{"doi":"10.1016/j.cub.2024.11.070","title":"Multiple mechanisms of action for an extremely painful venom","abstract":"Evolutionary arms races can lead to extremely specific and effective defense mechanisms, including venoms that deter predators by targeting nociceptive (pain-sensing) pathways. The venom of velvet ants (Hymenoptera: Mutillidae) is notoriously painful. It has been described as \"Explosive and long lasting, you sound insane as you scream. Hot oil from the deep fryer spilling over your entire hand.\" 1 The effectiveness of the velvet ant sting against potential predators has been shown across vertebrate orders, including mammals, amphibians, reptiles, and birds. 2 , 3 , 4 This leads to the hypothesis that velvet ant venom targets a conserved nociception mechanism, which we sought to uncover using Drosophila melanogaster as a model system. Drosophila larvae have peripheral sensory neurons that sense potentially damaging (noxious) stimuli such as high temperature, harsh mechanical touch, and noxious chemicals. 5 , 6 , 7 , 8 They share features with vertebrate nociceptors, including conserved sensory receptor channels. 9 , 10 We found that velvet ant venom strongly activated Drosophila nociceptors through heteromeric Pickpocket/Balboa (Ppk/Bba) ion channels, through a single venom peptide, Do6a. Drosophila Ppk/Bba is homologous to mammalian acid-sensing ion channels (ASICs). 11 However, Do6a did not produce behavioral signs of nociception in mice, which was instead triggered by other venom peptides that are non-specific and less potent on Drosophila nociceptors. This suggests that Do6a has an insect-specific function. In fact, we further demonstrated that the velvet ant's sting produced aversive behavior in a predatory praying mantis. Together, our results indicate that velvet ant venom acts through different molecular mechanisms in vertebrates and invertebrates.","journal":"Current Biology","year":2025,"id":530153,"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":5,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.9599,"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":1353198,"name":"Luana C. de Assis Ferreira","orcid":null,"position":1,"is_corresponding":false},{"id":348998,"name":"Jonathan C. Trinidad","orcid":"0000-0002-8279-1509","position":2,"is_corresponding":false},{"id":1353199,"name":"Sunčica Šašić","orcid":null,"position":3,"is_corresponding":false},{"id":314029,"name":"Andrea G. Hohmann","orcid":"0000-0003-0941-6435","position":4,"is_corresponding":false},{"id":424525,"name":"W. Daniel Tracey","orcid":"0000-0003-4666-8199","position":5,"is_corresponding":false},{"id":1329685,"name":"Lydia J. Borjon","orcid":"0000-0002-3680-4145","position":0,"is_corresponding":true}],"reference_count":61,"raw_metadata":null,"created_at":"2026-07-19T02:51:01.235017Z","pmid":"39765227","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":[]}