title: Nocistatin sensitizes TRPA1 channels in peripheral sensory neurons.
abstract: The ability of sensory neurons to detect potentially harmful stimuli relies on specialized molecular signal detectors such as transient receptor potential (TRP) A1 ion channels. TRPA1 is critically implicated in vertebrate nociception and different pain states. Furthermore, TRPA1 channels are subject to extensive modulation and regulation - processes which consequently affect nociceptive signaling. Here we show that the neuropeptide Nocistatin sensitizes TRPA1-dependent calcium influx upon application of the TRPA1 agonist mustard oil (MO) in cultured sensory neurons of dorsal root ganglia (DRG). Interestingly, TRPV1-mediated cellular calcium responses are unaffected by Nocistatin. Furthermore, Nocistatin-induced TRPA1-sensitization is likely independent of the Nocistatin binding partner 4-Nitrophenylphosphatase domain and non-neuronal SNAP25-like protein homolog 1 (NIPSNAP1) as assessed by siRNA-mediated knockdown in DRG cultures. In conclusion, we uncovered the sensitization of TRPA1 by Nocistatin, which may represent a novel mechanism how Nocistatin can modulate pain.
authors.affiliation: a Max Planck Institute of Experimental Medicine, Somatosensory Signaling and Systems Biology Group , Goettingen , Germany.
authors.forename: Luca
authors.initials: L
authors.lastname: Avenali
authors.affiliation: a Max Planck Institute of Experimental Medicine, Somatosensory Signaling and Systems Biology Group , Goettingen , Germany.
authors.forename: Oli
authors.initials: O
authors.lastname: Abate Fulas
authors.affiliation: a Max Planck Institute of Experimental Medicine, Somatosensory Signaling and Systems Biology Group , Goettingen , Germany.
authors.forename: Julia
authors.initials: J
authors.lastname: Sondermann
authors.affiliation: a Max Planck Institute of Experimental Medicine, Somatosensory Signaling and Systems Biology Group , Goettingen , Germany.
authors.forename: Pratibha
authors.initials: P
authors.lastname: Narayanan
authors.affiliation: a Max Planck Institute of Experimental Medicine, Somatosensory Signaling and Systems Biology Group , Goettingen , Germany.
authors.forename: David
authors.initials: D
authors.lastname: Gomez-Varela
authors.affiliation: a Max Planck Institute of Experimental Medicine, Somatosensory Signaling and Systems Biology Group , Goettingen , Germany.
authors.forename: Manuela
authors.initials: M
authors.lastname: Schmidt
mesh_terms: D000701:Analgesics, Opioid / Q000494:pharmacology*; D000818:Animals; D002118:Calcium / Q000502:physiology; D005727:Ganglia, Spinal / Q000187:drug effects* / Q000502:physiology; D008810:Mice, Inbred C57BL; D018847:Opioid Peptides / Q000494:pharmacology*; D011984:Sensory Receptor Cells / Q000187:drug effects* / Q000502:physiology; D000074025:TRPA1 Cation Channel; D050051:Transient Receptor Potential Channels / Q000502:physiology*
chemical_list: D000701:Analgesics, Opioid; D018847:Opioid Peptides; D000074025:TRPA1 Cation Channel; D050051:Transient Receptor Potential Channels; C475685:Trpa1 protein, mouse; C111148:nocistatin; D002118:Calcium
keywords: NIPSNAP1; Nocistatin; TRPA1; nociception; peripheral sensory neurons; sensitization