scholarly journals Pulmonary C-fiber activation attenuates respiratory-related tongue movements

2012 ◽  
Vol 113 (9) ◽  
pp. 1369-1376 ◽  
Author(s):  
Kun-Ze Lee ◽  
David D. Fuller ◽  
Ji-Chuu Hwang

The functional impact of pulmonary C-fiber activation on upper airway biomechanics has not been evaluated. Here, we tested the hypothesis that pulmonary C-fiber activation alters the respiratory-related control of tongue movements. The force produced by tongue movements was quantified in spontaneously breathing, anesthetized adult rats before and after stimulation of pulmonary C fibers via intrajugular delivery of capsaicin (0.625 and 1.25 μg/kg). Brief occlusion of the trachea was used to increase the respiratory drive to the tongue muscles, and hypoglossal (XII) nerve branches were selectively sectioned to denervate the protrusive and retrusive tongue musculature. Tracheal occlusion triggered inspiratory-related tongue retrusion in rats with XII nerves intact or following section of the medial XII nerve branch, which innervates the genioglossus muscle. Inspiratory-related tongue protrusion was only observed after section of the lateral XII branch, which innervates the primary tongue retrusor muscles. The tension produced by inspiratory-related tongue movement was significantly attenuated by capsaicin, but tongue movements remained retrusive, unless the medial XII branch was sectioned. Capsaicin also significantly delayed the onset of tongue movements such that tongue forces could not be detected until after onset of the inspiratory diaphragm activity. We conclude that altered neural drive to the tongue muscles following pulmonary C-fiber activation has a functionally significant effect on tongue movements. The diminished tongue force and delay in the onset of tongue movements following pulmonary C-fiber activation are potentially unfavorable for upper airway patency.

2012 ◽  
Vol 116 (1) ◽  
pp. 35-46 ◽  
Author(s):  
Matthias Eikermann ◽  
Martina Grosse-Sundrup ◽  
Sebastian Zaremba ◽  
Mark E. Henry ◽  
Edward A. Bittner ◽  
...  

Background Procedural sedation is frequently performed in spontaneously breathing patients, but hypnotics and opioids decrease respiratory drive and place the upper airway at risk for collapse. Methods In a randomized, controlled, cross-over, pharmaco-physiologic study in 12 rats, we conducted acute experiments to compare breathing and genioglossus electromyogram activity at equianesthetic concentrations of ketamine, a noncompetitive N-methyl-D-aspartate receptor antagonist that combines potent analgesic with hypnotic action effects, versus propofol. In 10 chronically instrumented rats resting in a plethysmograph, we measured these variables as well as electroencephalography during five conditions: quiet wakefulness, nonrapid-eye-movement sleep, rapid eye movement sleep, and low-dose (60 mg/kg intraperitoneally) and high-dose ketamine anesthesia (125 mg/kg intraperitoneally). Results Ketamine anesthesia was associated with markedly increased genioglossus activity (1.5 to fivefold higher values of genioglossus electromyogram) compared with sleep- and propofol-induced unconsciousness. Plethysmography revealed a respiratory stimulating effect: higher values of flow rate, respiratory rate, and duty-cycle (effective inspiratory time, 1.5-to-2-fold higher values). During wakefulness and normal sleep, the δ (f = 6.51, P = 0.04) electroencephalogram power spectrum was an independent predictor of genioglossus activity, indicating an association between electroencephalographic determinants of consciousness and genioglossus activity. Following ketamine administration, electroencephalogram power spectrum and genioglossus electroencephalogram was dissociated (P = 0.9 for the relationship between δ/θ power spectrum and genioglossus electromyogram). Conclusions Ketamine is a respiratory stimulant that abolishes the coupling between loss-of-consciousness and upper airway dilator muscle dysfunction in a wide dose-range. Ketamine compared with propofol might help stabilize airway patency during sedation and anesthesia.


1991 ◽  
Vol 71 (5) ◽  
pp. 1795-1800 ◽  
Author(s):  
S. B. Hollstien ◽  
M. L. Carl ◽  
E. S. Schelegle ◽  
J. F. Green

We examined the contribution of afferent vagal A- and C-fibers on abdominal expiratory muscle activity (EMA). In seven spontaneously breathing supine dogs anesthetized with alpha-chloralose we recorded the electromyogram of the external oblique muscle at various vagal temperatures before and after the induction of a pneumothorax. When myelinated fibers were blocked selectively by cooling the vagus nerves to 7 degrees C, EMA decreased to 40% of control (EMA at 39 degrees C). With further cooling to 0 degrees C, removing afferent vagal C-fiber activity, EMA returned to 72% of control. On rewarming the vagus nerves to 39 degrees C, we then induced a pneumothorax (27 ml/kg) that eliminated the EMA in all the dogs studied. Cooling the vagus nerves to 7 degrees C, during the pneumothorax, produced a slight though not significant increase in EMA. However, further cooling of the vagus nerves to 0 degrees C caused the EMA to return vigorously to 116% of control. In three dogs, intravenous infusion of a constant incrementally increasing dose of capsaicin, a C-fiber stimulant, decreased EMA in proportion to the dose delivered. These results suggest that EMA is modulated by a balance between excitatory vagal A-fiber activity, most likely from slowly adapting pulmonary stretch receptors, and inhibitory C-fiber activity, most likely from lung C-fibers.


