Type III/IV Muscle Afferents in Airway and Thermoregulatory Responses

Group III/IV afferents are nerves that relay information from the muscles to the central nervous system. This afferent activity acts as negative feedback to minimize the overall strain placed on muscles . Without this negative feedback, locomotor muscles become damaged during intense exercise. It is well-established that group III/IV afferents are required for normal breathing and blood pressure responses to physical activity. In certain disease states, such as chronic obstructive pulmonary disease, heart failure and hypertension, group III/IV afferents become dysfunctional and lead to exercise intolerance. This is a major issue in these patient groups where regular exercise is advocated to slow or halt disease progression. Understanding how these reflexes contribute to basic cardiorespiratory responses to exercise is thus warranted.

At the onset of exercise, there is a near instantaneous decrease in airway resistance that permits high rates of breathing ; these high rates of breathing are essential to ensure appropriate oxygen transport to working muscles. The decrease in airway resistance is facilitated by a rapid withdrawal of parasympathetic tone to the smooth muscle lining the airways, allowing them to open up and remain rigid. Evidence in cats and dogs indicate that group III/IV afferents reflexively contribute to this response, thereby coupling airway dilation to muscle work. Airway resistance can be quantified by measuring the work required by breathing muscles to pull air into and push air out of the lungs. If the magnitude of airway dilation changes due to the suppression of group III/IV afferents, the investigators would observe a compensatory increase in how much work is required to overcome resistance. This has not been investigated directly in humans.

Alongside the fundamental cardiorespiratory responses to exercise, humans mount powerful thermoregulatory responses that dissipate heat generated from muscle work. The primary thermoregulatory responses in humans are eccrine sweating and skin vasodilation; both of which are activated as body temperature rises. Exercise augments thermoregulatory responses to heating, and sweating is initiated within 1-2 seconds of initiating exercise despite body temperature remaining stable. Thus, there is clearly a link between muscular work and thermoregulation. Reduced preparations in cats have shown that group III/IV afferent activity is elevated during external muscle heating, and human sweating responses are more closely coupled to muscle temperature than to core or skin temperature. To date, no study in humans has tried to isolate the role of group III/IV afferents on thermoregulatory responses to exercise.

These group III/IV afferents can be studied in exercising humans by suppressing their activity using intrathecal (spinal) opioids. Simply, a subject exercises on two different occasions, one with intact muscle reflex feedback, and the other with the feedback suppressed; differences in exercise responses are isolated to the role of group III/IV afferents. The investigators aim to use this model to quantify the contribution of group III/IV afferent reflexes to airway resistance, sweating and skin vasodilation.