How do epithelial cells of the skin communicate with sensory nerve fibers that transmit touch, temperature and pain?
Using optogenetic approaches, we discovered that activation of skin cells is sufficient to trigger pain reflexes in mice. These findings suggest that keratinocytes coomunicate directly to nerve fibers. However, the underlying mechanisms are not understood. Our work is aimed at understanding how keranocytes modulate the activity of primary sensory neurons in the skin. We are also interested in investigating whether this important communication between nerves and skin is altered when the skin is inflamed.
Keratinocytes can modulate and directly initiate nociceptive responses. Baumbauer, K.M., J.J. DeBerry, P.C. Adelman, R.H. Miller, J. Hachisuka, K.H. Lee, S.E. Ross, H.R. Koerber, B.M. Davis, and K.M. Albers. Elife, 2015; 4. Download Article
REGULATION OF NOCICEPTORS BY GROWTH FACTORS
How does inflammation cause the sensitization of nociceptors, and can we block this process to prevent pain?
Artemin is a growth factor that is commonly upregulated in inflammatory diseases such as pancreatitis, psoriasis, rheumatoid arthritis and cystitis. Moreover, we our work has revealed that Artemin causes profound changes to the function of sensory neurons, making them more sensitive to heat, cold and noxious chemicals. Our current work is aimed at understanding the underlying mechanisms through which artemin alters nociceptor function.
Artemin overexpression in skin enhances expression of TRPV1 and TRPA1 in cutaneous sensory neurons and leads to behavioral sensitivity to heat and cold. Elitt, C. M., S. L. McIlwrath, J. J. Lawson, S. A. Malin, D. C. Molliver, P. K. Cornuet, H. R. Koerber, B. M. Davis and K. M. Albers (2006). The Journal of neuroscience : the official journal of the Society for Neuroscience 26(33): 8578-8587. Download Article
TRPV1 and TRPA1 function and modulation are target tissue dependent. Malin, S., D. Molliver, J. A. Christianson, E. S. Schwartz, P. Cornuet, K. M. Albers and B. M. Davis (2011). The Journal of neuroscience : the official journal of the Society for Neuroscience 31(29): 10516-10528. Download Article
Artemin growth factor increases nicotinic cholinergic receptor subunit expression and activity in nociceptive sensory neurons. Albers, K. M., X. L. Zhang, C. M. Diges, E. S. Schwartz, C. I. Yang, B. M. Davis and M. S. Gold (2014). Molecular pain 10: 31. Download Article
Artemin Immunotherapy Is Effective in Preventing and Reversing Cystitis-Induced Bladder Hyperalgesia via TRPA1 Regulation. DeBerry, J. J., J. L. Saloman, B. K. Dragoo, K. M. Albers and B. M. Davis (2015). The journal of pain : official journal of the American Pain Society 16(7): 628-636. Download Article
TRANSCIRPTIONAL PROGRAMS OF PAIN
What are transcriptional pathways activated following inflammatory or neuropathic injury?
Another area of interest is how growth factor-mediated changes in signaling affects expression of ion channels involved in the perception and processing of pain signaling. A goal of this research is to identify novel transcriptional pathways activated following inflammatory or neuropathic injury in peripheral structures. One transcriptional regulator we identified as important for nerve growth and survival following injury is Sox11, a member of the Sry-type high mobility group (HMG) box family of transcription factors. Sox proteins are emerging as important transcriptional regulators best known for their key role in embryonic neuron development. The increased expression of Sox11 in adult neurons following injury suggests an important role in neuron plasticity and recovery as well. We are testing this role using RNAi treated cultured neurons combined with molecular level assays (microarray and luciferase assays, ChIPs) to identify transcriptional targets. By understanding how transcriptional signaling is regulated following nerve injury, we hope to improve our understanding of injury-associated changes in order to identify new therapeutic targets and better defined points of intervention.