2020 ◽  
Vol 128 (5) ◽  
pp. 1130-1145
Author(s):  
Hsiao-Sen Chang ◽  
Kun-Ze Lee

Tongue muscle activity plays an important role in the regulation of upper airway patency. This study aimed to investigate the respiratory activity of the extrinsic tongue muscle in response to capsaicin-induced bronchopulmonary C-fiber activation following cervical spinal cord contusion. Midcervical spinal-contused animals exhibited a greater baseline preinspiratory burst amplitude of the extrinsic tongue muscle and were resistant to inhaled capsaicin-induced reduction of respiratory tongue muscle activity at the acute injured stage. However, inhalation of capsaicin caused a more severe attenuation of preinspiratory activity of the extrinsic tongue muscle at the chronic injured stage. These results suggest that the upper airway may be predisposed to collapse in response to bronchopulmonary C-fiber activation following chronic cervical spinal cord injury.


1996 ◽  
Vol 75 (1) ◽  
pp. 298-310 ◽  
Author(s):  
C. L. Kwan ◽  
J. W. Hu ◽  
B. J. Sessle

1. The effects of C-fiber depletion induced by neonatal capsaicin treatment on the functional properties of low-threshold mechanoreceptive (LTM) neurons in the rat trigeminal (V) subnucleus oralis and nucleus principalis were examined. Neonatal rats were injected with capsaicin within 48 h of birth. The mechanoreceptive field (RF) and response properties of 184 oralis LTM neurons and 185 principalis LTM neurons were studied in adult capsaicin-treated rats. These properties were compared with those of 200 oralis LTM neurons and 253 principalis LTM neurons from untreated or vehicle-treated (control) adult rats. 2. The effectiveness of neonatal capsaicin in depleting C fibers was tested by determining the plasma extravasation of Evans blue dye that was induced in the hindlimb skin by the cutaneous application of the C-fiber excitant and inflammatory irritant mustard oil. The amount of extravasation in capsaicin-treated rats was significantly less than that of control rats. 3. Neonatal capsaicin treatment was associated with significant increases in neuronal RF size and in the percentage of neurons with convergent inputs from more than one type of peripheral tissue (e.g., nonsinus hair, vibrissae, glabrous skin/mucosa, subcutaneous structures such as joint or muscle, periodontal ligament) in both subnucleus oralis and nucleus principalis. In subnucleus oralis, neonatal capsaicin treatment produced a significant increase in the percentage of neurons with a RF involving both V1 and V2 divisions, and a significant decrease in the percentage of neurons with a RF restricted to the V1 division. Analogous changes were not observed in nucleus principalis, although for principalis vibrissa-sensitive neurons, neonatal capsaicin treatment was associated with significant increases in the total number of vibrissae per neuronal RF and in the maximal length of the vibrissal row (i.e., the number of vibrissae in the longest row of vibrissae, stimulation of which was effective in activating a given neuron). 4. Neonatal capsaicin treatment did not significantly affect other oralis or principalis neuronal properties, including the percentage of neurons exhibiting spontaneous activity or abnormal response properties (such as habituating tap sensitivity, discontinuous RF, or mixed adaptation properties within the RF). 5. The changes in the functional properties of oralis and principalis LTM neurons induced by neonatal capsaicin treatment are consistent with those previously reported at other levels of the rodent CNS. They provide additional support to the view that C fibers may have an important role in shaping the functional properties of central LTM somatosensory neurons.


2015 ◽  
Vol 118 (4) ◽  
pp. 489-494 ◽  
Author(s):  
Jonathan Cheetham ◽  
Amanda Jones ◽  
Manuel Martin-Flores

