Are juxtacapillary (J) receptors responsible for cough?

J Receptors and Cough: No Direct Role

J receptors (juxtacapillary receptors) do not initiate cough; cough reflexes are mediated by specialized myelinated cough receptors and airway C-fibers, not by J receptors. 1, 2

What J Receptors Actually Do

J receptors are unmyelinated vagal afferent nerve endings located in the pulmonary interstitial tissue immediately adjacent to pulmonary capillaries 2. Their primary function is fundamentally different from cough generation:

Primary Reflex Response

• J receptors produce rapid, shallow breathing (tachypnea with reduced tidal volume) when activated, not cough 2
• This breathing pattern contributes to dyspnea in pulmonary congestion and heart failure 2
• They are quiescent during normal tidal breathing and relatively unresponsive to lung inflation 2, 3

Activation Triggers

• Increased pulmonary capillary pressure leading to elevated interstitial pressure or volume 2, 4
• Pulmonary vascular congestion (e.g., pulmonary embolism, heart failure) 2
• Pulmonary edema 4, 5
• They have slow conduction velocities (0.8-1.5 m/s) characteristic of unmyelinated C-fibers 3, 6

The Actual Cough Receptors

Widdicombe Cough Receptors (Primary)

Cough is primarily mediated by myelinated, mechanically sensitive, capsaicin-insensitive vagal afferent nerves called "cough receptors" 1:

• Fast conduction velocity (~5 m/s), much faster than J receptors 1
• Located exclusively in extrapulmonary airways (larynx, trachea, mainstem bronchi) 1
• Activated by mechanical stimulation and protons 1
• Insensitive to capsaicin, unlike C-fibers 1
• Use glutamate as their primary neurotransmitter 1

Airway C-Fibers (Secondary)

Bronchopulmonary C-fibers also contribute to cough but through different mechanisms 1:

• Activated by capsaicin, bradykinin, TRPA1 activators, and protons 1
• Coughing evoked by these stimuli is prevented by capsaicin desensitization 1
• Express neuropeptides like substance P (in animals) 1
• Slow conduction velocity (<1 m/s) 1

Key Distinctions from Other Receptors

J Receptors vs. Rapidly Adapting Receptors (RARs)

• RARs have much faster conduction (14-23 m/s) and are myelinated 3
• RARs mediate bronchospasm and mucus secretion, not the rapid shallow breathing of J receptors 3
• RARs respond to lung inflation; J receptors do not 3

Why J Receptors Don't Cause Cough

There is accumulating evidence that C-fiber receptors (including J receptors) may actually cause apnea and rapid shallow breathing, and reflexly inhibit cough rather than cause it 7:

• J receptors may indirectly enhance cough only through secondary mechanisms 7
• When C-fiber receptors release tachykinins, these can cause plasma extravasation, which increases interstitial fluid volume 7
• This increased fluid volume can then activate RARs (rapidly adapting receptors), which may indirectly trigger cough 7

Clinical Implications

Management Focus

• There is no direct clinical management of J receptors themselves; treatment targets underlying conditions like heart failure and pulmonary edema 2
• Therapeutic reduction of pulmonary capillary pressure (diuretics, vasodilators, afterload reduction) diminishes J-receptor stimulation 2

Common Pitfall

Do not attribute cough to J-receptor activation—this is a fundamental misunderstanding of respiratory neurophysiology 1, 2. If a patient with pulmonary congestion is coughing, the cough is mediated by cough receptors or airway C-fibers responding to airway irritation, mucus, or inflammation, not by J receptors responding to interstitial congestion.

Ventilator Management

• Avoid excessive positive end-expiratory pressure (PEEP) in patients with left-ventricular dysfunction, as high PEEP raises pulmonary capillary pressure and further stimulates J receptors 2