Nematocyte discharge of is the most relevant aspect of Cnidarian physiology. The nematocyte is a specialized cell, localized in tentacles, oral arms and acontia, producing an organoid, termed nematocyst, with a capsule wall, containing the capsule fluid and an inverted tubule. Nematocyte discharge, triggered to perform both defence and predation strategies, occurs under a chemico-physical stimulation and consists in the rapid eversion of the tubule and toxins delivery. A possible neural pathway involved in discharge is here investigated through a physiological approach, with the aim of verifying the role of neurotransmitters in oral arms of the Scyphozoa Pelagia noctiluca, collected in the Strait of Messina (Italy). Excised oral arms were submitted to a combined chemico-physical stimulation by treatment with compounds already known to inducing discharge as 5-HT, carbachol, artherenol, glycine, glutamate and arginin (10^­3M, 10^­6M or, alternatively, 10^­8M) in ASW Ca²⁺ 10 mM. Such treatment was followed by mechanical stimulation by a non-vibrating test probe. Oral arms, treated with each of these compounds, exhibited a discharge significantly higher than the control, showing a chemosensitizing mechanism with a dose-dependent effect. Mechanical stimulation, not associated to a chemical stimulation, was not sufficient to trigger discharge. These findings show that, similarly to what observed on other Cnidaria specimens, substances considered as neuropeptides and neurotransmitters may be present in Pelagia noctiluca oral arms and are involved in discharge activation.