title: Monoamines and neuropeptides interact to inhibit aversive behaviour in Caenorhabditis elegans.
abstract: Pain modulation is complex, but noradrenergic signalling promotes anti-nociception, with α(2)-adrenergic agonists used clinically. To better understand the noradrenergic/peptidergic modulation of nociception, we examined the octopaminergic inhibition of aversive behaviour initiated by the Caenorhabditis elegans nociceptive ASH sensory neurons. Octopamine (OA), the invertebrate counterpart of norepinephrine, modulates sensory-mediated reversal through three α-adrenergic-like OA receptors. OCTR-1 and SER-3 antagonistically modulate ASH signalling directly, with OCTR-1 signalling mediated by Gα(o). In contrast, SER-6 inhibits aversive responses by stimulating the release of an array of 'inhibitory' neuropeptides that activate receptors on sensory neurons mediating attraction or repulsion, suggesting that peptidergic signalling may integrate multiple sensory inputs to modulate locomotory transitions. These studies highlight the complexity of octopaminergic/peptidergic interactions, the role of OA in activating global peptidergic signalling cascades and the similarities of this modulatory network to the noradrenergic inhibition of nociception in mammals, where norepinephrine suppresses chronic pain through inhibitory α(2)-adrenoreceptors on afferent nociceptors and stimulatory α(1)-receptors on inhibitory peptidergic interneurons.
authors: Department of Biological Sciences, University of Toledo, Toledo, OH 43606, USA.
authors: Holly
authors: H
authors: Mills
authors: Rachel
authors: R
authors: Wragg
authors: Vera
authors: V
authors: Hapiak
authors: Michelle
authors: M
authors: Castelletto
authors: Jeffrey
authors: J
authors: Zahratka
authors: Gareth
authors: G
authors: Harris
authors: Philip
authors: P
authors: Summers
authors: Amanda
authors: A
authors: Korchnak
authors: Wenjing
authors: W
authors: Law
authors: Bruce
authors: B
authors: Bamber
authors: Richard
authors: R
authors: Komuniecki
mesh_terms: D020003:1-Octanol / Q000494:pharmacology; D000818:Animals; D030801:Animals, Genetically Modified; D001362:Avoidance Learning; D015306:Biogenic Monoamines / Q000378:metabolism*; D017173:Caenorhabditis elegans / Q000502:physiology*; D019204:GTP-Binding Proteins / Q000378:metabolism; D009479:Neuropeptides / Q000378:metabolism*; D016133:Polymerase Chain Reaction; D012701:Serotonin / Q000494:pharmacology; D015398:Signal Transduction; D014982:Xenopus laevis
chemical_list: D015306:Biogenic Monoamines; D009479:Neuropeptides; D012701:Serotonin; D019204:GTP-Binding Proteins; D020003:1-Octanol