Drosophila in Pain Research

Drosophila has been used as a model organism for conventional neuroscience research on pain perception and human disease mechanisms. Relying on the complexity of Drosophila pain physiological behavior and the relatively simple structure of the peripheral and central nervous system, it is used by scientists to identify and study the genes, neurons and circuits underlying basic pain perception and modulation. CD BioSciences is committed to advancing the research progress of Drosophila in pain biology and disorders, and we look forward to collaborating with you in the future.

Background of Pain and Related Diseases

Nociception is an important and conserved protective mechanism in postnatal animals, critical for responding to acute detection of noxious stimuli. Pain/injury perception is a complex whole-body physiological process. In vertebrates and Drosophila, these action potentials can either be transmitted directly to spinal motor neurons to stimulate escape behavior (so-called monosynaptic reflexes) or propagated through spinal cord interneurons to higher processing centers in the brain. In this way a new discipline, the biology of nociception, was developed.

However, in addition to being a useful protective mechanism, pain may also be a common chronic disease in humans. The prevalence of chronic or persistent pain in the population has been estimated at 34-53%. More importantly, it may lead to the development of cognitive impairment and psychological disorders. To date, medicine has largely taken a reactive approach to chronic pain rather than a proactive or preventive one. In addition, treatment relies on the long-term use of analgesics, with the potential for serious sequelae and addictions. Therefore, the exploration of the molecular pathogenesis and genetics of chronic pain disorders may facilitate precise pain diagnosis and treatment in the future.

Application of Drosophila in Pain Research

The type II peripheral sensory neurons of flies are the primary injury sensory neurons, which are structurally similar to mammalian. Using Drosophila adults and larvae as models for studying cold, heat and mechanical injury sensation and in vivo analgesia research, scientists have developed dozens of different models for chronic and neuropathic pain research and screening at the cellular level and globally, not only reducing the difficulty of screening but also discovering numerous new targets and signaling pathways related to nociception.

Studying Molecular Targets of Pain

Around 2005, scientists identified for the first time the gene associated with nociception in Drosophila, painless, a member of TRPA1 subfamily (TRP, temperature-responsive voltage-gated cation channels). After validation, the TRPA1 pathway has been identified as a potential therapeutic target for inflammatory pain and neuropathic pain. In addition, multiple mammalian pain homologs from Drosophila were identified, such as the amiloride-sensitive cation channel Accn3, the GDNF family receptor alpha2, and the protein kinase G (promotes thermal sensitization in response to inflammation), demonstrating the viability of Drosophila as a new animal model of in vivo nociception.

Studying Pain Signaling Pathways

The Drosophila large-scale screening advantage is further amplified in the field of resolving the conserved genetics of injury perception, chronic pain, and conserved regulatory networks of neurons. Through genome-wide functional assessment, hundreds of putative injury sensing genes and conserved pathways with previously unknown were identified in Drosophila, including ubiquitin-mediated protein hydrolysis pathways, hedgehog (the first pathway involved in pain sensation formation validated in Drosophila), Wnt (involved in neuropathic pain onset), ErbB, JAK-Stat, Notch, mTOR, TGF-β and Ca²⁺ signaling pathways. The rapid genetic screening platform in Drosophila helps to study the mechanisms of acute injury perception and neurological damage.

Application on Pain Management and Diagnosis

Adult Drosophila have been shown to have a chronic sensitizing profile, similar to vertebrates. Signaling pathways include, tumor necrosis factor alpha (TNF-α), Hedgehog (Hh), tachykinin (Tk), and bone morphogenetic protein (BMP). These studies and data reveal the potential of Drosophila to develop targeted approaches to chronic pain management, including identifying populations at risk for chronic pain, and providing treatments for prevention. The discovery of new conservative targets and local pain studies could reduce the short-term intake of vast sedative drugs, and also avoid systemic opioid abuse.

Fig.1 A Comparison of the Genetic Investigation and Functional Analysis of Neuropathic Pain in Human and Animal Models (Calvo et al. 2019)

CD BioSciences has decades of experience in Drosophila neuroscience. We are able to provide comprehensive scientific services for pain genesis and disease mechanisms to clients worldwide. Please contact us to discuss your project and create a custom quote.

References

Milinkeviciute G, et al. (2012). Drosophila as a tool for studying the conserved genetics of pain. Clinical genetics, 82(4), 359-366.
Im SH, et al. (2012). Pokes, sunburn, and hot sauce: Drosophila as an emerging model for the biology of nociception. Developmental Dynamics, 241(1), 16-26.
Calvo M, et al. (2019). The Genetics of Neuropathic Pain from Model Organisms to Clinical Application. Neuron, 104(4), 637–653.
McParland A, et al. (2021). The brinker repressor system regulates injury-induced nociceptive sensitization in Drosophila melanogaster. Molecular Pain, 17, 17448069211037401.

For research use only. Not intended for any clinical use.

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