Elevated 18:0 lysophosphatidylcholine contributes to the development of pain in tissue injury

Dominic Anthony Friston, Joshua Cuddihy, Jessica Souza Luiz, An Hoai Truong, Laptin Ho, Meirvaan Basra, Peter Santha, Orsolya Oszlacs, Joao De Sousa Valente, Tim Marczylo, Sini Junttila, Helen Laycock, Declan Collins, Marcela Vizcaychipi, Attila Gyenesei, Zoltan Takats, Gabor Jancso, Elizabeth Want, Istvan Nagy*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

Abstract

Tissue injuries, including burns, are major causes of death and morbidity worldwide. These injuries result in the release of intracellular molecules and subsequent inflammatory reactions, changing the tissues' chemical milieu and leading to the development of persistent pain through activating pain-sensing primary sensory neurons. However, the majority of pain-inducing agents in injured tissues are unknown. Here, we report that, amongst other important metabolite changes, lysophosphatidylcholines (LPCs) including 18:0 LPC exhibit significant and consistent local burn injury-induced changes in concentration. 18:0 LPC induces immediate pain and the development of hypersensitivities to mechanical and heat stimuli through molecules including the transient receptor potential ion channel, vanilloid subfamily, member 1, and member 2 at least partly via increasing lateral pressure in the membrane. As levels of LPCs including 18:0 LPC increase in other tissue injuries, our data reveal a novel role for these lipids in injury-associated pain. These findings have high potential to improve patient care.

Original languageEnglish
Pages (from-to)E103-E115
JournalPain
Volume164
Issue number2
DOIs
Publication statusPublished - 1 Feb 2023
Externally publishedYes

Bibliographical note

Funding Information:
The work was supported by the National Centre for the Replacement, Refinement and Reduction of Animals in Research (D.A.F., I.N.), Chelsea and Westminster NHS Trust Charity (J.C., M.W., and I.N.) and The Wellcome Trust (H.L. and I.N.). The authors are grateful to Stephanie Wills and Mingxa Wang for their help in Ca imaging. The authors are grateful to Dr Laszlo Urban for his highly useful comments on this manuscript. 2+

Publisher Copyright:
© 2023 Lippincott Williams and Wilkins. All rights reserved.

Keywords

  • Heat hyperalgesia, Burn injury
  • Mechanical allodynia
  • Primary sensory neurons
  • TRPV1
  • TRPV2

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