Upstream eventOpening of calcium channel, Calcium influx
SP (Substance P) release, Local increase of SP
Key Event Relationship Overview
AOPs Referencing Relationship
Life Stage Applicability
Key Event Relationship Description
Activation of TRPA1 or TRPV1 channels in nociceptive neurons produces calcium transients which signal the neuron to release substance P, among other neuropeptides. The local effects of substance P release are collectively termed neurogenic inflammation.
Evidence Supporting this KER
It is unknown how TRP-mediated calcium transients directly lead to substance P release but it does not conflict with known biology.
Nociceptive neurons have been repeatedly shown to induce neurogenic inflammation in tissue by releasing substance P and other neuropeptides (Purkiss et al, 2002, Tang et al, 2008, Nakamura et al, 2012).
Uncertainties and Inconsistencies
Mechanism is not known.
Quantitative Understanding of the Linkage
Substance P release from neurons following TRPA1 or TRPV1 agonists are typically demonstrated to be dose-responsive. The sensitivity of TRP channels may be modulated by cell signaling and events mediated by calcium transients may be modulated by cell signaling events which impact signaling through G-protein, PKC, or inositol triphosphate pathways.