve frequency, minute phrenic activity, and inspiratory time ( P < 0.01) that was proportional to the level of electrical stimulation. Increased levels of stimulation were more likely to induce apnea during stimulation that often persisted beyond cessation of the stimulus. Bicuculline, administered intravenously or intracisternally, decreased the SLN stimulation-induced decrease in phrenic nerve amplitude, minute phrenic activity, and phrenic nerve frequency ( P < 0.05). Bicuculline also reduced SLN-induced apnea and duration of poststimulation apnea ( P < 0.05). We conclude that centrally mediated GABAergic pathways are involved in laryngeal stimulation-induced apnea.


2006 ◽  
Vol 100 (1) ◽  
pp. 60-66 ◽  
Author(s):  
Rurong Wang ◽  
Fadi Xu ◽  
Jianguo Zhuang ◽  
Cancan Zhang

The carotid sinus nerve (CSN), important in cardiorespiratory modulation, mainly contains C fibers (CSCFs). Previous studies have demonstrated that selective stimulation of bronchopulmonary C fibers (PCFs) via right atrial injection of capsaicin (Cap; ∼0.25 μg) results in an apnea (∼3 s) associated with hypotension and bradycardia. The present study was undertaken to determine the effects of activating CSCFs on cardiorespiratory activities. Intracarotid injection of Cap was performed before and after bilateral transection of the CSN in anesthetized and spontaneously breathing rats. Our results showed that 1) low doses of Cap (up to 2 ng) produced an increase in minute ventilation by elevating both tidal volume and respiratory frequency with the threshold dosage at 1.0 ng ( P < 0.05); 2) high doses (4–64 ng) generated an apnea (prolongation of expiratory duration by ∼8-fold) and hypertension ( P < 0.05); 3) bilateral transection of the CSN reduced excitatory and inhibitory respiratory responses by 30 and 81%, respectively, and increased the hypertension by 88% ( P < 0.05); and 4) the same doses of Cap delivered into the right atrium to stimulate PCFs failed to evoke detectable cardiorespiratory responses. Our results suggest that compared with PCFs, CSCFs are more sensitive to Cap stimulation and that activation of these fibers significantly modulates cardiorespiratory activity in anesthetized rats.


2019 ◽  
Vol 98 (8) ◽  
pp. 500-503
Author(s):  
Akina Tamaki ◽  
Jason Thuener ◽  
Mark Weidenbecher

Superior laryngeal nerve neuralgia (SLNN) is an anterior neck pain syndrome that is underrecognized and, as a result, is often misdiagnosed. We present a series of patients who were diagnosed with and subsequently treated for SLNN. Nineteen patients were treated with oral nonsteroidal anti-inflammatory drugs (NSAIDs) and/or a therapeutic neck injection with 2% lidocaine and 40% triamcinolone acetonide. All patients completed a visual analog scale (VAS) to rate the level of pain before and after treatment. Four patients rated their pain as mild, 14 as moderate, and 1 as severe according to the VAS. Of the 19 patients, 8 chose to proceed with a 2-week course of NSAIDs and only 1 of them had complete resolution of their symptoms. A total of 18 patients underwent therapeutic neck injections, with a complete response to injection therapy in 10 patients. Five patients described a minimal residual foreign body sensation and 3 patients complained of mild residual pain. In this study, we found that therapeutic neck injections are effective not only in confirming the diagnosis but also in treating pain.


1988 ◽  
Vol 12 (4) ◽  
pp. 522-526 ◽  
Author(s):  
Svante Jansson ◽  
Lars -Erik Tisell ◽  
Ingrid Hagne ◽  
Esbjörn Sanner ◽  
Rune Stenborg ◽  
...  

2002 ◽  
Vol 93 (5) ◽  
pp. 1622-1629 ◽  
Author(s):  
Richard D. Andreatta ◽  
Eric A. Mann ◽  
Christopher J. Poletto ◽  
Christy L. Ludlow

Laryngeal adductor responses (LAR) close the airway in response to stimulation of peripheral afferents in the superior laryngeal nerve. Although both mucosal afferents and proprioceptive receptors are present in the larynx, their relative contribution for reflex elicitation is unknown. Our purpose was to determine which receptor types are of importance in eliciting the LAR. A servomotor with displacement feedback was used to deliver punctate displacements to the body of the arytenoid cartilage and overlying mucosa on each side of the larynx in eight anesthetized cats. The same displacements were delivered both before and after surgical excision of the overlying mucosa. With the mucosa intact, early short-latency component R1 LAR responses recorded from the thyroarytenoid muscles were frequent (ipsilateral > 92%, contralateral > 95%). After the mucosa was removed, the LAR became infrequent (<3%) and was reduced in amplitude in both the ipsilateral and contralateral thyroarytenoid muscle recording sites ( P < 0.0005). These findings demonstrate that mucosal mechanoreceptors and not proprioceptive afferents contribute to the elicitation of LAR responses in the cat.


