The Physiology of Respiratory Sensations

Efferent-Reafferent Dissociation: The Relationship Between Neural Output from the Controller and the Response of the Ventilatory Pump

When a neural signal is generated from the controller and sent to the ventilatory muscles, we describe the message as an efferent neural impulse. When the ventilatory muscles contract in response to the signal, a flow of air is generated, the lungs and chest wall expand, and receptors throughout the ventilatory pump are stimulated. Flow, volume displacement, muscle tension, and joint position are all monitored by the body by virtue of stimulation of receptors in the lungs and chest wall and the messages sent back to the sensory cortex, messages we term afferent neural impulses.

When the efferent impulses and the response of the ventilatory pump, as evidenced by the reafferent activity of receptors throughout the lungs and chest wall (termed reafferent because it is in response to the original outgoing motor command), appear to be appropriate, we generally experience little breathing discomfort. However, when there is mismatch of the outgoing and incoming signals, or efferent–reafferent dissociation, the intensity of sensations such as air hunger and the effort or work of breathing increase. This notion was first introduced as the concept of length–tension inappropriateness to signify that under conditions of increased airflow obstruction, the ventilatory muscles generate greater tension with less shortening than in the normal state¹¹. Others have used the term neuromechanical dissociation to signify the mismatch between the efferent signals from the controller and the subsequent performance of the ventilatory pump¹². We prefer the concept of efferent–reafferent dissociation because it is more inclusive¹³. The model allows for input from a vast array of receptors in the upper airways, lower airways, pulmonary parenchyma, and chest wall in the modification of the intensity of dyspnea, and there are increasing experimental data to support this model^14,15.

In our discussion of the controller in Chapter 6, we noted that one of the unique features of the respiratory system is that it was under both voluntary and reflex control. Without thinking about our breathing, the brainstem respiratory centers ensure that we breathe in a manner that provides an adequate P_aO₂ and P_aCO₂ and acid–base status. On the other hand, we can volitionally increase or decrease our respiratory rate and tidal volume. To this point, we have discussed the sense of effort (mediated by corollary discharge) in the context of efferent neural output from the motor cortex, which implies a voluntary activity. Is there a similar sense of effort when the reflex components of the controller are stimulated, that is, when the efferent signals are originating in the medulla? An experiment to answer this question used a model in which subjects targeted their breathing to an elevated level of ventilation while their P_aCO₂ levels were altered¹⁶. This study is important because it is one of the first studies to show that the intensity of two types of respiratory discomfort may vary in opposite directions under the same experimental conditions. The study also provides additional information about the origins of the sense of effort. This finding helps build the case that qualitatively different respiratory sensations arise from different physiological mechanisms.

In this study¹⁶, subjects breathed at a constant level of ventilation while P_aCO₂ was kept at 40 mm Hg or surreptitiously raised to 50 mm Hg (the subjects and the researcher supervising the ratings were blinded to the level of carbon dioxide) by adding different amounts of CO₂ to the inspired gas. Subjects rated two sensations, “effort to breathe” and “breathing discomfort,” at two levels of ventilation, resting breathing and at an elevated level determined by a visual target. The goals of the study design were twofold. First, the investigators wished to look at sensations associated with two levels of motor output—normal ventilation and an elevated level of ventilation—under the condition that P_aCO₂ was 40 mm Hg. At a normal P_aCO₂, the neural output to the ventilatory muscles was presumably arising primarily from the motor cortex. One would predict that the sense of effort, which correlates with the neural output from the motor cortex, would increase when the subjects increased their level of ventilation. The results of the study bore out this prediction.

The second part of the protocol was designed to examine sensations associated with an elevated level of ventilation when P_aCO₂ was varied between 40 and 50 mm Hg. The investigators hypothesized that neural output to the ventilatory muscles from the brainstem that results from a reflex command, via stimulation of the chemoreceptors, does not generate the same sense of effort as output from the motor cortex associated with a voluntary command. If the hypothesis were true, you would predict that the sense of effort associated with a given level of ventilation would be less with an elevated P_aCO₂ than when one has to voluntarily work to generate the elevated level of ventilation. The results demonstrated that, at a P_aCO₂ of 50 mm Hg, the sense of effort was less than when the P_aCO₂ was 40 mm Hg. Thus, despite the fact that the output of the ventilatory pump was the same (i.e., ventilation was constant) under both conditions, the sense of effort was different. This is consistent with the hypothesis that ventilation that is stimulated by the chemoreceptors and originates in the brainstem does not generate the same corollary discharge to the sensory cortex as does voluntary hyperpnea. On the other hand, the sense of breathing discomfort (what other experiments have shown to be “air hunger” or “an increased urge to breathe”) increased as P_aCO₂ was increased, despite the fact that ventilation was held constant. Taken together, these findings suggest the dyspnea associated with acute hypercapnia, and presumed stimulation of the chemoreceptors, is physiologically distinct from the sense of effort.