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Citation
Khuong, T.M., Hamoudi, Z., Manion, J., Loo, L., Muralidharan, A., Neely, G.G. (2019). Peripheral straightjacket (α2δ Ca2+ channel subunit) expression is required for neuropathic sensitization in Drosophila.  Philos. Trans. R. Soc. Lond. B. Biol. Sci. 374(1785): 20190287.
FlyBase ID
FBrf0243529
Publication Type
Research paper
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'.

PubMed ID
PubMed Central ID
PMC6790392 (PMC) (EuropePMC)
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    Language of Publication
    English
    Additional Languages of Abstract
    Parent Publication
    Publication Type
    Journal
    Abbreviation
    Philos. Trans. R. Soc. Lond. B. Biol. Sci.
    Title
    Philosophical transactions of the Royal Society of London. Series B, Biological sciences
    Publication Year
    1887-
    ISBN/ISSN
    0962-8436 1471-2970
    Data From Reference
    Alleles (8)
    Genes (6)
    Insertions (2)
    Transgenic Constructs (5)