Stimulation of TRPV1+ peripheral somatosensory nerves suppress inflammation via the somato-autonomic reflex

Excessive inflammation causes a wide range of diseases. Here, we found that stimulating TRPV1+ nerves at the nape activated the nucleus of the solitary tract and C1 neurons in the brainstem via the somatosensory afferent pathway, and rapidly induced the secretion of corticosterone, and drove the vagal-adrenal axis to release serum catecholamines, and activated the autonomic-splenic reflex to suppress cytokine production. RNA sequencing (RNA-seq) analysis revealed that stimulating TRPV1+ nerves significantly changed the expression of genes enriched in multiple pathways related to the inflammatory response in the spleen under pathological and normal physiological conditions. TRPV1 agonist lost these anti-inflammatory effects in trpv1ko mice. Our study revealed a neural circuit that stimulating TRPV1+ somatosensory afferents at the nape could concurrently drive the sympathetic and parasympathetic efferents to synergistically induce anti-inflammatory effects. Furthermore, stimulation of TRPV1+ peripheral sensory afferents in specific body regions is an efficient therapeutic approach to treat inflammatory diseases.