{"doi":"10.1113/jp290195","title":"Canoe full of hot paddlers: TRPV1 neurons steering cardiorespiratory control","abstract":"Asthma and chronic obstructive pulmonary disease (COPD) are conventionally described as inflammatory disorders, but inflammation alone does not explain all symptoms. Both are characterised by cough, dyspnoea, bronchoconstriction and systemic consequences arising from a combination of inflammation and exaggerated neural reflexes. The lung is rich in TRPV1-expressing vagal C-fibre nociceptors that sense heat and inflammation and trigger reflexes altering breathing, airway tone and cardiovascular function. In health they help steer the cardiorespiratory system smoothly and prevent damage. In asthma and COPD, the excitability of these fibres increases, and protective reflexes become pathological. In this sense the cardiorespiratory canoe is pulled off course, oversteered by neural pathways that normally stabilise function. TRPV1+ vagal C-fibres also shape host defence: in lung infection they suppress early neutrophil influx (Baral et al., 2018) yet promote antibody-mediated (humoral) immunity via vasoactive intestinal peptide (VIP) (Aguilar et al., 2024). In an allergic asthma mouse model, the same pathway enhances Type 2 immunity via substance P, worsening disease (Aguilar et al., 2024). Nociceptors likewise shape fibrotic lung disease. In a bleomycin model, pharmacological ablation or genetic deletion of these neurons exacerbated pulmonary fibrosis by permitting maladaptive macrophage–neutrophil interactions (Hiroki et al., 2025). Here, nociceptors acted protectively, constraining inflammation and tissue remodelling. Thus, nociceptor influence is context dependent: destabilising in asthma and COPD, stabilising in fibrosis and time-dependent in infection. In most mammals, bronchial C-fibres monitor the conducting airways, whereas pulmonary C-fibres terminate in the parenchyma and include juxtacapillary (J) receptors. Bronchial C-fibres are neural crest-derived, with cell bodies in the jugular ganglia and projections to the paratrigeminal nucleus (Pa5). Their terminals lie in large conducting airways where they detect inhaled irritants and inflammatory mediators. When activated, they release substance P (Tac1) and neurokinin A, which promote bronchoconstriction, and calcitonin gene-related peptide (CGRP), which promotes vasodilatation and vascular leak; all three neuropeptides support immune-cell recruitment. Through Pa5 projections, bronchial fibres also initiate cough and parasympathetic reflexes that produce widespread bronchoconstriction and mucus secretion. Pulmonary C-fibres, in contrast, are placode-derived with cell bodies in the nodose ganglia and projections to the nucleus of the solitary tract (NTS). Their terminals lie in alveolar walls near pulmonary capillaries, where they detect ATP, adenosine and serotonin. Activation triggers the pulmonary chemoreflex, producing rapid shallow breathing, bradypnoea or apnoea, bradycardia and hypotension. These reflexes may protect the alveolar–capillary barrier, but in asthma sensitised pulmonary C-fibres exaggerate dyspnoea, worsen hypoxaemia and destabilise cardiovascular rhythms. Both bronchial and pulmonary C-fibres contribute to neurogenic inflammation, but their roles differ by location. Bronchial C-fibres, with terminals in the conducting airways, probably dominate bronchoconstriction and mucus secretion. Pulmonary C-fibres, situated near the pulmonary circulation, are well placed to promote vasodilatation, vascular leak and immune recruitment – the hallmarks of parenchymal neurogenic inflammation. Together these pathways converge to amplify airway instability during asthma exacerbations. If bronchial C-fibres provide the power strokes, pulmonary C-fibres provide the steering strokes, and when overapplied they too can send the canoe off course. In mice, the function and anatomical demarcation of jugular (nominally bronchial) and nodose (nominally pulmonary/J-receptor) C-fibres is less clear (Kollarik and Undem, 2004). In this issue of The Journal of Physiology, Patil et al. ","journal":"The Journal of Physiology","year":2025,"id":579548,"datarank":0.0,"base_score":0.0,"endowment":0.0,"self_citation_contribution":0.0,"citation_network_contribution":0.0,"self_endowment_contribution":0.0,"citer_contribution":0.0,"corpus_percentile":null,"corpus_rank":null,"citation_count":0,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.9619,"is_data_producer":false,"deposit_databanks":null,"is_oa":true,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":"2025-01-01","fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":674328,"name":"Nicholas Jendzjowsky","orcid":"0000-0002-4342-1839","position":1,"is_corresponding":false},{"id":864225,"name":"Richard J. A. Wilson","orcid":"0000-0001-9942-4775","position":0,"is_corresponding":true}],"reference_count":6,"raw_metadata":null,"created_at":"2026-07-19T02:58:30.282164Z","pmid":"41166350","pmcid":null,"fwci":null,"citation_percentile":null,"influential_citations":0,"oa_status":null,"license":null,"views":0,"total_file_size_bytes":0,"version_count":0,"fair_f":null,"fair_a":null,"fair_i":null,"fair_r":null,"fair_zscore":null,"fair_rationale":null,"fair_model":null,"fair_agent_version":null,"fair_fulltext_source":null,"fair_has_llm":null,"fair_computed_at":null,"clinical_trials":[],"software_tools":[],"db_accessions":[],"linked_datasets":[],"topics":[]}