Pulmonary C-fiber activation attenuates respiratory-related tongue movements

Abstract

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.

Fig. 1.

Retrusive and protrusive tongue force induced by electrical stimulation of the hypoglossal (XII) nerve. Stimulation of the XII nerve resulted in retraction of the tongue when the nerve was intact and also following section of the medial branch (XII_MED). Protrusive tongue force was evoked in animals following section of the lateral XII branch (XII_LAT). The upward arrow indicates the time that the electrical stimulation was delivered to the XII nerve.

Fig. 2.

Representative examples of the tongue force and integrated diaphragm (Int Dia) activity in response to capsaicin administration in spontaneously breathing rats. The capsaicin was delivered during tracheal occlusion in rats with XII nerves intact (A), or following selective section of the XII_MED (B) or XII_LAT branches (C). During tracheal occlusion, retrusive tongue force progressively increased in both XII-intact and XII_MED-section rats. Protrusive tongue movement occurred in XII_LAT-section rats at ∼10 s after tracheal occlusion. The upward arrow indicates the time of capsaicin injection. The horizontal dotted line represents the period of airway occlusion. BP, blood pressure; au, arbitrary units.

Fig. 3.

Representative example showing the temporal relationship between the forces developed by tongue movements and the onset of the Int Dia burst. Tongue force could not be clearly observed during the baseline period of spontaneous breathing (left, “Pre-occlusion”). Following tracheal occlusion, the onset of retrusive tongue force in the XII_MED-sectioned rat and protrusive force in XII_LAT-sectioned rat occurred before the diaphragm burst (middle, “Occlusion”). In contrast, following capsaicin treatment (right, “Occlusion & Capsaicin”), the onset of the tongue force was delayed and occurred after the diaphragm burst.

Fig. 4.

Differential impact of pulmonary C-fiber activation on the peak response of tongue force and diaphragm activity during tracheal occlusion. Both doses of capsaicin significantly attenuated the tongue force in all groups, but did not significantly alter the diaphragm activity. Values are means ± SE. **P < 0.01 compared with the value during tracheal occlusion but without capsaicin treatment. ##P < 0.01, significant difference between response of the diaphragm and tongue force.

Fig. 5.

Effects of capsaicin administration on the tongue force in XII-intact (A), XII_MED-section (B), and XII_LAT-section (C) rats during tracheal occlusion. Both doses of capsaicin significantly attenuated the retrusive (A and B) and protrusive (C) tongue force. Values are means ± SE. *P < 0.05 and **P < 0.01 compared with the value during tracheal occlusion, but without capsaicin treatment.

Fig. 6.

Changes in the relative onset time of tongue force and diaphragm activity following capsaicin administration in XII-intact (A), XII_MED-sectioned (B), and XII_LAT-sectioned (C) rats. During tracheal occlusion, the onset of inspiratory-related tongue force occurred before the diaphragm burst, as reflected by negative value of the onset time. However, following both doses of capsaicin, the value of the force onset became positive, indicating that capsaicin delayed the inspiratory tongue force. Values are means ± SE. *P < 0.05 and **P < 0.01 compared with the value during tracheal occlusion, but without capsaicin treatment.