TRPV1 Sensory Nerves May Be Key to the Genesis of Airway Hyperreactivity in Experimental Asthma

TRPV1 Sensory Nerves May Be Key to the Genesis of Airway Hyperreactivity in Experimental Asthma

A new study in the Proceedings of the National Academy of Sciences (PNAS) of the USA implicates the transient receptor potential vanilloid 1 (TRPV1)-expressing sensory nerves in the pathogenesis of asthma and/or asthma attacks.

The TRPV1 receptor, initially identified as the receptor for capsaicin, the hot component of chilli peppers, is typically expressed in sensory neurons and responds to various stimuli including noxious heat, protons and tissue acidosis.

Vagal sensory neurons innervate the entire respiratory tract and affect cellular networks through axonal and local reflexes, but also signal the brain to regulate pulmonary functions.Interestingly, recent evidence indicates that TRPV1 sensory nerves trigger IL-23 output in psoriasis, whereas the TRPV1 receptor is functionally expressed in T cells.

In the PNAS study Dimitri Tränkner and a joint research team from the Janelia Farm Research Campus, Ashburn, VA; the NationalInstitutes of Health, Bethesda, MD and the Columbia University, NY, have used the ovalbumin-sensitized murine model of asthma to investigate the role of sensory innervation in airway hyperresponsiveness.

The researchers found that in this disease modelablating or geneticallysilencing TRPV1 vagal sensory nerves prevented the airway hyperreactivityand bronchoconstriction, in spite of the presence of a full-fledgedlung inflammatory response. Conversely, they observed that pharmacological stimulation of the receptor forsphingosine-1-phosphate (S1PR3),which is restricted to TRPV1 neurons, resulted in a robustairway hyperreactivity in the absence of immune sensitizationwith ovalbumin.

The authors suggest that during allergic inflammationthe release of proinflammatory mediatorsare able to sensitize vagal sensory nerves, which, in turn, modulate airway responses to broncho-constrictingstimuli and further increase the severity of airway hyperreactivity.

These observations seem to substantiate another recent study (Kristof Raemdonck et al., Thorax 2012;67:19) indicating that during the late asthmaticresponse,theallergen challenge leadsto sensory nerve activation, which initiates a reflex event leading toa parasympathetic cholinergic constrictor response.

Source: Proc Natl Acad Sci U S A, 2014, 111:11515. doi: 10.1073/pnas.1411032111. Epub 2014 Jul 21
Read more: pnas.org




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