How do epithelial cells of the skin and colon communicate with sensory nerve fibers that transmit touch, temperature and pain?
Using optogenetic approaches, we discovered that activation of epithelial cells in the skin or the colon is sufficient to trigger pain reflexes in mice. These findings indicate that epithelial cells can communicate directly with nerve fibers to transmit stimuli and drive action potential firing. Current studies utilize molecular, cellular and optogenetic approaches, genetically engineered mouse models, calcium imaging and behavioral analysis to continue these studies and define how epithelial activation affects release of target-derived neuromodulators (e.g., ATP, transmitters) and activity of peripheral sensory neurons under homeostatic conditions and in response to injury or inflammation. In other studies in skin (carried out in collaboration with the Kaplan laboratory), and in the colon (carried out in collaboration with the Davis laboratory), we are investigating how sensory and autonomic activity affects immune cell activity and recruitment in the skin and colon.
Baumbauer KM, JJ DeBerry, PC Adelman, RM Miller, J Hachisuka, KH Lee, SE Ross, HR Koerber, BM Davis and KM Albers. 2015. Keratinocytes can modulate and directly initiate nociceptive responses. eLife; 4:e09674. DOI: 10.7554/eLife.09674. PMID: 26329459.
Najjar SA, BM Davis and KM Albers. 2020. Epithelial-neuronal communication: Implications for visceral pain signaling. Trends in Neurosciences. pii: S0166-2236(20)30001-1. doi: 10.1016/j.tins.2019.12.007. Review. PMID:31983457.
Zhang S, TN Edwards, VK Chaudhri, J Wu, JA Cohen, T Hirai, NR, EGS, PY Zhou, BD McNeil, YY, HR Koerber, TL Sumpter, AC Poholek, BM Davis, KM Albers, H Singh and D Kaplan. 2021. Nonpeptidergic neurons suppress mast cells via glutamate to maintain skin homeostasis. Cell. Apr 15;184(8):2151-2166.e16. doi: 10.1016/j.cell.2021.03.002. PMID: 33765440. https://www.ncbi.nlm.nih.gov/pubmed/33765440
Najjar SA, LL Ejoh, E Loeza-Alcocer, BS Edwards, KM Smith-Edwards, AY Epouhe, MS Gold, BM Davis and KM Albers. 2021. Optogenetic inhibition of colon epithelium reduces hypersensitivity in a mouse model of inflammatory bowel disease. PAIN 162:1126-1134. PMID: 33048854. https://www.ncbi.nlm.nih.gov/pubmed/33048854
Margiotta JF, KM Smith-Edwards, A Kolanoski, BM Davis, KM Albers and MJ Howard. 2021. Synaptic components, function and modulation characterized by GCaMP6f Ca2+ imaging in cholinergic myenteric ganglion neurons. Front Physiol 2021 Vol. 12 Pages 652714. Accession Number: 34408655 PMCID: PMC8365335 DOI: 10.3389/fphys.2021.652714. https://www.ncbi.nlm.nih.gov/pubmed/34408655
Najjar SA and KM Albers. 2021. Pain in IBD: Optogenetic strategies for study of neural-epithelial signaling. Crohn’s and Colitis 360 Volume 3, Issue 3, July 2021, otab040, https://doi.org/10.1093/crocol/otab040.
Epouhe A, M Ritter Jones, SA Najjar, JA Cohen, DH Kaplan, HR Koerber and KM Albers. 2022. Use of optogenetics for study of skin-nerve communication. In Contemporary approaches to the study of pain: from molecules to neural networks. Editor, R Seal. Springer Nature. Humana Press. DOI : 10.1007/978-1-0716-2039-7.