Peripheral straightjacket (α2δ Ca2+ channel subunit) expression is required for neuropathic sensitization in Drosophila

Philos Trans R Soc Lond B Biol Sci. 2019 Nov 11;374(1785):20190287. doi: 10.1098/rstb.2019.0287. Epub 2019 Sep 23.

Abstract

Nerve injury leads to devastating and often untreatable neuropathic pain. While acute noxious sensation (nociception) is a crucial survival mechanism and is conserved across phyla, chronic neuropathic pain is considered a maladaptive response owing to its devastating impact on a patient's quality of life. We have recently shown that a neuropathic pain-like response occurs in adult Drosophila. However, the mechanisms underlying this phenomenon are largely unknown. Previous studies have shown that the α2δ peripheral calcium channel subunit straightjacket (stj) is a conserved factor required for thermal pain perception. We demonstrate here that stj is required in peripheral ppk+ sensory neurons for acute thermal responses and that it mediates nociceptive hypersensitivity in an adult Drosophila model of neuropathic pain-like disease. Given that calcium channels are the main targets of gabapentinoids (pregabalin and gabapentin), we assessed if these drugs can alleviate nociceptive hypersensitivity. Our findings suggest that gabapentinoids may prevent nociceptive hypersensitivity by preserving central inhibition after nerve injury. Together, our data further highlight the similarity of some mechanisms for pain-like conditions across phyla and validates the scientific use of Drosophila neuropathic sensitization models for analgesic drug discovery. This article is part of the Theo Murphy meeting issue 'Evolution of mechanisms and behaviour important for pain'.

Keywords: calcium channel; neuropathic sensitization; nociception.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Calcium Channels / genetics*
  • Calcium Channels / metabolism
  • Disease Models, Animal
  • Drosophila Proteins / genetics*
  • Drosophila Proteins / metabolism
  • Drosophila melanogaster / genetics
  • Drosophila melanogaster / physiology*
  • Gene Expression / physiology
  • Larva / genetics
  • Larva / physiology
  • Neuralgia / genetics*
  • Neuralgia / physiopathology

Substances

  • Calcium Channels
  • Drosophila Proteins
  • stj protein, Drosophila

Associated data

  • figshare/10.6084/m9.figshare.c.4626524