Hypercapnia produces a profound effect on respiratory drive and upper airway function to maintain airway patency. Previous work has evaluated the effects of hypercapnia on the sole arytenoid abductor, the posterior cricoarytenoid (PCA), using indirect measures of function, such as electromyography and direct nerve recording. Here we describe a novel method to evaluate PCA function in anesthetized animals and use this method to determine the effects of hypercapnia on PCA function. Eight dogs were anesthetized, and a laryngeal mask airway was used, in combination with high-speed videoendoscopy, to evaluate laryngeal function. A stepwise increase in inspired partial pressure of CO2 produced marked arytenoid abduction above 70-mmHg end-tidal CO2 (ETCO2) ( P < 0.001). Glottic length increased above 80-mmHg ETCO2 ( P < 0.02), and this lead to underrepresentation of changes in glottic area, if standard measures of glottic area (normalized glottic gap area) were used. Use of a known scale to determine absolute glottic area demonstrated no plateau with increasing ETCO2 up to 120 mmHg. Ventilatory parameters also continued to increase with no evidence of a maximal response. In a second anesthetic episode, repeated bursts of transient hypercapnia for 60 s with an ETCO2 of 90 mmHg produced a 43–55% increase in glottic area ( P < 0.001) at or shortly after the end of the hypercapnic burst. A laryngeal mask airway can be used in combination with videoendoscopy to precisely determine changes in laryngeal dimensions with high temporal resolution. Absolute glottic area more precisely represents PCA function than normalized glottic gap area at moderate levels of hypercapnia.


2019 ◽  
Vol 122 (2) ◽  
pp. 616-631 ◽  
Author(s):  
Jason M. White ◽  
Hyun Joon Lee ◽  
Patrick Malone ◽  
Stephen P. DeWeerth ◽  
Keith E. Tansey

The cutaneus trunci muscle (CTM) reflex produces a skin “shrug” in response to pinch on a rat’s back through a three-part neural circuit: 1) A-fiber and C-fiber afferents in segmental dorsal cutaneous nerves (DCNs) from lumbar to cervical levels, 2) ascending propriospinal interneurons, and 3) the CTM motoneuron pool located at the cervicothoracic junction. We recorded neurograms from a CTM nerve branch in response to electrical stimulation. The pulse trains were delivered at multiple DCNs (T6–L1), on both sides of the midline, at two stimulus strengths (0.5 or 5 mA, to activate Aδ fibers or Aδ and C fibers, respectively) and four stimulation frequencies (1, 2, 5, or 10 Hz) for 20 s. We quantified both the temporal dynamics (i.e., latency, sensitization, habituation, and frequency dependence) and the spatial dynamics (spinal level) of the reflex. The evoked responses were time-windowed into Early, Mid, Late, and Ongoing phases, of which the Mid phase, between the Early (Aδ fiber mediated) and Late (C fiber mediated) phases, has not been previously identified. All phases of the response varied with stimulus strength, frequency, history, and DCN level/side stimulated. In addition, we observed nociceptive characteristics like C fiber-mediated sensitization (wind-up) and habituation. Finally, the range of latencies in the ipsilateral responses were not very large rostrocaudally, suggesting a myelinated neural path within the ipsilateral spinal cord for at least the A fiber-mediated Early-phase response. Overall, these results demonstrate that the CTM reflex shares the temporal dynamics in other nociceptive reflexes and exhibits spatial (segmental and lateral) dynamics not seen in those reflexes. NEW & NOTEWORTHY We have physiologically studied an intersegmental reflex exploring detailed temporal, stimulus strength-based, stimulation history-dependent, lateral and segmental quantification of the reflex responses to cutaneous nociceptive stimulations. We found several physiological features in this reflex pathway, e.g., wind-up, latency changes, and somatotopic differences. These physiological observations allow us to understand how the anatomy of this reflex may be organized. We have also identified a new phase of this reflex, termed the “mid” response.


2006 ◽  
Vol 101 (5) ◽  
pp. 1377-1385 ◽  
Author(s):  
E. Fiona Bailey ◽  
Yu-Hsien Huang ◽  
Ralph F. Fregosi

We recently showed respiratory-related coactivation of both extrinsic and intrinsic tongue muscles in the rat. Here, we test the hypothesis that intrinsic tongue muscles contribute importantly to changes in velopharyngeal airway volume. Spontaneously breathing anesthetized rats were placed in a MRI scanner. A catheter was placed in the hypopharynx and connected to a pressure source. Axial and sagittal images of the velopharyngeal airway were obtained, and the volume of each image was computed at airway pressures ranging from +5.0 to −5.0 cmH2O. We obtained images in the hypoglossal intact animal (i.e., coactivation of intrinsic and extrinsic tongue muscles) and after selective denervation of the intrinsic tongue muscles, with and without electrical stimulation. Denervation of the intrinsic tongue muscles reduced velopharyngeal airway volume at atmospheric and positive airway pressures. Electrical stimulation of the intact hypoglossal nerve increased velopharyngeal airway volume; however, when stimulation was repeated after selective denervation of the intrinsic tongue muscles, the increase in velopharyngeal airway volume was significantly attenuated. These findings support our working hypothesis that intrinsic tongue muscles play a critical role in modulating upper airway patency.


