title: Transient Receptor Potential Melastatin-3 (TRPM3) Mediates Nociceptive-Like Responses in Hydra vulgaris.
abstract: The ability of mammals to feel noxious stimuli lies in a heterogeneous group of primary somatosensory neurons termed nociceptors, which express specific membrane receptors, such as the Transient Receptor Potential (TRP) family. Here, we show that one of the most important nociceptive-like pathways is conserved in the freshwater coelenterate Hydra vulgaris, the most primitive organism possessing a nervous system. In particular, we found that H. vulgaris expresses TRPM3, a nociceptor calcium channel involved in the detection of noxious heat in mammals. Furthermore, we detected that both heat shock and TRPM3 specific agonist (i.e., pregnenolone sulfate) induce the modulation of the heat shock protein 70 (HSP70) and the nitric oxide synthase (NOS), two genes activated by TRP-mediated heat painful stimuli in mammals. As expected, these effects are inhibited by a TRPM3 antagonist (i.e., mefenamic acid). Interestingly, the TRPM3 agonist and heat shock also induce the expression of nuclear transcription erythroid 2-related factor (Nrf2) and superoxide dismutase (SOD), known markers of oxidative stress; noteworthy gene expression was also inhibited by the TRPM3 antagonist. As a whole, our results demonstrate the presence of conserved molecular oxidative/nociceptive-like pathways at the primordial level of the animal kingdom.
authors.affiliation: Department of Science, University of Roma Tre, Rome, Italy.|Institute for Research on Pain, ISAL-Foundation, Torre Pedrera (RN), Italy.|IRCCS San Raffaele Pisana, Rome, Italy.
authors.forename: Valentina
authors.initials: V
authors.lastname: Malafoglia
authors.affiliation: Department of Science, University of Roma Tre, Rome, Italy.
authors.forename: Lorenzo
authors.initials: L
authors.lastname: Traversetti
authors.affiliation: Department of Science, University of Roma Tre, Rome, Italy.
authors.forename: Floriano
authors.initials: F
authors.lastname: Del Grosso
authors.affiliation: Department of Science, University of Roma Tre, Rome, Italy.
authors.forename: Massimiliano
authors.initials: M
authors.lastname: Scalici
authors.affiliation: IRCCS San Raffaele Pisana, Rome, Italy.
authors.forename: Filomena
authors.initials: F
authors.lastname: Lauro
authors.affiliation: Department of Science, University of Roma Tre, Rome, Italy.
authors.forename: Valeria
authors.initials: V
authors.lastname: Russo
authors.affiliation: Department of Science, University of Roma Tre, Rome, Italy.
authors.forename: Tiziana
authors.initials: T
authors.lastname: Persichini
authors.affiliation: Department of Pharmacological and Physiological Science, Saint Louis University School of Medicine, St Louis, United States of America.
authors.forename: Daniela
authors.initials: D
authors.lastname: Salvemini
authors.affiliation: IRC-FSH, Department of Health Science, University of 'Magna Graecia', Catanzaro, Italy.
authors.forename: Vincenzo
authors.initials: V
authors.lastname: Mollace
authors.affiliation: IRCCS San Raffaele Pisana, Rome, Italy.
authors.forename: Massimo
authors.initials: M
authors.lastname: Fini
authors.affiliation: Institute for Research on Pain, ISAL-Foundation, Torre Pedrera (RN), Italy.
authors.forename: William
authors.initials: W
authors.lastname: Raffaeli
authors.affiliation: IRC-FSH, Department of Health Science, University of 'Magna Graecia', Catanzaro, Italy.
authors.forename: Carolina
authors.initials: C
authors.lastname: Muscoli
authors.affiliation: Department of Science, University of Roma Tre, Rome, Italy.
authors.forename: Marco
authors.initials: M
authors.lastname: Colasanti
mesh_terms: D000818:Animals; D005786:Gene Expression Regulation / Q000187:drug effects; D018840:HSP70 Heat-Shock Proteins / Q000235:genetics / Q000378:metabolism; D018869:Heat-Shock Response / Q000187:drug effects / Q000235:genetics; D006829:Hydra / Q000187:drug effects / Q000235:genetics / Q000378:metabolism*; D059225:Nociception / Q000187:drug effects; D011284:Pregnenolone / Q000494:pharmacology; D021381:Protein Transport / Q000187:drug effects; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D013482:Superoxide Dismutase / Q000235:genetics / Q000378:metabolism; D050053:TRPM Cation Channels / Q000235:genetics / Q000378:metabolism*
chemical_list: D018840:HSP70 Heat-Shock Proteins; D012333:RNA, Messenger; D050053:TRPM Cation Channels; C018370:pregnenolone sulfate; D011284:Pregnenolone; D013482:Superoxide Dismutase