10.1371/journal.pone.0151386 Valentina Malafoglia Valentina Malafoglia Lorenzo Traversetti Lorenzo Traversetti Floriano Del Grosso Floriano Del Grosso Massimiliano Scalici Massimiliano Scalici Filomena Lauro Filomena Lauro Valeria Russo Valeria Russo Tiziana Persichini Tiziana Persichini Daniela Salvemini Daniela Salvemini Vincenzo Mollace Vincenzo Mollace Massimo Fini Massimo Fini William Raffaeli William Raffaeli Carolina Muscoli Carolina Muscoli Marco Colasanti Marco Colasanti Transient Receptor Potential Melastatin-3 (TRPM3) Mediates Nociceptive-Like Responses in <i>Hydra vulgaris</i> Public Library of Science 2016 HSP heat shock Transient Receptor mammal nitric oxide synthase heat shock protein 70 NOS transcription erythroid 2- coelenterate Hydra vulgaris TRPM 3 antagonist TRPM 3 agonist SOD nociceptor calcium channel 2016-03-14 00:53:44 Dataset https://plos.figshare.com/articles/dataset/Transient_Receptor_Potential_Melastatin-3_TRPM3_Mediates_Nociceptive-Like_Responses_in_i_Hydra_vulgaris_i_/3964680 <div><p>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 <i>Hydra vulgaris</i>, the most primitive organism possessing a nervous system. In particular, we found that <i>H</i>. <i>vulgaris</i> 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>i</i>.<i>e</i>., pregnenolone sulfate) induce the modulation of the heat shock protein 70 (HSP70<i>)</i> 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>i</i>.<i>e</i>., 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.</p></div>