5: A Mouse Model of Post-Burn Pain and Itch with In Vivo Imaging of Trigeminal Neurons

Topic: Basic Science
Subtopic: Itch, Animal imaging (includes Ca2+ imaging, fluorescence microscopy), Behavioral studies

Background and Aims: Burn injury commonly leads to pain and persistent itch during wound healing, both of which markedly impair quality of life1-3. Despite their clinical significance, the underlying neural mechanisms of the neural processes that drive sensory dysfunction following burn injury remain poorly understood. This study seeks to develop a mouse model of post-burn pain and itch, and to investigate changes in primary sensory neuron activity using in vivo calcium imaging of trigeminal ganglion (TG) neurons.

Methods: Adult male C57BL/6J mice underwent unilateral cheek scald burn (4 mm, 8 s boiling water) or sham treatment. Wound area was quantified longitudinally by digital imaging. Scratching and wiping behaviors were recorded pre- and post-burn by blinded observers. Skin sections were processed for H&E or toluidine blue staining. For in vivo Ca²⁺ imaging, AAV-GCaMP was delivered to TG, and neuronal activity was recorded by confocal microscopy. Capsaicin and chloroquine were applied during recording. Data were analyzed using ANOVA with p < 0.05 considered significant.

Results: Following injury, mice exhibited both spontaneous pain-related behaviors (wiping) and itch-related behaviors (scratching). Pain-related behaviors peaked on day 1 and returned to baseline within 5 days, whereas itch-related behaviors peaked on day 7 and persisted for up to 28 days. In vivo calcium imaging revealed a significant increase in the number of TG neurons exhibiting spontaneous activity on days 1 and 7 post-injury compared to baseline. While the proportion of capsaicin-sensitive neurons remained unchanged after scald burn, the proportion of chloroquine-sensitive neurons was reduced on day 1 and partially recovered on day 7.

Conclusions: Enhanced spontaneous activity in primary sensory neurons may contribute to post-burn pain and itch. This model appears to be useful to investigate the neural mechanisms underlying sensory dysfunction following burn injury.

References: 1 Nedelec, B. & Carrougher, G. J. Pain and Pruritus Postburn Injury. J Burn Care Res 38, 142-145, doi:10.1097/BCR.0000000000000534 (2017).
2 Yosipovitch, G. & Hundley, J. L. Practical guidelines for relief of itch. Dermatol Nurs 16, 325-328; quiz 329 (2004).
3 Morgan, M. et al. Burn Pain: A Systematic and Critical Review of Epidemiology, Pathophysiology, and Treatment. Pain medicine 19, 708-734, doi:10.1093/pm/pnx228 (2018).

Presenting Author: Tasuku Akiyama
Submitting Author: Tasuku Akiyama

Senior Author: Tasuku Akiyama

IASP 2026 Global Year theme of Neuropathic Pain: No

• Hirotake Ishida: PhD - University of Miami Miller School of Medicine
• Darya Pavlenko: PhD - University of Miami Miller School of Medicine
• Kent Sakai: PhD - University of Miami Miller School of Medicine