INTEGRATED APPROACH TO IDENTIFY NEW TARGETS FOR ANALGESICS FOR BURN INJURY-ASSOCIATED PAIN

Istvan Nagy

Imperial College London, London, UK

Abstract

Burn injury is associated with one of the most excruciating pain experiences. However, satisfactory relief of pain in burn injury is an unmet medical need. We have been using skin microdialysis in human models of burn injuries, and in an animal model of scalding type partial thickness burn injury followed by metabolomics, proteomics and lipidomics to describe burn injury induced alterations in the interstitial environment, which is pivotal for the initiation and maintenance of pain signalling in primary sensory neurons. In the animal model, we have also been using RNA sequencing of skin and dorsal root ganglia to respectively support chemical changes in the skin and burn injury-induced transcriptional changes in primary sensory neurons that contribute to enhanced activity and excitability of those neurons. In addition, we have started to analyse burn injury-induced changes in the chemistry of the skin in samples collected from burn-injured patients. Finally, in the animal model we have been studying changes in the spinal cord, which underlay the transcriptional changes hence the development of pain. We have already identified several metabolites, lipids and cytokimes/chemokines associated with burn injury. We have also identified alterations in gene expression both in the skin and dorsal root ganglia. We have shown that 18:0 lypophosphotidylcholine sensitises and activates a group of primary sensory neurons predominantly through the capsaicin receptor transient receptor potential cation channel subfamily V member 1 ion channel. Finally we have identified the first burn injury-induced epigenetic tag in spinal dorsal horn neurons and showed that blocking the enzyme producing that tag results in the failure of heat hyperalgesia to develop.