Obligatory neural feedback control of exercise cardiorespiratory function and performance

Q: What is the clinical evidence from this study?

Study design: Review. Population: Healthy individuals, Chronic Heart Failure (CHF), COPD, and Hypertension. Intervention: Neural sensory feedback (muscle afferents, lung stretch receptors, carotid chemoreceptors).

Q: What does this research mean for the field?

Neural sensory feedback mechanisms are obligatory for cardiorespiratory function during exercise and show enhanced contributions in chronic diseases such as heart failure and COPD. Novelty: ClaimNovelty.SYNTHESIS. Consensus alignment: ConsensusAlignment.NEUTRAL.

Jerome A. Dempsey; Barbara J. Morgan

doi:10.1152/japplphysiol.00709.2025

November 3, 2025Journal of Applied PhysiologyOpen Access

Obligatory neural feedback control of exercise cardiorespiratory function and performance

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Key result

Peripheral sensory feedback is essential for exercise cardiorespiratory function and becomes hypersensitive in disease.

Why the study?

To review the contributions of four sources of neural sensory feedback to cardiorespiratory responses and exercise limitation in health and disease.

Key Points

To review the obligatory roles of four distinct neural sensory feedback pathways in regulating cardiorespiratory responses, muscle fatigue, and performance during exercise in health and chronic disease.
Synthesized experimental findings from healthy humans and animal models using selective pharmacological or mechanical blockades of sensory feedback pathways during physiologic exercise.
Evaluated interventions targeting group III and IV muscle afferents, respiratory muscle loading/unloading, vagal lung afferents, and carotid chemoreceptor inputs.
Selective blockade of sensory inputs from locomotor muscles, respiratory muscles, carotid chemoreceptors, or vagal lung afferents significantly impairs cardiorespiratory regulation, alters locomotor effort, and exacerbates fatigue.
In chronic conditions including chronic heart failure, chronic obstructive pulmonary disease, and hypertension, these sensory feedback mechanisms display hypersensitivity and elevated tonic activity even during mild exercise.
Intrathecal lumbar fentanyl administration blocks approximately 40% to 50% of group III and IV muscle afferents in humans without impairing efferent motor drive, confirming their regulatory role.

Structured PICO

P

Population

Healthy humans, patients with chronic diseases (chronic heart failure, chronic obstructive pulmonary disease, hypertension), and experimental animals

E

Exposure

Blockade or partial blockade of sensory feedback mechanisms (e.g., intrathecal fentanyl for muscle afferents, transient hyperoxia for carotid chemoreceptors, mechanical ventilation for inspiratory muscle unloading)

C

Comparator

Intact (unblocked) physiological exercise conditions

O

Outcome

Cardiorespiratory function, locomotor effort, muscle fatigue, and exercise performance

Sensory feedback from muscles, lungs, and chemoreceptors is obligatory for regulating physiological cardiorespiratory responses, preventing excessive muscle fatigue, and pacing effort during exercise.

Limitations

Fentanyl blockade of locomotor muscle afferents is only a partial block, rendering it unable to quantify the full contribution of muscle afferents.
Inspiratory muscle unloading via positive pressure mechanical ventilation increases pulmonary vascular resistance and reduces the mechanical effects of the respiratory muscle pump on venous return.
Prolonged hyperoxia (>2 minutes) is not a specific indicator of carotid chemoreflex inhibition because it stimulates, rather than inhibits, sympathetic outflow and ventilation.
Intrathecal fentanyl blockade provides only a partial block, limiting quantification of the full contribution of muscle afferents.
Responses to prolonged hyperoxia are not specific indicators of carotid chemoreflex inhibition.
Inspiratory muscle unloading via positive pressure mechanical ventilation increases pulmonary vascular resistance and attenuates venous return.

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Implication

Sensory afferent hypersensitivity may contribute to exercise intolerance in HF, COPD, and hypertension; leaves open whether targeted blockade improves outcomes.

Abstract

Our review addresses the contributions of four sources of neural sensory feedback, namely, locomotor and respiratory muscle afferents, lung stretch receptors, and carotid chemoreceptors, to the cardiorespiratory responses to rhythmic exercise and to exercise limitation in health and disease. Experiments in healthy humans and animals that used a blockade or partial blockade of each feedback mechanism during physiological exercise demonstrated the obligatory nature of each of these sensory inputs to cardiorespiratory function, locomotor effort and muscle fatigue, and exercise performance. More recent research has revealed enhanced contributions of these feedback influences to exercise cardiorespiratory function in chronic heart failure, chronic obstructive pulmonary disease, and hypertension. Future research needs to address: 1) how these obligatory neural feedback mechanisms might interact with a raised respiratory CO 2 exchange in regulating the hyperpnea of exercise; and 2) the pathogenesis of feedback hypersensitivity in chronic diseases and the means and therapeutic benefits of its normalization.

Discussion

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Cite This Study

Dempsey et al. (2025) conducted a review in Healthy individuals, Chronic Heart Failure (CHF), COPD, and Hypertension. Neural sensory feedback (muscle afferents, lung stretch receptors, carotid chemoreceptors) was evaluated. Neural sensory feedback from locomotor and respiratory muscles, lung stretch receptors, and carotid chemoreceptors is obligatory for exercise cardiorespiratory function and is hypersensitive in disease.

synapsesocial.com/papers/6a1f00f7d6e47ed9f1e6aed0 https://doi.org/10.1152/japplphysiol.00709.2025

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Obligatory neural feedback control of exercise cardiorespiratory function and performance

Key Points

Structured PICO

Limitations

Ask about this paper

Implication

Abstract

Discussion

Cite This Study

Obligatory neural feedback control of exercise cardiorespiratory function and performance

Key Points

Structured PICO

Limitations

Ask about this paper

Implication

Abstract

Discussion

Cite This Study

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