Gαq and Phospholipase Cβ signaling regulate nociceptor sensitivity in Drosophila melanogaster larvae

Abstract

Drosophila melanogaster larvae detect noxious thermal and mechanical stimuli in their environment using polymodal nociceptor neurons whose dendrites tile the larval body wall. Activation of these nociceptors by potentially tissue-damaging stimuli elicits a stereotyped escape locomotion response. The cellular and molecular mechanisms that regulate nociceptor function are increasingly well understood, but gaps remain in our knowledge of the broad mechanisms that control nociceptor sensitivity. In this study, we use cell-specific knockdown and overexpression to show that nociceptor sensitivity to noxious thermal and mechanical stimuli is correlated with levels of Gαq and phospholipase Cβ signaling. Genetic manipulation of these signaling mechanisms does not result in changes in nociceptor morphology, suggesting that changes in nociceptor function do not arise from changes in nociceptor development, but instead from changes in nociceptor activity. These results demonstrate roles for Gαq and phospholipase Cβ signaling in facilitating the basal sensitivity of the larval nociceptors to noxious thermal and mechanical stimuli and suggest future studies to investigate how these signaling mechanisms may participate in neuromodulation of sensory function.

Antinociceptive modulation by the adhesion GPCR CIRL promotes mechanosensory signal discrimination

“…Despite their important roles in health and disease, an understanding of how these mechanistically different transduction processes are carried out at the molecular level is only just beginning to emerge ( Delmas et al, 2011 ; Julius, 2013 ; Murthy et al, 2017 ; Szczot et al, 2017 ; Zhang et al, 2019 ). Similar to mammalian DRG neurons, Drosophila nociceptors are modulated by GPCRs ( Hu et al, 2017 ; Kaneko et al, 2017 ; Herman et al, 2018 ) and can be negatively regulated by G i/o signalling ( Christianson et al, 2016 ; Honjo et al, 2016 ). In the present study, we provide evidence that CIRL, an evolutionarily conserved aGPCR, reduces nociceptor responses to mechanical insult in Drosophila larvae.…”

Identification of a Pain-Specific Gene Expression Profile for Pediatric Recurrent Abdominal Pain

“…PGE 2 is typically expressed in low levels that can be increased in response to inflammation (43). In the context of pain, PGE 2 can directly activate E prostanoid (EP) receptors, a family of G protein coupled receptors, to stimulate an increase in intracellular calcium levels through G protein signaling (42)(43)(44)(45). This calcium influx in sensory neurons promotes neurotransmitter release into synaptic junctions, ultimately increasing neuronal communication and perception of pain.…”

Local and generalized sensitization of thermally evoked defensive behavior in caterpillars

“…The induction of peripheral sensitization in Drosophila has been shown to depend on many signaling pathways involved in tissue damage and repair including tachykinins (Im et al, ), TNF and Hh (Babcock et al, ), as well as other cytokines (Follansbee et al, ), insulin (Im et al, ), dual oxidase enzymes (Jang et al, ), and reactive oxygen species (Arenas et al, ). Most of the evidence suggests that the Class IV multi‐dendritic neurons increase the sensitivity to thermal and mechanical stimuli through specific regulatory pathways rather than from neuronal damage (Herman, Willits, & Bellemer, ). In addition to these mechanisms, it is possible that some thermoreceptor proteins are directly modified by strong stimuli, as reported for the heterologous expressed TRPV2 protein from mice that becomes more sensitive after repeated heat stimuli (Liu & Qin, ).…”