2020 ◽  
Vol 318 (1) ◽  
pp. L89-L97
Author(s):  
Wan Wei ◽  
Xiuping Gao ◽  
Lei Zhao ◽  
Jianguo Zhuang ◽  
Yang Jiao ◽  
...  

Liquiritin apioside (LA), a main flavonoid component of licorice, reportedly suppresses cough responses to inhalation of aerosolized capsaicin [CAP; a stimulant to transient receptor potential vanilloid 1 (TRPV1)] in conscious guinea pigs via acting on peripheral nerves. However, the evidence of LA having a direct effect on airway sensory fibers is lacking. Considering the important role laryngeal chemoreceptors and mechanoreceptors play in triggering apnea and cough, we studied whether LA suppressed the apneic responses to stimulation of these receptors via directly acting on the superior laryngeal nerve (SLN). Intralaryngeal delivery of chemical [CAP, HCl, and distilled water (DW)] and mechanical [an air-pulse (AP)] stimulations was applied in anesthetized rat pups to evoke the apnea. These stimuli were repeated after intralaryngeal LA treatment or peri-SLN LA treatment to determine the direct effect of LA on the SLN. Our results showed that all stimuli triggered an immediate apnea. Intralaryngeal LA treatment significantly attenuated the apneic response to chemical but not mechanical stimulations. The same attenuation was observed after peri-SLN LA treatment. Owing that TRPV1 receptors of laryngeal C fibers are responsible for the CAP-triggered apneas, the LA impact on the activity of laryngeal C neurons retrogradely traced by DiI was subsequently studied using a patch-clamp approach. LA pretreatment significantly altered the electrophysiological kinetics of CAP-induced currents in laryngeal C neurons by reducing their amplitudes, increasing the rise times, and prolonging the decay times. In conclusion, our results, for the first time, reveal that LA suppresses the laryngeal chemoreceptor-mediated apnea by directly acting on the SLN (TRPV1 receptors of laryngeal C fibers).


2007 ◽  
Vol 103 (5) ◽  
pp. 1864-1872 ◽  
Author(s):  
Luxi Xia ◽  
Tracey Damon ◽  
Mary M. Niblock ◽  
Donald Bartlett ◽  
J. C. Leiter

The laryngeal chemoreflex (LCR) is elicited by water in the larynx and leads to apnea and respiratory disruption in immature animals. The LCR is exaggerated by the elevation of brain temperature within or near the nucleus of the solitary tract (NTS) in decerebrate piglets. Thermal prolongation of reflex apnea elicited by superior laryngeal nerve stimulation is reduced by systemic administration of GABAA receptor antagonists. Therefore, we tested the hypothesis that microdialysis within or near the NTS of gabazine, a GABAA receptor antagonist, would reverse thermal prolongation of the LCR. We examined this hypothesis in 21 decerebrate piglets (age 3–13 days). We elicited the LCR by injecting 0.1 ml of water into the larynx before and after each piglet's body temperature was elevated by ∼2.5°C and before and after 2–5 mM gabazine was dialyzed unilaterally and focally in the medulla. Elevated body temperature failed to prolong the LCR in one piglet, which was excluded from analysis. Elevated body temperature prolonged the LCR in all the remaining animals, and dialysis of gabazine into the region near the NTS ( n = 10) reversed the thermal prolongation of the LCR even though body temperature remained elevated. Dialysis of gabazine in other medullary sites ( n = 10) did not reverse thermal prolongation of the LCR. Gabazine had no consistent effect on baseline respiratory activity during hyperthermia. These findings are consistent with the hypothesis that hyperthermia activates GABAergic mechanisms in or near the NTS that are necessary for the thermal prolongation of the LCR.


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