SLEEP ◽  
2019 ◽  
Vol 43 (6) ◽  
Author(s):  
Olga Dergacheva ◽  
Thomaz Fleury-Curado ◽  
Vsevolod Y Polotsky ◽  
Matthew Kay ◽  
Vivek Jain ◽  
...  

Abstract Obstructive sleep apnea (OSA) is a common disorder characterized by repetitive sleep-related losses of upper airway patency that occur most frequently during rapid eye movement (REM) sleep. Hypoglossal motoneurons play a key role in regulating upper airway muscle tone and patency during sleep. REM sleep activates GABA and glycine neurons in the ventral medulla (VM) to induce cortical desynchronization and skeletal muscle atonia during REM sleep; however, the role of this brain region in modulating hypoglossal motor activity is unknown. We combined optogenetic and chemogenetic approaches with in-vitro and in-vivo electrophysiology, respectfully, in GAD2-Cre mice of both sexes to test the hypothesis that VM GABA/glycine neurons control the activity of hypoglossal motoneurons and tongue muscles. Here, we show that there is a pathway originating from GABA/glycine neurons in the VM that monosynaptically inhibits brainstem hypoglossal motoneurons innervating both tongue protruder genioglossus (GMNs) and retractor (RMNs) muscles. Optogenetic activation of ChR2-expressing fibers induced a greater postsynaptic inhibition in RMNs than in GMNs. In-vivo chemogenetic activation of VM GABA/glycine neurons produced an inhibitory effect on tongue electromyographic (EMG) activity, decreasing both the amplitude and duration of inspiratory-related EMG bursts without any change in respiratory rate. These results indicate that activation of GABA/glycine neurons from the VM inhibits tongue muscles via a direct pathway to both GMNs and RMNs. This inhibition may play a role in REM sleep associated upper airway obstructions that occur in patients with OSA.


2006 ◽  
Vol 100 (6) ◽  
pp. 1918-1927 ◽  
Author(s):  
Dale R. Bergren

Airway hyperresponsiveness is a cardinal feature of asthma. Lung C-fiber activation induces central and local defense reflexes that may contribute to airway hyperresponsiveness. Initial studies show that substance P (SP) activates C fibers even though it is produced and released by these same C fibers. SP may induce release of other endogenous mediators. Bradykinin (BK) is an endogenous mediator that activates C fibers. The hypothesis was tested that SP activates C fibers via BK release. Guinea pigs were anesthetized, and C-fiber activity (FA), pulmonary insufflation pressure (PIP), heart rate, and arterial blood pressure were monitored before and after intravenous injection of capsaicin (Cap), SP, and BK. Identical agonist challenges were repeated after infusion of an antagonist cocktail of des-Arg9-[Leu8]-BK (10−3 M, B1 antagonist), and HOE-140 (10−4 M, B2 antagonist). After antagonist administration, BK increased neither PIP nor FA. Increases in neither PIP nor FA were attenuated after Cap or SP challenge. In a second series of experiments, Cap and SP were injected before and after infusion of indomethacin (1 mg/kg iv) to determine whether either agent activates C fibers through release of arachidonic acid metabolites. Indomethacin administration decreased the effect of SP challenge on FA but not PIP. The effect of Cap on FA or PIP was not altered by indomethacin. In subsequent experiments, C fibers were activated by prostaglandin E2 and F2α. Therefore, exogenously applied SP stimulates an indomethacin-sensitive pathway leading to C-fiber activation.


2007 ◽  
Vol 97 (1) ◽  
pp. 933-936 ◽  
Author(s):  
E. Fiona Bailey ◽  
Amber D. Rice ◽  
Andrew J. Fuglevand

The tongue participates in a range of complex oromotor behaviors, including mastication, swallowing, respiration, and speech. Previous electromyographic studies of the human tongue have focused on respiratory-related tongue muscle activities and their role in maintaining upper airway patency. Remarkably, the activities of human hypoglossal motor units have not been studied during the execution of voluntary maneuvers. We recorded single motor unit activity using tungsten microelectrodes in the genioglossus muscle of 10 healthy human subjects performing both slow tongue protrusions and a static holding maneuver. Displacement of the tongue was detected by an isotonic transducer coupled to the lingual surface through a customized lever arm. For protrusion trials, the firing rate at recruitment was 13.1 ± 3 Hz and increased steeply to an average of 24 ± 6 Hz, often with very modest increases in tongue protrusion. For the static holding task, the average firing rate was 16.1 ± 4 Hz, which is surprisingly high relative to limb motor units. The average coefficient of variation of interspike intervals was ∼20% (range, 10–28%). These are the first recordings of their type obtained in human subjects and provide an initial glimpse into the voluntary control of hypoglossal motoneurons during tongue movements presumably instigated by activity in the motor cortex.


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